Pub Date : 2019-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029341
Miao Chen, V. P. Samuel, Yi Wu, Minyan Dang, Yukiat Lin, R. Sriramaneni, S. Sah, Gopala Krishna Chinnaboina, Guang-lin Zhang
The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.
{"title":"Nrf2/HO-1 Mediated Protective Activity of Genistein Against Doxorubicin-Induced Cardiac Toxicity.","authors":"Miao Chen, V. P. Samuel, Yi Wu, Minyan Dang, Yukiat Lin, R. Sriramaneni, S. Sah, Gopala Krishna Chinnaboina, Guang-lin Zhang","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029341","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029341","url":null,"abstract":"The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87206498","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 : 2019-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029196
Yanxia Ji, Zhenqiao Kang, Ning Kang, Yanzheng Zhao, Q. Guo, Yongge Chen
BACKGROUND Natural active components have been reported to serve as adjuvant medications in the clinical practice of cancer therapeutics. However, the antineoplastic roles of atractylenolide III (ATL) are rarely reported. In the present study, we assessed the functions of ATL combined with docetaxel in gastric cancer cells. METHODS Cell viability and cytotoxic activity were evaluated using CCK-8 and LDH-based cytotoxicity assays, respectively. Protein expression levels were measured by western blotting analysis. Annexin V-FITC/PI staining was used to evaluate cell apoptosis using flow cytometry. RESULTS AGS and SGC-7901 cell viability was significantly inhibited in ATL combined with docetaxel group compared with docetaxel treatment alone. The levels of LDH, apoptosis rate, and the ratio of BAX to Bcl-2 were significantly elevated in combination treatment group compared to docetaxel treatment alone. Intriguingly, docetaxel combined with ATL resulted in a significant decrease in FGFR1, FGFR2, and FGFR4 protein expression compared with docetaxel treatment alone. Knockout of FGFR1, -2, and -4 exhibited a similar role of medications to inhibit growth and induce apoptosis in AGS and SGC-7901 cells. CONCLUSIONS ATL and docetaxel treatment performed the synergistic effects on the inhibition of growth and induction of apoptosis in gastric cancer cells, and the underlying mechanism was mediated, at least partially, through the inhibition of FGFR1, -2, and -4.
{"title":"Atractylenolide III Enhances the Anti-Neoplastic Efficacy of Docetaxel in Gastric Cancer Cell by Inhibiting Fibroblast Growth Factor Receptors 1, -2, and -4 Expression.","authors":"Yanxia Ji, Zhenqiao Kang, Ning Kang, Yanzheng Zhao, Q. Guo, Yongge Chen","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029196","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029196","url":null,"abstract":"BACKGROUND Natural active components have been reported to serve as adjuvant medications in the clinical practice of cancer therapeutics. However, the antineoplastic roles of atractylenolide III (ATL) are rarely reported. In the present study, we assessed the functions of ATL combined with docetaxel in gastric cancer cells. METHODS Cell viability and cytotoxic activity were evaluated using CCK-8 and LDH-based cytotoxicity assays, respectively. Protein expression levels were measured by western blotting analysis. Annexin V-FITC/PI staining was used to evaluate cell apoptosis using flow cytometry. RESULTS AGS and SGC-7901 cell viability was significantly inhibited in ATL combined with docetaxel group compared with docetaxel treatment alone. The levels of LDH, apoptosis rate, and the ratio of BAX to Bcl-2 were significantly elevated in combination treatment group compared to docetaxel treatment alone. Intriguingly, docetaxel combined with ATL resulted in a significant decrease in FGFR1, FGFR2, and FGFR4 protein expression compared with docetaxel treatment alone. Knockout of FGFR1, -2, and -4 exhibited a similar role of medications to inhibit growth and induce apoptosis in AGS and SGC-7901 cells. CONCLUSIONS ATL and docetaxel treatment performed the synergistic effects on the inhibition of growth and induction of apoptosis in gastric cancer cells, and the underlying mechanism was mediated, at least partially, through the inhibition of FGFR1, -2, and -4.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88845971","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 : 2019-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2019030301
Weiwei Chen, Hongjing Zhang, Yue Liu
