Pub Date : 2022-04-01DOI: 10.1177/15593258221095327
Asma Naeem, A. Qureshi, Shafia Arshad, Anila Shehzadi, Asim Kamran, S. Noreen
The primary purpose of the current study was to study the possible pernicious effects of phosphine gas on enzyme activity alterations in Trogoderma granarium to determine its harmfulness to human beings after its prolonged exposure and intake. The saline extract of the adult Khapra beetle was biochemically analyzed at different doses, that is, from 10ppm to 30ppm, to accurately evaluate the effects of various phosphine concentrations (LC30 and LC50) on 2 distinct strains of this insect pest gathered from different godowns of Pakistan as resistant (Chitral [Chi], Haroon Abad [Hbd], and Lahore [Lhr]) and susceptible (Faqeer wali [Fqw], Khanewal [Khw], and Rawalpindi [Rwp]) populations. Our experimental results suggest that the enzyme levels (AcP, AkP, ALAT, ASAT, LDH, and ICDH) seemed to be elevated with increasing dosage of phosphine from 10ppm to 30ppm in the resistant populace of the susceptible ones. It also illustrates that phosphine and its residues can inhibit the workability of certain enzymes that are vital for respiration and neuro reactions in hexapods and mammals. It has detrimental effects of phosphine on human health profile to consume stored food products containing such tenacious enemies.
{"title":"Biochemical Toxic Response of Phosphine on Human Health Estimated From Enzymatic Variance in Trogoderma granarium","authors":"Asma Naeem, A. Qureshi, Shafia Arshad, Anila Shehzadi, Asim Kamran, S. Noreen","doi":"10.1177/15593258221095327","DOIUrl":"https://doi.org/10.1177/15593258221095327","url":null,"abstract":"The primary purpose of the current study was to study the possible pernicious effects of phosphine gas on enzyme activity alterations in Trogoderma granarium to determine its harmfulness to human beings after its prolonged exposure and intake. The saline extract of the adult Khapra beetle was biochemically analyzed at different doses, that is, from 10ppm to 30ppm, to accurately evaluate the effects of various phosphine concentrations (LC30 and LC50) on 2 distinct strains of this insect pest gathered from different godowns of Pakistan as resistant (Chitral [Chi], Haroon Abad [Hbd], and Lahore [Lhr]) and susceptible (Faqeer wali [Fqw], Khanewal [Khw], and Rawalpindi [Rwp]) populations. Our experimental results suggest that the enzyme levels (AcP, AkP, ALAT, ASAT, LDH, and ICDH) seemed to be elevated with increasing dosage of phosphine from 10ppm to 30ppm in the resistant populace of the susceptible ones. It also illustrates that phosphine and its residues can inhibit the workability of certain enzymes that are vital for respiration and neuro reactions in hexapods and mammals. It has detrimental effects of phosphine on human health profile to consume stored food products containing such tenacious enemies.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43107307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221092365
N. Abdel-Aziz, R. Haroun, Hebatallah E. Mohamed
Aim This work aims to investigate whether the pre-exposure to low dose/low dose rate (40 mGy, 2.2 mGy/hour) γ-radiation as a priming dose can produce a protective effect against the subsequent high one (4 Gy, .425 Gy/minute). Methods Rats were divided into Group I (control), Group II (L); exposed to 40 mGy, Group III (H); exposed to 4 Gy, and Group IV (L+H); exposed to 40 mGy 24 hours before the exposure to 4Gy. The molecular and biochemical changes related to oxidative stress, DNA damage, apoptosis, and mitochondrial activity in the liver and testis were studied 4 hours after irradiation. Results Exposure to 40 mGy before 4 Gy induced a significant increase in the levels of Nrf2, Nrf2 mRNA, TAC, and mitochondrial complexes I & II accompanied by a significant decrease in the levels of LPO, 8-OHdG, DNA fragmentation, TNF-α, caspase-3, and caspase-3 mRNA compared with H group. Conclusion Exposure to low-dose γ-radiation before a high dose provides protective mechanisms that allow the body to survive better after exposure to a subsequent high one via reducing the oxidative stress, DNA damage, and apoptosis-induced early after irradiation. However, further studies are required to identify the long-term effects of this low dose.
