Pub Date : 2014-01-01DOI: 10.3844/AJPTSP.2014.13.23
I. Bin-Jaliah, Samah Elattar, E. F. Khaleel, L. El-Sayed, M. Haidara
It was shown that hyperglycemia in diabetic patient s is the main factor of diabetic peripheral neuropathies. Various pathways related to oxidative stress, vascular defect and defective endothelium dependent relaxation have been implicated in the de velopment of diabetic peripheral neuropathy. A substantial number of studies have shown that antio xidant treatment are promising therapeutics that ca n prevent or correct reduced motor nerve conduction i n diabetic rats by acting on these mechanisms. This study was designed to investigate the possible role of insulin treatment along with or without vitamin E or L-arginine on diabetic neuropathy. This goal was accessed by examining nerve conduction, parameters of oxidative stress and lipid peroxidation as well as the expression level of endothelial nitric oxide synthase in the sciatic nerve of control and strept ozotocine-induced diabetic rats. Data showed that diabetic rats showed increased levels of serum gluc ose (382.5%) and sciatic nerve lipid peroxidation Marker (MDA, 261.6%) with a concomitant decrease in the expression of sciatic nerve eNOS mRNA as compared to control rats. The nerve conduction stud ies of the sciatic nerves of these rats showed decr ease conduction as evident by delayed NCV (63.6%) and low Amplitude of Muscle Contraction (AMC, 36.4%). Solitary insulin treatment (but not vitamin -E or L-arginine) corrected serum glucose to contro l values and corrected nerve conduction parameters in the sciatic nerve. However, treating diabetic rats with different doses of vitamin E (300 mg kg -1 and 600 mg kg -1 ) significantly reduced oxidative stress by decreasing MDA and increasing GPx activity, corrected NCV by reducing the latency and improving AMC and increased eNOS mRNA expression in sciatic nerve with a more profound effect to seen with the high dose (600 mg kg -1 ). However, the maximum potent ameliorating effect of the vitamin E on these parameters was seen when administered in combination with insulin. On the other hand, L-arginine treatment alone or in combination with insulin had no effect on the oxidative stress markers nor eNOS expression but significantly and maximally improved NCV through reducing the conduction latency and increasing AMC. This study supported the notion tha t diabetic peripheral neuropathy is a multifactoria l complication, caused by hyperglycemia, oxidative st ress and vascular impairment. It is concluded that conjugate treatment with vitamin-E, especially in h igher doses, with insulin could be of great value. Moreover correction of impaired nerve blood flow by drugs that induce nitric oxide has proved to be efficient in the protection against and correction of experimental diabetic peripheral neuropathy.
结果表明，糖尿病患者的高血糖是糖尿病周围神经病变的主要因素。与氧化应激、血管缺损和内皮依赖性松弛缺陷相关的多种途径与糖尿病周围神经病变的发展有关。大量研究表明，抗氧化治疗是一种很有前景的治疗方法，可以通过作用于这些机制来预防或纠正糖尿病大鼠运动神经传导减少。本研究旨在探讨胰岛素治疗联合或不联合维生素E或l -精氨酸治疗糖尿病神经病变的可能作用。通过检测神经传导、氧化应激和脂质过氧化参数以及内皮型一氧化氮合酶在对照组和链球菌苯佐辛诱导的糖尿病大鼠坐骨神经中的表达水平，达到这一目的。数据显示，与对照大鼠相比，糖尿病大鼠血清葡萄糖(382.5%)和坐骨神经脂质过氧化标志物(MDA, 261.6%)水平升高，同时坐骨神经eNOS mRNA表达降低。神经传导研究显示，大鼠坐骨神经传导减弱，表现为NCV延迟(63.6%)和肌肉收缩幅度低(AMC, 36.4%)。单独胰岛素治疗(但不包括维生素e或l -精氨酸)可纠正血清葡萄糖以控制l值，并纠正坐骨神经的神经传导参数。然而，不同剂量维生素E (300 mg kg -1和600 mg kg -1)处理糖尿病大鼠，通过降低MDA和增加GPx活性显著降低氧化应激，通过减少潜伏期和改善AMC纠正NCV，增加坐骨神经eNOS mRNA表达，且效果比高剂量(600 mg kg -1)更深远。然而，当与胰岛素联合使用时，维生素E对这些参数的最大有效改善效果被看到。另一方面，l -精氨酸单独或联合胰岛素治疗对氧化应激标志物和eNOS表达均无影响，但通过减少传导潜伏期和增加AMC显著且最大限度地改善了NCV。该研究支持了糖尿病周围神经病变是由高血糖、氧化应激和血管损伤引起的多因素并发症的观点。综上所述，维生素e与胰岛素结合治疗，特别是在高剂量下，可能具有很大的价值。此外，通过诱导一氧化氮的药物来纠正受损的神经血流已被证明对实验性糖尿病周围神经病变的保护和纠正是有效的。
{"title":"REMEDIAL EFFECTS OF VITAMIN E AND L-ARGININE ON PERIPHERAL NEUROPATHY IN STREPTOZOTOCIN-INDUCED DIABETIC RATS","authors":"I. Bin-Jaliah, Samah Elattar, E. F. Khaleel, L. El-Sayed, M. Haidara","doi":"10.3844/AJPTSP.2014.13.23","DOIUrl":"https://doi.org/10.3844/AJPTSP.2014.13.23","url":null,"abstract":"It was shown that hyperglycemia in diabetic patient s is the main factor of diabetic peripheral neuropathies. Various pathways related to oxidative stress, vascular defect and defective endothelium dependent relaxation have been implicated in the de velopment of diabetic peripheral neuropathy. A substantial number of studies have shown that antio xidant treatment are promising therapeutics that ca n prevent or