Fucoxanthin, a potent carotenoid present in various natural sources especially from seaweeds; it exhibits several biological effects like anti-neoplastic, anti-mutagenic, anti-diabetic, anti-obesity and anti-inflammatory actions. Fucoxanthin role in chemoprevention of lung cancer in mouse model induced using benzo(a)pyrene [B(a)P] has been presented here. Oral administration of fucoxanthin with and without B(a)P were studied, the results from our study shows that fucoxanthin significantly decreased tumor progression in mice exposed to B(a)P, the obtained data were correlated with increased antioxidant, apoptosis and decreased tumour marker and anti-apoptotic molecules. With respect to apoptosis, fucoxanthin treated animals shows increased apoptosis compared to tumor induced mice by increased expression of caspase 9 and 3 and decreased expression of anti-apoptotic Bcl2 protein. Finally, histopathological and immuno histochemical analysis also revealed that fucoxanthin shows potent anticancer agent by bringing back the damaged tissue treated with B(a)P and also decreases the expression of PCNA in cancer induced mice. The anticancer effect of fucoxanthin may be attributed by several independent mechanisms which play a important roles in the prevention of cancer development, there is also substantial evidences to show that fucoxanthin acts indirectly by increasing the antioxidant capacity of affected tissue and prepared to cope up with oxidative stress which is proved in our study. Thus from our study it is clearly established that fucoxanthin act as a persuasive anticancer drug against lung cancer.
{"title":"Anti-Inflammatory and Apoptotic Signaling Effect of Fucoxanthin on Benzo(A)Pyrene-Induced Lung Cancer in Mice.","authors":"Weiwei Chen, Hongjing Zhang, Yue Liu","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019030301","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019030301","url":null,"abstract":"Fucoxanthin, a potent carotenoid present in various natural sources especially from seaweeds; it exhibits several biological effects like anti-neoplastic, anti-mutagenic, anti-diabetic, anti-obesity and anti-inflammatory actions. Fucoxanthin role in chemoprevention of lung cancer in mouse model induced using benzo(a)pyrene [B(a)P] has been presented here. Oral administration of fucoxanthin with and without B(a)P were studied, the results from our study shows that fucoxanthin significantly decreased tumor progression in mice exposed to B(a)P, the obtained data were correlated with increased antioxidant, apoptosis and decreased tumour marker and anti-apoptotic molecules. With respect to apoptosis, fucoxanthin treated animals shows increased apoptosis compared to tumor induced mice by increased expression of caspase 9 and 3 and decreased expression of anti-apoptotic Bcl2 protein. Finally, histopathological and immuno histochemical analysis also revealed that fucoxanthin shows potent anticancer agent by bringing back the damaged tissue treated with B(a)P and also decreases the expression of PCNA in cancer induced mice. The anticancer effect of fucoxanthin may be attributed by several independent mechanisms which play a important roles in the prevention of cancer development, there is also substantial evidences to show that fucoxanthin acts indirectly by increasing the antioxidant capacity of affected tissue and prepared to cope up with oxidative stress which is proved in our study. Thus from our study it is clearly established that fucoxanthin act as a persuasive anticancer drug against lung cancer.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89565913","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 : 2019-01-01DOI: 10.1615/jenvironpatholtoxicoloncol.2019030625
Wei Zhao, Yi Tang, Yang Yang, Min Wang, Haiyang Yu
Certain mechanical stimuli-particularly low-magnitude, high-frequency vibration-could induce bone marrow stem cell osteogenic differentiation and promote bone formation via Wnt signaling pathway, although the molecular mechanism is still unclear. In this study, we found that miR-335-5p is significantly upregulated after low-magnitude, high-frequency vibration, which suppresses the expression of the Wnt signaling inhibitor Dickkopf-related protein 1. Inhibition of miR-335-5p greatly reduced the osteogenic differentiation. Furthermore, the increase of miR-335-5p level was also confirmed in vivo after LMHF vibration in rabbit. Our study elucidates the prominent role of miRNAs that links the LMHF vibration and osteogenic differentiation.