{"title":"Low-Dose Gamma Radiation Modulates Liver and Testis Tissues Response to Acute Whole Body Irradiation","authors":"N. Abdel-Aziz, R. Haroun, Hebatallah E. Mohamed","doi":"10.1177/15593258221092365","DOIUrl":"https://doi.org/10.1177/15593258221092365","url":null,"abstract":"Aim This work aims to investigate whether the pre-exposure to low dose/low dose rate (40 mGy, 2.2 mGy/hour) γ-radiation as a priming dose can produce a protective effect against the subsequent high one (4 Gy, .425 Gy/minute). Methods Rats were divided into Group I (control), Group II (L); exposed to 40 mGy, Group III (H); exposed to 4 Gy, and Group IV (L+H); exposed to 40 mGy 24 hours before the exposure to 4Gy. The molecular and biochemical changes related to oxidative stress, DNA damage, apoptosis, and mitochondrial activity in the liver and testis were studied 4 hours after irradiation. Results Exposure to 40 mGy before 4 Gy induced a significant increase in the levels of Nrf2, Nrf2 mRNA, TAC, and mitochondrial complexes I & II accompanied by a significant decrease in the levels of LPO, 8-OHdG, DNA fragmentation, TNF-α, caspase-3, and caspase-3 mRNA compared with H group. Conclusion Exposure to low-dose γ-radiation before a high dose provides protective mechanisms that allow the body to survive better after exposure to a subsequent high one via reducing the oxidative stress, DNA damage, and apoptosis-induced early after irradiation. However, further studies are required to identify the long-term effects of this low dose.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"20 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65580558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221097665
Fatima Shahbaz, N. Akhter, M. Shahid, M. Riaz, F. Anjum, F. Hussain
Worldwide, Verbascum thapsus is used for the treatment of various ailments owing to the presence of bioactives of therapeutic potential. Current study was planned to extract bioactives from V thapsus roots using methanol and water as solvents under stimulated effect of ultrasonic waves and characterize them to evaluate their potential benefits. Proximate analysis explored the presence of significant contents of protein, fats, fiber, organic and inorganic minerals. Fourier transform infrared spectra and high-performance liquid chromatography chromatogram indicated the presence of different phytochemicals having antioxidant potential as evidenced by total phenolic contents, total flavonoids content and 2,2-diphenyl-1-picrylhydrazyl activity of both extracts. Both extracts displayed excellent antimicrobial potential against Staphylococcus aureus (S aureus) and Fusarium Solani (F solani). Aqueous and methanolic extracts exhibited higher inhibition of biofilm made by Bacillus subtilis (B subtilis) as 55.09 and 61.58%, respectively in comparison to biofilm of Escherichia coli (E coli) as 48.11 and 36.51%, respectively. Methanol extract exhibited anti-amylase activity (IC50 5.26 ± .31 μg/mL) with an inhibition rate of 68.11% whereas IC50 of aqueous extract was 6.59 ± .53 μg/mL with an inhibition rate of 63.53%. Inhibitory potential against α-glucosidase (IC50 3.70 ± .94 ppm) was demonstrated by methanol extract in comparison to aqueous extract (IC50 7.58 ± .15). The study concluded that V thapsus roots have significant medicinal potential due to the presence of variety of bioactive molecules and can be used in pharmaceutical preparations.