correct reduced motor nerve conduction i n diabetic rats by acting on these mechanisms. This study was designed to investigate the possible role of insulin treatment along with or without vitamin E or L-arginine on diabetic neuropathy. This goal was accessed by examining nerve conduction, parameters of oxidative stress and lipid peroxidation as well as the expression level of endothelial nitric oxide synthase in the sciatic nerve of control and strept ozotocine-induced diabetic rats. Data showed that diabetic rats showed increased levels of serum gluc ose (382.5%) and sciatic nerve lipid peroxidation Marker (MDA, 261.6%) with a concomitant decrease in the expression of sciatic nerve eNOS mRNA as compared to control rats. The nerve conduction stud ies of the sciatic nerves of these rats showed decr ease conduction as evident by delayed NCV (63.6%) and low Amplitude of Muscle Contraction (AMC, 36.4%). Solitary insulin treatment (but not vitamin -E or L-arginine) corrected serum glucose to contro l values and corrected nerve conduction parameters in the sciatic nerve. However, treating diabetic rats with different doses of vitamin E (300 mg kg -1 and 600 mg kg -1 ) significantly reduced oxidative stress by decreasing MDA and increasing GPx activity, corrected NCV by reducing the latency and improving AMC and increased eNOS mRNA expression in sciatic nerve with a more profound effect to seen with the high dose (600 mg kg -1 ). However, the maximum potent ameliorating effect of the vitamin E on these parameters was seen when administered in combination with insulin. On the other hand, L-arginine treatment alone or in combination with insulin had no effect on the oxidative stress markers nor eNOS expression but significantly and maximally improved NCV through reducing the conduction latency and increasing AMC. This study supported the notion tha t diabetic peripheral neuropathy is a multifactoria l complication, caused by hyperglycemia, oxidative st ress and vascular impairment. It is concluded that conjugate treatment with vitamin-E, especially in h igher doses, with insulin could be of great value. Moreover correction of impaired nerve blood flow by drugs that induce nitric oxide has proved to be efficient in the protection against and correction of experimental diabetic peripheral neuropathy.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"83 6 1","pages":"13-23"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87654621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-01-01DOI: 10.3844/ajptsp.2014.24.28
M. A. Wijayanti
A series of studies has been conducted to prove the Eurycoma longifolia Jack. root as an antimalarial. However, the in vivo antiplasmodial activity of E. longifolia Jack. root standardized extract and its lethal dos e 50% (LD50) values is unknown. In vivo antiplasmodial activity was conducted on Plasmodium berghei infected Swiss mice as malaria model with 4-day suppression methods. Sixty mice were divided into 6 gr oups. Five groups as treatment groups received test mater ial with 5 various doses and one group was given di stilled water as control group. Parasite growth inhibition was calculated by comparing the parasitemia at trea tment groups to control group. Effective dose that could inhibit parasite growth by 50% (ED50) was calculated by probit analysis based on the relationship between d ose and the percentage of parasite growth inhibitio n. The results showed that E. longifolia Jack. root standardized extract have in vivo antiplasmodial activity in P. berghei infected Swiss mice with ED50 value of 28.78 mg kg -1 . Acute toxicity testing was conducted on 60 mice, divided into 6 groups. Five groups received t est materials with 5 various doses as a single dose orally. One other group was given distilled water as contro l group. Each animal was observed for the first 24 h and observation was continued for 14 days. The lethal d ose 50% (LD50) was calculated by probit analysis based on the number of animal deaths that occurred within 24 h after the administration of the test material . The results showed that the LD50 value of E. longifolia Jack. root standardized extract was 6128.71 mg kg -1 . Therapeutic Index was calculated as ratio of the LD 50 and ED50 with results 212.95. It showed high therapeutic index which indicated that E. longifolia Jack. root standardized extract has low toxicity.