{"title":"Low-Magnitude, High-Frequency Vibration Promotes Osteogenic Differentiation via Intensifying miRNA-335-5p Expression.","authors":"Wei Zhao, Yi Tang, Yang Yang, Min Wang, Haiyang Yu","doi":"10.1615/jenvironpatholtoxicoloncol.2019030625","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2019030625","url":null,"abstract":"Certain mechanical stimuli-particularly low-magnitude, high-frequency vibration-could induce bone marrow stem cell osteogenic differentiation and promote bone formation via Wnt signaling pathway, although the molecular mechanism is still unclear. In this study, we found that miR-335-5p is significantly upregulated after low-magnitude, high-frequency vibration, which suppresses the expression of the Wnt signaling inhibitor Dickkopf-related protein 1. Inhibition of miR-335-5p greatly reduced the osteogenic differentiation. Furthermore, the increase of miR-335-5p level was also confirmed in vivo after LMHF vibration in rabbit. Our study elucidates the prominent role of miRNAs that links the LMHF vibration and osteogenic differentiation.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90242875","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 : 2019-01-01DOI: 10.1615/jenvironpatholtoxicoloncol.2019029075
Ajay Patle, K. Hatware, K. Patil, Sanjay Sharma, G. Gupta
BACKGROUND Urolithiasis is the most common renal system pathology; it affects the health of a many people. Because urolithiasis leads to severe pain, it influences the patient in many aspects. The management of urolithiasis is essential. Herein, we discuss the limitations of the management of urolithiasis with conventional drugs and the possibilities of using natural or herbal pharmacologically active agents beyond conventional drugs. PURPOSE The drugs presently used for the treatment of urolithiasis have many adverse side effects; therefore, alternatives are needed. Traditional literature suggests that many herbal or natural medicines can be easily made available for the management of urolithiasis and its consequences. METHOD The data used for this study were collected from various research /review articles, Internet sources, and text books. Literature regarding epidemiology and pharmacological studies performed by various researchers were taken into consideration in this review. The data from the last few decades, reported in different formats, were analyzed. CONCLUSION The present review reveals the severity of the progression of the occurrence of urolithiasis worldwide. The epidemiology gave in this review clearly indicates that stress-related factors and dietary complications, the key factors in the development of urolithiasis. are increasing. In this review, we acknowledge the limitations of conventional therapy. Many natural drug options are abundantly available throughout the world and can be useful for the management of urolithiasis. Future Perspectives: The development of a suitable formulation of bioactive components obtained from natural sources is being widely researched. However, traditional remedies that are very helpful in the management of urolithiasis and its related complications require scientific support and appropriate standardization for the assessment of their quality and dosage.