{"title":"Ultrasound Assisted Extraction and Characterization of Bioactives From Verbascum thapsus Roots to Evaluate Their Antioxidant and Medicinal Potential","authors":"Fatima Shahbaz, N. Akhter, M. Shahid, M. Riaz, F. Anjum, F. Hussain","doi":"10.1177/15593258221097665","DOIUrl":"https://doi.org/10.1177/15593258221097665","url":null,"abstract":"Worldwide, Verbascum thapsus is used for the treatment of various ailments owing to the presence of bioactives of therapeutic potential. Current study was planned to extract bioactives from V thapsus roots using methanol and water as solvents under stimulated effect of ultrasonic waves and characterize them to evaluate their potential benefits. Proximate analysis explored the presence of significant contents of protein, fats, fiber, organic and inorganic minerals. Fourier transform infrared spectra and high-performance liquid chromatography chromatogram indicated the presence of different phytochemicals having antioxidant potential as evidenced by total phenolic contents, total flavonoids content and 2,2-diphenyl-1-picrylhydrazyl activity of both extracts. Both extracts displayed excellent antimicrobial potential against Staphylococcus aureus (S aureus) and Fusarium Solani (F solani). Aqueous and methanolic extracts exhibited higher inhibition of biofilm made by Bacillus subtilis (B subtilis) as 55.09 and 61.58%, respectively in comparison to biofilm of Escherichia coli (E coli) as 48.11 and 36.51%, respectively. Methanol extract exhibited anti-amylase activity (IC50 5.26 ± .31 μg/mL) with an inhibition rate of 68.11% whereas IC50 of aqueous extract was 6.59 ± .53 μg/mL with an inhibition rate of 63.53%. Inhibitory potential against α-glucosidase (IC50 3.70 ± .94 ppm) was demonstrated by methanol extract in comparison to aqueous extract (IC50 7.58 ± .15). The study concluded that V thapsus roots have significant medicinal potential due to the presence of variety of bioactive molecules and can be used in pharmaceutical preparations.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46008513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221095960
Jaweria Nisar, S. M. A. Shah, Muhammad Akram, S. Ayaz, A. Rashid
Picrorhiza kurroa (P.K) usually familiar as kutki is a well-known plant in the Ayurvedic system of medicine due to its reported activities including antidiabetic, antibacterial, antioxidant, antitumor, anti-inflammatory, and hepatoprotective. The current research was intended to evaluate the antioxidant, inhibition activity of the ethanolic, methanolic, and aqueous extracts of P.K roots against α-amylase and α-glucosidase in vitro, after the phytochemical analysis. For this purpose, P.K roots were extracted with ethanol (EthPk), methanol (MthPk), and distilled water (AqPk) and phytochemical study of the extracts were performed to recognize the total phenolic content (TPC) and total flavonoids content (TFC). Antioxidant capability of the extracts was assessed by FRAP, ABTS, and DPPH assay. α-amylase inhibitory and α-glucosidase inhibitory activities were also determined. Software SPSS-23 was used to statistically analyze with One Way ANOVA and results were stated as mean standard deviation. Result of the study showed that MthPk contained the maximum concentration of TPC and TFC than EthPk and AqEh. Antioxidants in terms of DPPH (lowest IC50 = .894 ± .57), FRAP (612.54 ± 11.73) and ABTS (406.42 ± 4.02) assay was also maximum in MthPk. MthPk was also showed maximum inhibition activity against α-amylase and α-glucosidase with lowest IC50 (.39 ± .41; .61 ± .24), respectively. The extracts α-amylase and α-glucosidase inhibitory activities order was as MthPk > EthPk> AqPk. Results clearly specified that the methanolic extract of Picrorhiza kurroa have the maximum antioxidant, α-amylase, and α-glucosidase inhibitory activities. A positive correlation of TPC, TFC with antioxidant, and α-amylase and α-glucosidase inhibition activities of the P.K roots were also shown. The plant has capability to diminish the oxidative stress and can be used to treat diabetes by inhibiting α-amylase and α-glucosidase actions.