已经进行了一系列的研究来证明长叶Eurycoma longifolia Jack。根作为抗疟药。然而，金针叶的体内抗疟原虫活性并没有明显的变化。根茎标准化提取物及其致死剂量50% (LD50)值未知。采用4 d抑制法对感染伯氏疟原虫的瑞士小鼠进行体内抗疟原虫活性研究。60只小鼠分为6组。5组作为治疗组给予5种不同剂量的试验物质，1组给予静水作为对照组。通过比较治疗组和对照组的寄生率计算寄生虫生长抑制率。根据d值与寄生虫生长抑制率的关系，采用概率分析法计算出抑制50%寄生虫生长的有效剂量(ED50)。根标准化提取物对伯氏线虫感染的瑞士小鼠具有体内抗疟原虫活性，ED50值为28.78 mg kg -1。将60只小鼠分为6组进行急性毒性试验。5组分别口服5种不同剂量的试验材料。另一组给予蒸馏水作为对照组。每只动物观察24 h，连续观察14 d。根据给药后24 h内动物死亡数，采用概率分析法计算致死剂量50% (LD50)。结果表明，金针叶的LD50值;根标准提取物6128.71 mg kg -1。以ld50与ED50之比计算治疗指数，结果为212.95。结果表明，该方法具有较高的治疗指标。根茎标准化提取物毒性低。
{"title":"IN VIVO ANTIPLASMODIAL ACTIVITY AND ACUTE TOXICITY OF STANDARDIZED EXTRACT OF EURYCOMA LONGIFOLIA JACK. ROOT TRADITIONALLY USED TO TREAT MALARIA","authors":"M. A. Wijayanti","doi":"10.3844/ajptsp.2014.24.28","DOIUrl":"https://doi.org/10.3844/ajptsp.2014.24.28","url":null,"abstract":"A series of studies has been conducted to prove the Eurycoma longifolia Jack. root as an antimalarial. However, the in vivo antiplasmodial activity of E. longifolia Jack. root standardized extract and its lethal dos e 50% (LD50) values is unknown. In vivo antiplasmodial activity was conducted on Plasmodium berghei infected Swiss mice as malaria model with 4-day suppression methods. Sixty mice were divided into 6 gr oups. Five groups as treatment groups received test mater ial with 5 various doses and one group was given di stilled water as control group. Parasite growth inhibition was calculated by comparing the parasitemia at trea tment groups to control group. Effective dose that could inhibit parasite growth by 50% (ED50) was calculated by probit analysis based on the relationship between d ose and the percentage of parasite growth inhibitio n. The results showed that E. longifolia Jack. root standardized extract have in vivo antiplasmodial activity in P. berghei infected Swiss mice with ED50 value of 28.78 mg kg -1 . Acute toxicity testing was conducted on 60 mice, divided into 6 groups. Five groups received t est materials with 5 various doses as a single dose orally. One other group was given distilled water as contro l group. Each animal was observed for the first 24 h and observation was continued for 14 days. The lethal d ose 50% (LD50) was calculated by probit analysis based on the number of animal deaths that occurred within 24 h after the administration of the test material . The results showed that the LD50 value of E. longifolia Jack. root standardized extract was 6128.71 mg kg -1 . Therapeutic Index was calculated as ratio of the LD 50 and ED50 with results 212.95. It showed high therapeutic index which indicated that E. longifolia Jack. root standardized extract has low toxicity.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"8 1","pages":"24-28"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86472630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-01-01DOI: 10.3844/AJPTSP.2014.29.38
A. El-kirdasy, M. Nassan, A. Baiomy, T. Ismail, M. Soliman, H. Attia, S. Arabia
In this study, we examined the ameliorative action of N-Acetylcysteine (NAC) against Titanium Dioxide (TiO2) induced testicular degeneration in albino ra ts. Adult male albino rats were given saline as a control group, TiO2 (1200 mg kg -1 BW), NAC (100 mg kg -1 BW) and co-treatment of NAC and TiO2 as a protective group for 3 months. Testicular tissues were extracted for changes in testicular gene expression and histopathology. Administration of Ti O2 significantly increased mRNA expression of IL-6 and TNF-α that are normalized by NAC administration. TiO2 ad ministration down regulated Glutathione-S-Transferase (GST) while increased B-cell Lymphoma2 (BcL2) expressions. Coadministration of rats by NAC together with TiO2 no rmalized changes in GST and BcL2 expression. Expression of steroidogenesis related genes [Androg en Binding Protein (ABR), 17 β-Hydroxysteroid Dehydrogenase (17 β-HSD), cytochrome P450 17A (CYP 17α ) and aromatase] showed down regulation in TiO2 administered groups and normalized when NAC given together with TiO2. Moreover, TiO2 induced toxicity in testes that accompanied by dege neration in seminiferous tubules with congestion, oedema and cell disruption that are partially norma lized by co-administration of NAC with TiO2. In conclusion, the present findings confirmed the benf icial effect of NAC to prevent apoptosis in spermatogenic and sertoli cells and testicular dysf unction induced by TiO2 in male albino rats.
研究了n -乙酰半胱氨酸(NAC)对二氧化钛(TiO2)诱导的白化病大鼠睾丸变性的改善作用。以成年雄性白化病大鼠为对照组，分别给予二氧化钛(TiO2) (1200 mg kg -1 BW)、NAC (100 mg kg -1 BW)和NAC (NAC和TiO2共处理3个月作为保护组。提取睾丸组织，观察睾丸基因表达和组织病理学变化。tio2处理显著增加NAC处理后正常表达的IL-6和TNF-α mRNA的表达。TiO2和给药可下调谷胱甘肽- s -转移酶(GST)，同时增加b细胞淋巴瘤2 (BcL2)的表达。NAC与TiO2共给药大鼠GST和BcL2表达无明显变化。甾体生成相关基因[雄激素结合蛋白(ABR)、17 β-羟基类固醇脱氢酶(17 β-HSD)、细胞色素P450 17A (CYP 17α)和芳香化酶]在TiO2给药组表达下调，NAC与TiO2一起给药组表达正常化。此外，TiO2在睾丸中诱导毒性，并伴有精管充血、水肿和细胞破坏，这些在NAC和TiO2共同给药后部分正常化。综上所述，本研究结果证实了NAC对雄性白化大鼠生精细胞和支持细胞凋亡及TiO2诱导的睾丸功能障碍的有益作用。