{"title":"Role of Herbal Medicine in the Management of Urolithiasis- A Review for Future Perspectives.","authors":"Ajay Patle, K. Hatware, K. Patil, Sanjay Sharma, G. Gupta","doi":"10.1615/jenvironpatholtoxicoloncol.2019029075","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2019029075","url":null,"abstract":"BACKGROUND Urolithiasis is the most common renal system pathology; it affects the health of a many people. Because urolithiasis leads to severe pain, it influences the patient in many aspects. The management of urolithiasis is essential. Herein, we discuss the limitations of the management of urolithiasis with conventional drugs and the possibilities of using natural or herbal pharmacologically active agents beyond conventional drugs. PURPOSE The drugs presently used for the treatment of urolithiasis have many adverse side effects; therefore, alternatives are needed. Traditional literature suggests that many herbal or natural medicines can be easily made available for the management of urolithiasis and its consequences. METHOD The data used for this study were collected from various research /review articles, Internet sources, and text books. Literature regarding epidemiology and pharmacological studies performed by various researchers were taken into consideration in this review. The data from the last few decades, reported in different formats, were analyzed. CONCLUSION The present review reveals the severity of the progression of the occurrence of urolithiasis worldwide. The epidemiology gave in this review clearly indicates that stress-related factors and dietary complications, the key factors in the development of urolithiasis. are increasing. In this review, we acknowledge the limitations of conventional therapy. Many natural drug options are abundantly available throughout the world and can be useful for the management of urolithiasis. Future Perspectives: The development of a suitable formulation of bioactive components obtained from natural sources is being widely researched. However, traditional remedies that are very helpful in the management of urolithiasis and its related complications require scientific support and appropriate standardization for the assessment of their quality and dosage.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75578244","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 : 2019-01-01DOI: 10.1615/jenvironpatholtoxicoloncol.2019026470
Gulru Gurdemir, P. Erkekoğlu, Aylin Balcı, Unzile Sur, Gizem Ozkemahli, E. Tutkun, H. Yılmaz, A. Asci, B. Kocer-Gumusel
Di(2-ethylhexyl)phthalate (DEHP) is the most widely used phthalate. DEHP is highly used in PVC floorings and PVC windows and carpeting. The objective of this study was to determine sex hormone levels, oxidative stress parameters, selenium levels, DNA damage, and phthalate levels in plastics workers (n = 24, age = 20-58 years) working in the production of rubber mechanical goods and exposed to DEHP in workplace. The control group (n = 29, age = 25-54, all male) was selected from age-matched healthy adults. Antioxidant parameters and DNA damage were determined by spectrophotometry. Selenium levels were determined by atomic absorption spectroscopy. Plasma hormone levels were measured by chemiluminescence microparticle immunoassay. Plasma phthalate levels were determined by high-pressure liquid chromatography. Plastic workers had lower serum testosterone and free T4 levels and higher follicle-stimulating hormone levels vs. controls. Liver enzyme activities were markedly higher in workers vs. controls. There were also increases in plasma glutathione peroxidase levels and marked decreases in plasma selenium and erythrocyte total glutathione levels in plastics workers (P < 0.05 vs. control). Plasma 8-hydroxy-2'-deoxyguanosine levels were 14-fold higher in plastics workers than in controls. Plasma DEHP and mono(2-ethylhexyl)phthalate were also markedly higher in workers vs. controls. The results of this study show that occupational exposure to DEHP may lead to disturbances in sex hormones, increased liver problems, higher oxidative stress and DNA damage levels, and lower trace element concentrations in workers. More comprehensive and mechanistic studies with higher numbers of subjects are needed to show the unwanted effects of occupational exposure to DEHP.
{"title":"Oxidative Stress Parameters, Selenium Levels, DNA Damage, and Phthalate Levels in Plastic Workers.","authors":"Gulru Gurdemir, P. Erkekoğlu, Aylin Balcı, Unzile Sur, Gizem Ozkemahli, E. Tutkun, H. Yılmaz, A. Asci, B. Kocer-Gumusel","doi":"10.1615/jenvironpatholtoxicoloncol.2019026470","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2019026470","url":null,"abstract":"Di(2-ethylhexyl)phthalate (DEHP) is the most widely used phthalate. DEHP is highly used in PVC floorings and PVC windows and carpeting. The objective of this study was to determine sex hormone levels, oxidative stress parameters, selenium levels, DNA damage, and phthalate levels in plastics workers (n = 24, age = 20-58 years) working in the production of rubber mechanical goods and exposed to DEHP in workplace. The control group (n = 29, age = 25-54, all male) was selected from age-matched healthy adults. Antioxidant parameters and DNA damage were determined by spectrophotometry. Selenium levels were determined by atomic absorption spectroscopy. Plasma hormone levels were measured by chemiluminescence microparticle immunoassay. Plasma phthalate levels were determined by high-pressure liquid chromatography. Plastic workers had lower serum testosterone and free T4 levels and higher follicle-stimulating hormone levels vs. controls. Liver enzyme activities were markedly higher in workers vs. controls. There were also increases in plasma glutathione peroxidase levels and marked decreases in plasma selenium and erythrocyte total glutathione levels in plastics workers (P < 0.05 vs. control). Plasma 8-hydroxy-2'-deoxyguanosine levels were 14-fold higher in plastics workers than in controls. Plasma DEHP and mono(2-ethylhexyl)phthalate were also markedly higher in workers vs. controls. The results of this study show that occupational exposure to DEHP may lead to disturbances in sex hormones, increased liver problems, higher oxidative stress and DNA damage levels, and lower trace element concentrations in workers. More comprehensive and mechanistic studies with higher numbers of subjects are needed to show the unwanted effects of occupational exposure to DEHP.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81912592","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 : 2019-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2019028294