{"title":"Phytochemical Screening, Antioxidant, and Inhibition Activity of Picrorhiza kurroa Against α-Amylase and α-Glucosidase","authors":"Jaweria Nisar, S. M. A. Shah, Muhammad Akram, S. Ayaz, A. Rashid","doi":"10.1177/15593258221095960","DOIUrl":"https://doi.org/10.1177/15593258221095960","url":null,"abstract":"Picrorhiza kurroa (P.K) usually familiar as kutki is a well-known plant in the Ayurvedic system of medicine due to its reported activities including antidiabetic, antibacterial, antioxidant, antitumor, anti-inflammatory, and hepatoprotective. The current research was intended to evaluate the antioxidant, inhibition activity of the ethanolic, methanolic, and aqueous extracts of P.K roots against α-amylase and α-glucosidase in vitro, after the phytochemical analysis. For this purpose, P.K roots were extracted with ethanol (EthPk), methanol (MthPk), and distilled water (AqPk) and phytochemical study of the extracts were performed to recognize the total phenolic content (TPC) and total flavonoids content (TFC). Antioxidant capability of the extracts was assessed by FRAP, ABTS, and DPPH assay. α-amylase inhibitory and α-glucosidase inhibitory activities were also determined. Software SPSS-23 was used to statistically analyze with One Way ANOVA and results were stated as mean standard deviation. Result of the study showed that MthPk contained the maximum concentration of TPC and TFC than EthPk and AqEh. Antioxidants in terms of DPPH (lowest IC50 = .894 ± .57), FRAP (612.54 ± 11.73) and ABTS (406.42 ± 4.02) assay was also maximum in MthPk. MthPk was also showed maximum inhibition activity against α-amylase and α-glucosidase with lowest IC50 (.39 ± .41; .61 ± .24), respectively. The extracts α-amylase and α-glucosidase inhibitory activities order was as MthPk > EthPk> AqPk. Results clearly specified that the methanolic extract of Picrorhiza kurroa have the maximum antioxidant, α-amylase, and α-glucosidase inhibitory activities. A positive correlation of TPC, TFC with antioxidant, and α-amylase and α-glucosidase inhibition activities of the P.K roots were also shown. The plant has capability to diminish the oxidative stress and can be used to treat diabetes by inhibiting α-amylase and α-glucosidase actions.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44762385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221093853
Tayyba Sattar, K. Jilani, Khalida Parveen, Zahid Mushataq, H. Nawaz, Maham Abdul Bari Khan
Methotrexate (MTX) is a common chemotherapeutical agent and folate antagonist with reported apoptotic activity in nucleated cells. The presented research work was planned to investigate the eryptotic effects of methotrexate after the exposure of erythrocytes to therapeutical doses (10–15 μM) of methotrexate. Eryptosis and the role of calcium in the stimulation of membrane blebbing were evaluated through the determination of mean cell volume. Oxidative stress induced by methotrexate (10–15 μM) was determined by antioxidative enzyme activities. Cytotoxic activity against human erythrocytes was examined through hemolysis assay. Exposure of erythrocytes to methotrexate results in significant reduction of superoxide dismutase, catalase, and superoxide dismutase activities at 10 and 15 μM in comparison to the untreated cells. Erythrocytes mean cell volume (MCV) was increased after 48 hours exposure of erythrocytes to methotrexate (10 μM). Significantly increased hemolysis percentage was observed at 10 μM after 48 hours incubation of erythrocytes with methotrexate. The results of the study suggested that the therapeutical doses (10–15 μM) of methotrexate may lead to increase in eryptotic and hemolytic activity of erythrocytes through free radical generation and subsequent calcium entry.
{"title":"Induction of Erythrocyte Membrane Blebbing by Methotrexate-Induced Oxidative Stress","authors":"Tayyba Sattar, K. Jilani, Khalida Parveen, Zahid Mushataq, H. Nawaz, Maham Abdul Bari Khan","doi":"10.1177/15593258221093853","DOIUrl":"https://doi.org/10.1177/15593258221093853","url":null,"abstract":"Methotrexate (MTX) is a common chemotherapeutical agent and folate antagonist with reported apoptotic activity in nucleated cells. The presented research work was planned to investigate the eryptotic effects of methotrexate after the exposure of erythrocytes to therapeutical doses (10–15 μM) of methotrexate. Eryptosis and the role of calcium in the stimulation of membrane blebbing were evaluated through the determination of mean cell volume. Oxidative stress induced by methotrexate (10–15 μM) was determined by antioxidative enzyme activities. Cytotoxic activity against human erythrocytes was examined through hemolysis assay. Exposure of erythrocytes to methotrexate results in significant reduction of superoxide dismutase, catalase, and superoxide dismutase activities at 10 and 15 μM in comparison to the untreated cells. Erythrocytes mean cell volume (MCV) was increased after 48 hours exposure of erythrocytes to methotrexate (10 μM). Significantly increased hemolysis percentage was observed at 10 μM after 48 hours incubation of erythrocytes with methotrexate. The results of the study suggested that the therapeutical doses (10–15 μM) of methotrexate may lead to increase in eryptotic and hemolytic activity of erythrocytes through free radical generation and subsequent calcium entry.