{"title":"POTENTIAL AMELIORATIVE ROLE OF N-ACETYLCYSTEINE AGAINST TESTICULAR DYSFUNCTION INDUCED BY TITANIUM DIOXIDE IN MALE ALBINO RATS","authors":"A. El-kirdasy, M. Nassan, A. Baiomy, T. Ismail, M. Soliman, H. Attia, S. Arabia","doi":"10.3844/AJPTSP.2014.29.38","DOIUrl":"https://doi.org/10.3844/AJPTSP.2014.29.38","url":null,"abstract":"In this study, we examined the ameliorative action of N-Acetylcysteine (NAC) against Titanium Dioxide (TiO2) induced testicular degeneration in albino ra ts. Adult male albino rats were given saline as a control group, TiO2 (1200 mg kg -1 BW), NAC (100 mg kg -1 BW) and co-treatment of NAC and TiO2 as a protective group for 3 months. Testicular tissues were extracted for changes in testicular gene expression and histopathology. Administration of Ti O2 significantly increased mRNA expression of IL-6 and TNF-α that are normalized by NAC administration. TiO2 ad ministration down regulated Glutathione-S-Transferase (GST) while increased B-cell Lymphoma2 (BcL2) expressions. Coadministration of rats by NAC together with TiO2 no rmalized changes in GST and BcL2 expression. Expression of steroidogenesis related genes [Androg en Binding Protein (ABR), 17 β-Hydroxysteroid Dehydrogenase (17 β-HSD), cytochrome P450 17A (CYP 17α ) and aromatase] showed down regulation in TiO2 administered groups and normalized when NAC given together with TiO2. Moreover, TiO2 induced toxicity in testes that accompanied by dege neration in seminiferous tubules with congestion, oedema and cell disruption that are partially norma lized by co-administration of NAC with TiO2. In conclusion, the present findings confirmed the benf icial effect of NAC to prevent apoptosis in spermatogenic and sertoli cells and testicular dysf unction induced by TiO2 in male albino rats.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"2005 1","pages":"29-38"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78876516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-01-01DOI: 10.3844/AJPTSP.2014.1.12
Hassan M Al-Musa, F. Al-Hashem
This study was undertaken to evaluate the hypoglyce mic and hepatorenal protective effect of ethanolic extract of Chamomile recutita flowers in streptozotocin-Diabetic Rats. Before the beginning of the experiments, a cute and subacute studies were carried out in control an imals first to investigate the LD50 of this extract . In the experimental design, adult male albino rats were di vided into five groups: (1) normal control, (2) con trol + extract, (3) diabetic control, (4) diabetic+extract and (5) diabetic+glibenclamide (200 �g kg -1 ). The extract was given to the desired groups at a final dose of 500 mg kg -1 and all treatments were administered orally for 4 weeks on daily basis. Serum glucose, insulin, activ ities of serum marker enzymes of liver function as well as markers of kidney function was measured. The oxidative stress was assessed by measuring lipid peroxida tion (TBARS) and enzyme activities of Glutathione Peroxidase (GPx) superoxide dismutase in both liver and kidney homogenates. The data showed that ethanolic flower extract of Chamomile recutita demonstrated high safety margin since the animals tolerated up to 100 00 mg kg -1 body weight of the extract orally in the acute toxicity study and tolerated repeated doses up to 5 00 mg kg -1 for 28 days. Administration of the extract to control and diabetic rats caused significant decrea se in glucose level in serum without improving insu lin levels and resulted in significant increases in SOD and GP x activities with a parallel decrease in lipid pero xidation (TBARS levels) in the livers and kidneys. Furthermore, in diabetic rats, treatment with the extract re sulted in significant decreases in the serum activities of li ver enzymes including AST, ALT and ALP and in the levels of urea and creatinine. The hepatoprotective effect of the extract were confirmed by histological impr ovements in hepatic and renal tissue of the diabetic treated rats. However, the effect of the extract in diabet ic rats was comparable to glibenclamide. This study demonstrates that Chamomile recutita flowers ethanolic extract has potent hypoglycemic, antioxidant and hepatorenal pr otective effects in diabetic rats.
本研究旨在探讨洋甘菊花乙醇提取物对链脲佐菌素糖尿病大鼠的降糖和肝肾保护作用。在实验开始前，先在对照组和动物中进行了急性和亚急性实验，研究了该提取物的LD50。实验设计将成年雄性白化大鼠分为5组:(1)正常对照组，(2)对照组+提取物组，(3)糖尿病对照组，(4)糖尿病+提取物组，(5)糖尿病+格列本脲组(200 μ g kg -1)。最终给药剂量为500 mg kg -1，所有治疗均每日口服4周。测定血清葡萄糖、胰岛素、肝功能指标酶活性及肾功能指标。通过测定肝脏和肾脏匀浆的脂质过氧化(TBARS)和谷胱甘肽过氧化物酶(GPx)超氧化物歧化酶活性来评估氧化应激。数据显示，洋甘菊乙醇花提取物具有较高的安全边际，因为在急性毒性研究中，动物口服高达1000mg kg -1体重的提取物，并耐受高达500mg kg -1 28天的重复剂量。对照大鼠和糖尿病大鼠服用该提取物后，血清葡萄糖水平显著降低，但胰岛素水平没有改善，SOD和GP x活性显著升高，肝脏和肾脏的脂质过氧化(TBARS)水平同时降低。此外，在糖尿病大鼠中，用提取物处理导致血清中包括AST、ALT和ALP在内的肝酶活性以及尿素和肌酐水平显著降低。通过对糖尿病大鼠肝脏和肾脏组织的组织学改善，证实了该提取物的保肝作用。然而，提取物对糖尿病大鼠的作用与格列本脲相当。本研究表明，洋甘菊醇提物对糖尿病大鼠具有较强的降血糖、抗氧化和肝肾保护作用。
{"title":"HYPOGLYCEMIC, HEPATO-RENAL AND ANTIOXIDANT POTENTIAL EFFECTS OF CHAMOMILE RECUTITA FLOWERS ETHANOLIC EXTRACT IN STREPTOZOTOCIN-DIABETIC RATS","authors":"Hassan M Al-Musa, F. Al-Hashem","doi":"10.3844/AJPTSP.2014.1.12","DOIUrl":"https://doi.org/10.3844/AJPTSP.2014.1.12","url":null,"abstract":"This study was undertaken to evaluate the hypoglyce mic and hepatorenal protective effect of ethanolic extract of Chamomile recutita flowers in streptozotocin-Diabetic Rats. Before the beginning of the experiments, a cute and subacute studies were carried out in control an imals first to investigate the LD50 of this extract . In the experimental design, adult male albino rats were di vided into five groups: (1) normal control, (2) con trol + extract, (3) diabetic control, (4) diabetic+extract and (5) diabetic+glibenclamide (200 �g kg -1 ). The extract was given to the desired groups at a final dose of 500 mg kg -1 and all treatments were administered orally for 4 weeks on daily basis. Serum glucose, insulin, activ ities of serum marker enzymes of liver function as well as markers of kidney function was measured. The oxidative stress was assessed by measuring lipid peroxida tion (TBARS) and enzyme activities of Glutathione Peroxidase (GPx) superoxide dismutase in both liver and kidney homogenates. The data showed that ethanolic flower extract of Chamomile recutita demonstrated high safety margin since the animals