G. Ramalingayya, K. Gourishetti, P. Nayak, C. Rao, A. Kishore, S. Alnaseer, S. Hussain, K. Nandakumar
Chemobrain is a significant post-chemotherapy complication for which no approved treatments are available. We had previously identified that rutin inhibits doxorubicin (Dox-) -induced cognitive decline in healthy rats. However, it was important to also establish that it does so in rats with mammary carcinoma without compromising Dox's antitumor potential. Mammary carcinoma was induced in female rats by intraperitonial administration of N-methyl-N-nitrosourea (i.p.). Rats that developed mammary carcinoma were treated with Dox after pretreatment with vehicle or rutin. After Dox exposure (50 days), episodic and spatial memory was assessed using the novel object recognition task and the Morris water maze, respectively. Tumor progression was evaluated by measurement of tumor weight and volume and histological analysis. Blood samples were collected to estimate hematological parameters. Oxidative status and TNF-α levels were estimated in brain homogenates. Dox treatment significantly reduced tumor size and volume. Pretreatment with rutin did not significantly alter Dox's tumor suppression potential, suggesting that it does not influence Dox's anticancer activity. In addition, rutin ameliorated Dox-induced cognitive decline, myelosuppression, and brain oxidative stress. The present study indicates that rutin protects against Dox-induced cognitive decline and myelosuppression without affecting its antitumor potential.
{"title":"Rutin Protects against Doxorubicin-Induced Cognitive Dysfunction While Retaining the Anticancer Potential of Dox in a Murine Model of N-Methyl-N-Nitrosourea - Induced Mammary Carcinoma.","authors":"G. Ramalingayya, K. Gourishetti, P. Nayak, C. Rao, A. Kishore, S. Alnaseer, S. Hussain, K. Nandakumar","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019028294","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019028294","url":null,"abstract":"Chemobrain is a significant post-chemotherapy complication for which no approved treatments are available. We had previously identified that rutin inhibits doxorubicin (Dox-) -induced cognitive decline in healthy rats. However, it was important to also establish that it does so in rats with mammary carcinoma without compromising Dox's antitumor potential. Mammary carcinoma was induced in female rats by intraperitonial administration of N-methyl-N-nitrosourea (i.p.). Rats that developed mammary carcinoma were treated with Dox after pretreatment with vehicle or rutin. After Dox exposure (50 days), episodic and spatial memory was assessed using the novel object recognition task and the Morris water maze, respectively. Tumor progression was evaluated by measurement of tumor weight and volume and histological analysis. Blood samples were collected to estimate hematological parameters. Oxidative status and TNF-α levels were estimated in brain homogenates. Dox treatment significantly reduced tumor size and volume. Pretreatment with rutin did not significantly alter Dox's tumor suppression potential, suggesting that it does not influence Dox's anticancer activity. In addition, rutin ameliorated Dox-induced cognitive decline, myelosuppression, and brain oxidative stress. The present study indicates that rutin protects against Dox-induced cognitive decline and myelosuppression without affecting its antitumor potential.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83143909","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 : 2019-01-01DOI: 10.1615/JEnvironPatholToxicolOncol.2019028792
Achummantakath Hashim, Haneena Fathima, R. Muhammed, D. R. D. Neevan
Donor blood is usually screened for some risk factors, such as hepatitis, HIV, and malarial parasites, but it is not routinely screened for heavy metals although their adverse effects on the human body have been proved by a number of studies. In this study, an attempt was made to determine the effect of smoking on concentration of cadmium, nickel, and lead in donor blood. A semistructured questionnaire was prepared and given to participants. It showed that 79% (two groups: 65 smokers and 65 nonsmokers) smoked at least one cigarette per day. Collected blood samples were then subjected to atomic absorption spectrometry (AAS). In comparing blood levels between smoking and nonsmoking participants, we noted a high positive correlation between lead and nickel concentrations. There were statistically significant correlations between cadmium, lead, and nickel concentrations in the blood of smokers and nonsmokers. Moreover, because a substantial percentage of blood donors may be smokers and blood donation does not always meet demand, it would be difficult to completely exclude smokers from donating blood. Our findings indicate the need to screen for heavy metals when transfusing blood to the elderly, neonates, and infants, and to avoid transfusion of blood and blood products if levels are in the toxic range.