tolerated up to 100 00 mg kg -1 body weight of the extract orally in the acute toxicity study and tolerated repeated doses up to 5 00 mg kg -1 for 28 days. Administration of the extract to control and diabetic rats caused significant decrea se in glucose level in serum without improving insu lin levels and resulted in significant increases in SOD and GP x activities with a parallel decrease in lipid pero xidation (TBARS levels) in the livers and kidneys. Furthermore, in diabetic rats, treatment with the extract re sulted in significant decreases in the serum activities of li ver enzymes including AST, ALT and ALP and in the levels of urea and creatinine. The hepatoprotective effect of the extract were confirmed by histological impr ovements in hepatic and renal tissue of the diabetic treated rats. However, the effect of the extract in diabet ic rats was comparable to glibenclamide. This study demonstrates that Chamomile recutita flowers ethanolic extract has potent hypoglycemic, antioxidant and hepatorenal pr otective effects in diabetic rats.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"12 1","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75133650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-12-03DOI: 10.3844/AJPTSP.2013.209.217
I. Saleh, Z. Ali, F. Hamada, M. Abd-Ellah, L. Walker, I. Khan, M. Ashfaq
The concern about safety of consumption of Green Tea (GT) supplements has become a scope of many studies. We and others have described earlier the effect of the administration of GT and its polyphenols on liver in a mouse model. In this study we aimed to investigate the effect of GT on HepG2 cells. HepG2 cells were treated with different concentrations of GT with and without presensitization with Lipopolysaccharide (LPS). The viability of cells did not change at low and moderate concentrations of GT, while at very high concentration; GT caused the viability of the cells to decrease. A decrease in the viability of presensitized cells was observed after exposure to moderate and high doses of GT. Also, OX.LDL, CXCL16, TNF α, TGF β, RAR and RXR were found to be over-expressed in these cells, while this over-expression was not observed in the cells upon treatment with GT without LPS or upon treatment with LPS alone. These results indicate that GT even at high doses does not cause oxidative stress. However, under inflammatory stress conditions it may cause oxidative stress which in turn may lead to liver toxicity.
{"title":"Effect of Green Tea on Hepatic Cells Under the Influence of Inflammatory Conditions: In Vitro Study","authors":"I. Saleh, Z. Ali, F. Hamada, M. Abd-Ellah, L. Walker, I. Khan, M. Ashfaq","doi":"10.3844/AJPTSP.2013.209.217","DOIUrl":"https://doi.org/10.3844/AJPTSP.2013.209.217","url":null,"abstract":"The concern about safety of consumption of Green Tea (GT) supplements has become a scope of many studies. We and others have described earlier the effect of the administration of GT and its polyphenols on liver in a mouse model. In this study we aimed to investigate the effect of GT on HepG2 cells. HepG2 cells were treated with different concentrations of GT with and without presensitization with Lipopolysaccharide (LPS). The viability of cells did not change at low and moderate concentrations of GT, while at very high concentration; GT caused the viability of the cells to decrease. A decrease in the viability of presensitized cells was observed after exposure to moderate and high doses of GT. Also, OX.LDL, CXCL16, TNF α, TGF β, RAR and RXR were found to be over-expressed in these cells, while this over-expression was not observed in the cells upon treatment with GT without LPS or upon treatment with LPS alone. These results indicate that GT even at high doses does not cause oxidative stress. However, under inflammatory stress conditions it may cause oxidative stress which in turn may lead to liver toxicity.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"62 1","pages":"209-217"},"PeriodicalIF":0.0,"publicationDate":"2013-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89489702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-11-23DOI: 10.3844/AJPTSP.2013.197.208
T. Ismail, M. Soliman, S. Ismail
Adiponectin is a protein synthesized from adipose tissue, increases peripheral glucose utilization in liver and skeletal muscle. Adiponectin expression and secretion are decreased during obesity and insulin resistance. In this study, the effect of insulin, metformin and dexamethasone on serum lipid profiles was examined in Type 2 Diabetic (T2D) rats. T2D was induced by feeding rats a high fat diet for 4 weeks plus medium dose of Streptozotocin (STZ, 35 mk kg-1 BW). Adiponectin, adiponectin receptors (AdipoR-1 and AdipoR-2), leptin, Peroxisome Prolifrator Activated Receptor gamma (PPAR-γ), Hormone Sensitive Lipase (HSL), Pyruvate Kinase (PK), enolase and Glucose Trasporter-2 (GLUT-2) expression in epididymal adipose and liver tissue were examined using RT-PCR. Results showed that metformin improved insulin resistance by normalizing serum lipid profiles in diabetic rats, while dexamethasone did not alter it. Metformin up-regulated adiponectin, AdipoR-1 and AdipoR-2 expression, while insulin and dexamethasone down-regulated them. Leptin expression was decreased while PPARγ, HSL, PK, enolase and GLUT-2 expression was increased by metformin administration. Dexamethasone failed to improve insulin resistance in T2D rats. In conclusion, metformin ameliorates T2D through controlling adiponectin expression and its consequent genes of lipids and glucose metabolism.
{"title":"Adiponectin Regulation in Type 2 Diabetic Rats: Effects of Insulin, Metformin and Dexamethasone","authors":"T. Ismail, M. Soliman, S. Ismail","doi":"10.3844/AJPTSP.2013.197.208","DOIUrl":"https://doi.org/10.3844/AJPTSP.2013.197.208","url":null,"abstract":"Adiponectin is a protein synthesized from adipose tissue, increases peripheral glucose utilization in liver and skeletal muscle. Adiponectin expression and secretion are decreased during obesity and insulin resistance. In this study, the effect of insulin, metformin and dexamethasone on serum lipid profiles was examined in Type 2 Diabetic (T2D) rats. T2D was induced by feeding rats a high fat diet for 4 weeks plus medium dose of Streptozotocin (STZ, 35 mk kg-1 BW). Adiponectin, adiponectin receptors (AdipoR-1 and AdipoR-2), leptin, Peroxisome Prolifrator Activated Receptor gamma (PPAR-γ), Hormone Sensitive Lipase (HSL), Pyruvate Kinase (PK), enolase and Glucose Trasporter-2 (GLUT-2) expression in epididymal adipose and liver tissue were examined using RT-PCR. Results showed that metformin improved insulin resistance by normalizing serum lipid profiles in diabetic rats, while dexamethasone did not alter it. Metformin up-regulated adiponectin, AdipoR-1 and AdipoR-2 expression, while insulin and dexamethasone down-regulated them. Leptin expression was decreased while PPARγ, HSL, PK, enolase and GLUT-2 expression was increased by metformin administration. Dexamethasone failed to improve insulin resistance in T2D rats. In conclusion, metformin ameliorates T2D through controlling adiponectin expression and its consequent genes of lipids and glucose metabolism.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"25 1","pages":"197-208"},"PeriodicalIF":0.0,"publicationDate":"2013-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84191564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-11-20DOI: 10.3844/AJPTSP.2013.187.196
A. Elias, B. Nelson, Deo Oputiri, Oru-Bo Precious Geoffrey
Antiretroviral drugs are used for the treatment of human immunodeficiency virus, they are used as combination regimens to achieve the highest possibl e benefit, tolerability, compliance and to diminish the risk of resistance development. Reports from precli nical and clinical studies have linked antiretrovir als with some toxicological effects which could be associate d with redox imbalance (oxidative stress). This stimulated us to review relevant literature on the relationship between antiretroviral induced toxicol ogical effects and redox imbalance. Available literature o n antiretroviral associated toxicological effects a nd oxidative stress were comprehensively reviewed. Lit erature showed that antiretrovirals are associated with toxicological effects which includes hepatotox icity, cardiotoxicity, hematotoxicity and nephrotoxicity. Reports in animal studies also show ed that these toxicological effects could be associated with oxidative stress through the genera tion of oxidative radicals, depletion of antioxidan ts and antioxidant enzymes leading to mitochondria damage in the heart, kidney, liver brain and other organs. In humans, studies also showed that antiret rovirals are associated with lipid peroxidation, depletion of antoxidants and antioxidant enzymes wh ich are elements of oxidative stress. Furthermore it was observed that supplementations with some ant ioxidants mitigated antiretroviral induced oxidative stress, mitochondria damage and toxicolog ical effects. Antiretroviral drugs are associated with toxicological effects which may involve redox imbalance, but more studies are required to correlate antiretroviral toxicities with oxidative stress.