{"title":"Analysis of Lead, Cadmium, and Nickel in Blood Donors in Relation to Smoking-A Comparative Study.","authors":"Achummantakath Hashim, Haneena Fathima, R. Muhammed, D. R. D. Neevan","doi":"10.1615/JEnvironPatholToxicolOncol.2019028792","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2019028792","url":null,"abstract":"Donor blood is usually screened for some risk factors, such as hepatitis, HIV, and malarial parasites, but it is not routinely screened for heavy metals although their adverse effects on the human body have been proved by a number of studies. In this study, an attempt was made to determine the effect of smoking on concentration of cadmium, nickel, and lead in donor blood. A semistructured questionnaire was prepared and given to participants. It showed that 79% (two groups: 65 smokers and 65 nonsmokers) smoked at least one cigarette per day. Collected blood samples were then subjected to atomic absorption spectrometry (AAS). In comparing blood levels between smoking and nonsmoking participants, we noted a high positive correlation between lead and nickel concentrations. There were statistically significant correlations between cadmium, lead, and nickel concentrations in the blood of smokers and nonsmokers. Moreover, because a substantial percentage of blood donors may be smokers and blood donation does not always meet demand, it would be difficult to completely exclude smokers from donating blood. Our findings indicate the need to screen for heavy metals when transfusing blood to the elderly, neonates, and infants, and to avoid transfusion of blood and blood products if levels are in the toxic range.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84084292","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 : 2019-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2019027318
B. Rohini, T. Akther, M. Waseem, Jasim Khan, M. Kashif, S. Hemalatha
In our current study, we synthesized silver nanoparticles (AgNPs) from an aqueous seed extract of Nigella sativa. The seed extract contains phytochemical compounds including phenols, terpenoids, and flavonoids that may act as reducing agents and are able to convert metal ions to metal nanoparticles. The formation of synthesized AgNPs was characterized using UV-visible spectroscopy, Fourier transform infra-red spectroscopy (FT-IR), scanning electron microscopy (SEM) and energy dispersive analysis of X-rays (EDX). The efficacy of N-AgNPs against human breast cancer (MCF-7) cells was tested. The synthesized AgNPs displayed dose-dependent cytotoxicity (1-200 µg/mL) against MCF-7 cells. Morphological alterations of the cells also appeared as bright field images. Treatment of synthesized AgNPs altered the expression of Bax and Bcl-2 (apoptotic proteins) and COX-2 (inflammatory marker) in MCF-7 cells. To our knowledge, this is the first report demonstrating that N-AgNPs from Nigella sativa can induce apoptosis in MCF-7 cells.