{"title":"ANTIRETROVIRAL TOXICITY AND OXIDATIVE STRESS","authors":"A. Elias, B. Nelson, Deo Oputiri, Oru-Bo Precious Geoffrey","doi":"10.3844/AJPTSP.2013.187.196","DOIUrl":"https://doi.org/10.3844/AJPTSP.2013.187.196","url":null,"abstract":"Antiretroviral drugs are used for the treatment of human immunodeficiency virus, they are used as combination regimens to achieve the highest possibl e benefit, tolerability, compliance and to diminish the risk of resistance development. Reports from precli nical and clinical studies have linked antiretrovir als with some toxicological effects which could be associate d with redox imbalance (oxidative stress). This stimulated us to review relevant literature on the relationship between antiretroviral induced toxicol ogical effects and redox imbalance. Available literature o n antiretroviral associated toxicological effects a nd oxidative stress were comprehensively reviewed. Lit erature showed that antiretrovirals are associated with toxicological effects which includes hepatotox icity, cardiotoxicity, hematotoxicity and nephrotoxicity. Reports in animal studies also show ed that these toxicological effects could be associated with oxidative stress through the genera tion of oxidative radicals, depletion of antioxidan ts and antioxidant enzymes leading to mitochondria damage in the heart, kidney, liver brain and other organs. In humans, studies also showed that antiret rovirals are associated with lipid peroxidation, depletion of antoxidants and antioxidant enzymes wh ich are elements of oxidative stress. Furthermore it was observed that supplementations with some ant ioxidants mitigated antiretroviral induced oxidative stress, mitochondria damage and toxicolog ical effects. Antiretroviral drugs are associated with toxicological effects which may involve redox imbalance, but more studies are required to correlate antiretroviral toxicities with oxidative stress.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"10 1","pages":"187-196"},"PeriodicalIF":0.0,"publicationDate":"2013-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90521913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-11-13DOI: 10.3844/AJPTSP.2013.179.186
Kolawole O. Timothy, A. Adewumi, A. O. Emmanuel, Akiibinu M. Olayemi
Diabetes is one of the major health problems around the world and the incidence of this metabolic disorder is on the increase. Current therapeutic interventions have not done much in preventing complications of diabetes. Therefore this study investigated the effect of ethanolic extract of Newbouldia laevis leaves (NLet) on lipid peroxidation and glycosylation of hemoglobin, which are pathological indicators of diabetes mellitus. Diabetes was induced in Wistar rats by intravenous injection of streptozotocin (60 mg kg-1). Diabetic rats were then treated orally with NLet for 28 days. After the treatment, the concentration of Malondialdehyde (MDA) in the liver, kidney and pancreas of the rats was estimated. Fasting blood glucose was determined and oral glucose tolerance test was also carried out. Other groups of STZ-diabetic rats were treated for 8 weeks and percentage glycosylated hemoglobin (HbA1c) was measured. Fasting blood glucose of treated diabetic rats significantly (p
{"title":"Ethanolic Extract of Leaves of Newbouldia laevis Attenuates Glycosylation of Hemoglobin and Lipid Peroxidation in Diabetic Rats","authors":"Kolawole O. Timothy, A. Adewumi, A. O. Emmanuel, Akiibinu M. Olayemi","doi":"10.3844/AJPTSP.2013.179.186","DOIUrl":"https://doi.org/10.3844/AJPTSP.2013.179.186","url":null,"abstract":"Diabetes is one of the major health problems around the world and the incidence of this metabolic disorder is on the increase. Current therapeutic interventions have not done much in preventing complications of diabetes. Therefore this study investigated the effect of ethanolic extract of Newbouldia laevis leaves (NLet) on lipid peroxidation and glycosylation of hemoglobin, which are pathological indicators of diabetes mellitus. Diabetes was induced in Wistar rats by intravenous injection of streptozotocin (60 mg kg-1). Diabetic rats were then treated orally with NLet for 28 days. After the treatment, the concentration of Malondialdehyde (MDA) in the liver, kidney and pancreas of the rats was estimated. Fasting blood glucose was determined and oral glucose tolerance test was also carried out. Other groups of STZ-diabetic rats were treated for 8 weeks and percentage glycosylated hemoglobin (HbA1c) was measured. Fasting blood glucose of treated diabetic rats significantly (p","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"267 1","pages":"179-186"},"PeriodicalIF":0.0,"publicationDate":"2013-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77163201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-11-04DOI: 10.3844/AJPTSP.2013.170.178
C. M. Hossain, B. S. Satapathy, Laboni Mondal, Samrat Chakraborty, B. Mukherjee
Diabetes mellitus and hepatocellular carcinoma both have detrimental impact on health worldwide. Type II diabetes and liver cancer share many causative fact ors, but biological correlation between the two dis eases still remains elusive. The study was aimed to evalu ate the effect of induction of diabetes during the development of hepatocarcinogenesis in rats. Rats w ere divided into four groups namely, normal control , diabetic control, carcinogen control and carcinogen treated rats treated with streptozotocin (to make them diabetic). Hepatocarcinogenesis was initiated in ra ts by diethylnitrosamine (200 mg kg -1 body weight, single i.p. injection on day 0 only). Then 2-acetyl aminoflourene (0.5% w/w) was given daily in diet fo r 18 weeks to promote the carcinogenesis. On the 16th week, streptozotocin (65 mg kg -1 body weight, single i.p. injection) was administered to initiate diabetes in rats. On the 20th week, animals were sacrificed an d various biochemical changes and histopathological a lterations in liver were investigated. Carcinogen t reated rats made diabetic had significantly lower cytochro me P-450 content as compared to diabetic control ra ts and had slightly elevated cytochrome P-450 level as compared to that of carcinogen control rats. Marke d enhancements of UDP-glucuronosyl transferase, glutathione S-transferase activities and lipid peroxidat ion levels were observed in carcinogen treated rats mad e diabetic as compared to those activities and leve ls in diabetic control and carcinogen control rats. Histo pathological investigation of hepatic tissue has fa voured the rapid progress of development of hepatocellular carcinoma in carcinogen treated rats made diabetic . In conclusion, induction of diabetes during the develo pment of hepatocellular carcinogenesis inevitably promotes the progression of the later disease.
糖尿病和肝细胞癌都对人类健康造成危害。2型糖尿病和肝癌有许多共同的致病因素，但两种疾病之间的生物学相关性仍然难以捉摸。本研究旨在评价糖尿病在大鼠肝癌发生过程中的诱导作用。将大鼠分为四组，即正常对照组、糖尿病对照组、致癌物对照组和致癌物治疗组，给予链脲佐菌素(致糖尿病)治疗。小鼠经二乙基亚硝胺(200 mg kg -1体重，仅在第0天单口注射)引发肝癌发生。2-乙酰基氨基芴(0.5% w/w)连续18周促进癌变。第16周给予链脲佐菌素(65 mg kg -1体重，单次腹腔注射)引起大鼠糖尿病。第20周处死动物，观察肝脏的各种生化变化和组织病理学改变。致癌物处理的糖尿病大鼠细胞色素P-450含量明显低于糖尿病对照大鼠，细胞色素P-450含量略高于致癌物对照大鼠。与糖尿病对照组和致癌物对照组相比，致癌物处理的糖尿病大鼠的udp -葡萄糖醛基转移酶、谷胱甘肽s -转移酶活性和脂质过氧化水平明显增强。肝组织病理检查证实了致癌物治疗的糖尿病大鼠肝细胞癌的快速发展。总之，在肝细胞癌发展过程中诱导糖尿病不可避免地促进后期疾病的进展。
{"title":"EFFECT OF STREPTOZOTOCIN-INDUCED HYPERGLYCEMIA ON THE PROGRESSION OF HEPATOCARCINOGENESIS IN RATS","authors":"C. M. Hossain, B. S. Satapathy, Laboni Mondal, Samrat Chakraborty, B. Mukherjee","doi":"10.3844/AJPTSP.2013.170.178","DOIUrl":"https://doi.org/10.3844/AJPTSP.2013.170.178","url":null,"abstract":"Diabetes mellitus and hepatocellular carcinoma both have detrimental impact on health worldwide. Type II diabetes and liver cancer share many causative fact ors, but biological correlation between the two dis eases still remains elusive. The study was aimed to evalu ate the effect of induction of diabetes during the development of hepatocarcinogenesis in rats. Rats w ere divided into four groups namely, normal control , diabetic control, carcinogen control and carcinogen treated rats treated with streptozotocin (to make them diabetic). Hepatocarcinogenesis was initiated in ra ts by diethylnitrosamine (200 mg kg -1 body weight, single i.p. injection on day 0 only). Then 2-acetyl aminoflourene (0.5% w/w) was given daily in diet fo r 18 weeks to promote the carcinogenesis. On the 16th week, streptozotocin (65 mg kg -1 body weight, single i.p. injection) was administered to initiate diabetes in rats. On the 20th week, animals were sacrificed an d various biochemical changes and histopathological a lterations in liver were investigated. Carcinogen t reated rats made diabetic had significantly lower cytochro me P-450 content as compared to diabetic control ra ts and had slightly elevated cytochrome P-450 level as compared to that of carcinogen control rats. Marke d enhancements of UDP-glucuronosyl transferase, glutathione S-transferase activities and lipid peroxidat ion levels were observed in carcinogen treated rats mad e diabetic as compared to those activities and leve ls in diabetic control and carcinogen control rats. Histo pathological investigation of hepatic tissue has fa voured the rapid progress of development of hepatocellular carcinoma in carcinogen treated rats made diabetic . In conclusion, induction of diabetes during the develo pment of hepatocellular carcinogenesis inevitably promotes the progression of the later disease.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"34 1","pages":"170-178"},"PeriodicalIF":0.0,"publicationDate":"2013-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86948271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-10-30DOI: 10.3844/AJPTSP.2013.164.169
S. Fatemi, M. Iranmanesh, F. Balooch
The present research is aimed to characterize the potential efficiency of two chelators after chromium(VI) administration for 60 days following two doses of 15 and 30 mg kg-1 chromium(VI) per body weight daily to male rats. However, the hypothesis that the two chelators might be more efficient as combined therapy than as single therapy in removing chromium(VI) from bood serum was considered. In this way, two known chelators deferasirox and deferiprone were chosen and tested in the acute rat model. Two chelators were given orally as a single or combined therapy for a period of one week. Chromium(VI) and iron concentrations in blood were determined by flame atomic absorption spectroscopy method. Chromium is one of the most widely used industrial metals. Several million workers worldwide are estimated to be exposed to chromium compounds in an array of industries. Chromium(VI) is more readily absorbed by both inhalation and oral routes. Ingestion of large amounts of chromium(VI) can lead to severe respiratory, cardiovascular, gastrointestinal, hepatic and renal damage and potentially death. The combined chelation therapy results show that deferasirox and deferiprone are able to remove chromium(VI) ions from bood while iron concentration returned to the normal level and symptoms are also decreased.
{"title":"Effect of Chromium(VI) on Serum Iron and Removal of its Toxicity by Combining Deferasirox and Deferiprone Chelators in Rats","authors":"S. Fatemi, M. Iranmanesh, F. Balooch","doi":"10.3844/AJPTSP.2013.164.169","DOIUrl":"https://doi.org/10.3844/AJPTSP.2013.164.169","url":null,"abstract":"The present research is aimed to characterize the potential efficiency of two chelators after chromium(VI) administration for 60 days following two doses of 15 and 30 mg kg-1 chromium(VI) per body weight daily to male rats. However, the hypothesis that the two chelators might be more efficient as combined therapy than as single therapy in removing chromium(VI) from bood serum was considered. In this way, two known chelators deferasirox and deferiprone were chosen and tested in the acute rat model. Two chelators were given orally as a single or combined therapy for a period of one week. Chromium(VI) and iron concentrations in blood were determined by flame atomic absorption spectroscopy method. Chromium is one of the most widely used industrial metals. Several million workers worldwide are estimated to be exposed to chromium compounds in an array of industries. Chromium(VI) is more readily absorbed by both inhalation and oral routes. Ingestion of large amounts of chromium(VI) can lead to severe respiratory, cardiovascular, gastrointestinal, hepatic and renal damage and potentially death. The combined chelation therapy results show that deferasirox and deferiprone are able to remove chromium(VI) ions from bood while iron concentration returned to the normal level and symptoms are also decreased.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"72 1","pages":"164-169"},"PeriodicalIF":0.0,"publicationDate":"2013-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85960523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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