{"title":"AgNPs from Nigella sativa Control Breast Cancer: An In Vitro Study.","authors":"B. Rohini, T. Akther, M. Waseem, Jasim Khan, M. Kashif, S. Hemalatha","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019027318","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019027318","url":null,"abstract":"In our current study, we synthesized silver nanoparticles (AgNPs) from an aqueous seed extract of Nigella sativa. The seed extract contains phytochemical compounds including phenols, terpenoids, and flavonoids that may act as reducing agents and are able to convert metal ions to metal nanoparticles. The formation of synthesized AgNPs was characterized using UV-visible spectroscopy, Fourier transform infra-red spectroscopy (FT-IR), scanning electron microscopy (SEM) and energy dispersive analysis of X-rays (EDX). The efficacy of N-AgNPs against human breast cancer (MCF-7) cells was tested. The synthesized AgNPs displayed dose-dependent cytotoxicity (1-200 µg/mL) against MCF-7 cells. Morphological alterations of the cells also appeared as bright field images. Treatment of synthesized AgNPs altered the expression of Bax and Bcl-2 (apoptotic proteins) and COX-2 (inflammatory marker) in MCF-7 cells. To our knowledge, this is the first report demonstrating that N-AgNPs from Nigella sativa can induce apoptosis in MCF-7 cells.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86548679","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 : 2019-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029460
A. A. Mohamed Adil, Lavanya Vallinayagam, K. Chitra, Shazia Jamal, A. Pandurangan, Neesar Ahmed
In the present study, we investigated the effects of conditioned media (CM) collected from the cancer cell lines (K562, MCF-7, and HeLa) on peripheral blood mononuclear cells (PBMCs) isolated from the healthy human blood. The soluble factors in the CM are probably responsible for the differential mRNA expressions of Foxp3, Helios, Neuropilin- 1 (NRP-1), and glycoprotein A repetitions predominant (GARP), along with IFN-γ and TGF-β in PBMCs cultured with cancer cells CM. The PBMCs cultured with CM of K562 showed increased expression of Foxp3, Helios, NRP-1, GARP, IFN-γ, and TGF-β compared to PBMCs cultured with CM of MCF-7 and HeLa cells. In addition, the intracellular staining on PBMCs cultured with CM from cell lines were also evaluated for CD4, CD25, Foxp3, Helios, and NRP-1 by multicolor flow cytometry. The expression of CD4+CD25+Foxp3+, CD4+Helios+Foxp3+ and CD+NRP-1+Foxp3+ showed retarded cell population compared to control PBMCs. Our data suggest that soluble factors in CM of cancer cells may trigger the immune response in PBMCs resulting in a systematic response. Further research could lead to the identification of specific soluble factors that are involved in trafficking of cells into the immune cascades, which could be a safe and promising strategy for targeting human cancers.
{"title":"Increased Expression of TGF-β and IFN-γ in Peripheral Blood Mononuclear Cells (PBMCs) Cultured in Conditioned Medium (CM) of K562 Cell Culture.","authors":"A. A. Mohamed Adil, Lavanya Vallinayagam, K. Chitra, Shazia Jamal, A. Pandurangan, Neesar Ahmed","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029460","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029460","url":null,"abstract":"In the present study, we investigated the effects of conditioned media (CM) collected from the cancer cell lines (K562, MCF-7, and HeLa) on peripheral blood mononuclear cells (PBMCs) isolated from the healthy human blood. The soluble factors in the CM are probably responsible for the differential mRNA expressions of Foxp3, Helios, Neuropilin- 1 (NRP-1), and glycoprotein A repetitions predominant (GARP), along with IFN-γ and TGF-β in PBMCs cultured with cancer cells CM. The PBMCs cultured with CM of K562 showed increased expression of Foxp3, Helios, NRP-1, GARP, IFN-γ, and TGF-β compared to PBMCs cultured with CM of MCF-7 and HeLa cells. In addition, the intracellular staining on PBMCs cultured with CM from cell lines were also evaluated for CD4, CD25, Foxp3, Helios, and NRP-1 by multicolor flow cytometry. The expression of CD4+CD25+Foxp3+, CD4+Helios+Foxp3+ and CD+NRP-1+Foxp3+ showed retarded cell population compared to control PBMCs. Our data suggest that soluble factors in CM of cancer cells may trigger the immune response in PBMCs resulting in a systematic response. Further research could lead to the identification of specific soluble factors that are involved in trafficking of cells into the immune cascades, which could be a safe and promising strategy for targeting human cancers.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84128326","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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