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42759037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective To determine the effect of the autophagy inhibitor, 3-methyladenine (3-MA), on cognitive function changes, microglia activity, neuronal apoptosis, and inflammation in rats following radiation-induced brain injury. Methods The following groups were established: control, model, and 3-MA. A rat model of radiation-induced brain injury was generated with a medium dose of X-rays. A Morris water maze was used to observe the cognitive function of the rats. H&E staining was used to observe the pathological changes in the hippocampus. The morphological and quantitative changes of neuronal nuclear (NeuN)-positive neurons and Iba-1-positive microglia in the ipsilateral hippocampus were analyzed by immunohistochemistry. Western blot analysis was done to measure the changes of NeuN ionized calcium binding adapter molecule 1(Iba-1) and apoptosis-related proteins. Immunofluorescence staining of Iba-1 and Microtuble-associated protein light chain 3 (LC3) was done to evaluate the changes in microglia autophagy. TUNEL staining was used to detect apoptosis in the hippocampus. Enzyme-Linked Immunosorbent Assay was used to detect the levels of TNF-α and IL-6 as a measure of the inflammatory response in the hippocampus. Results After irradiation, the nucleus of the neurons in the hippocampus was constricted, the pyramidal tract structure was disordered, neuronal apoptosis was increased (P < .001), the expression of microglia increased (P < .01), autophagy was increased (P < .05), and conversion of microglia to the M2 type increased (P < .05). After 3-MA administration, the level of autophagy decreased (P < .05), the damage to the hippocampal region was reduced, neuronal apoptosis decreased (P < .01), and the activity of the microglia decreased (P < .01). Conclusion Radiation can active the Microglia. 3-MA inhibits autophagy and excessive activity in microglia, and promotes the conversion of microglia from the M1 to the M2 type, thereby promoting the recovery of brain tissue following radiation exposure.
{"title":"Effects of 3-Methyladenine on Microglia Autophagy and Neuronal Apoptosis After Radiation-Induced Brain Injury","authors":"Huichao Feng, Yahuan Cui, Jing Liu, Meiying Liu, Wei Zhou, Zhenyu Yan, Haixia Zhang, Y. Wang, Xueming Wang, Xiaomin Liu, Naiyao Chen","doi":"10.1177/15593258221100593","DOIUrl":"https://doi.org/10.1177/15593258221100593","url":null,"abstract":"Objective To determine the effect of the autophagy inhibitor, 3-methyladenine (3-MA), on cognitive function changes, microglia activity, neuronal apoptosis, and inflammation in rats following radiation-induced brain injury. Methods The following groups were established: control, model, and 3-MA. A rat model of radiation-induced brain injury was generated with a medium dose of X-rays. A Morris water maze was used to observe the cognitive function of the rats. H&E staining was used to observe the pathological changes in the hippocampus. The morphological and quantitative changes of neuronal nuclear (NeuN)-positive neurons and Iba-1-positive microglia in the ipsilateral hippocampus were analyzed by immunohistochemistry. Western blot analysis was done to measure the changes of NeuN ionized calcium binding adapter molecule 1(Iba-1) and apoptosis-related proteins. Immunofluorescence staining of Iba-1 and Microtuble-associated protein light chain 3 (LC3) was done to evaluate the changes in microglia autophagy. TUNEL staining was used to detect apoptosis in the hippocampus. Enzyme-Linked Immunosorbent Assay was used to detect the levels of TNF-α and IL-6 as a measure of the inflammatory response in the hippocampus. Results After irradiation, the nucleus of the neurons in the hippocampus was constricted, the pyramidal tract structure was disordered, neuronal apoptosis was increased (P < .001), the expression of microglia increased (P < .01), autophagy was increased (P < .05), and conversion of microglia to the M2 type increased (P < .05). After 3-MA administration, the level of autophagy decreased (P < .05), the damage to the hippocampal region was reduced, neuronal apoptosis decreased (P < .01), and the activity of the microglia decreased (P < .01). Conclusion Radiation can active the Microglia. 3-MA inhibits autophagy and excessive activity in microglia, and promotes the conversion of microglia from the M1 to the M2 type, thereby promoting the recovery of brain tissue following radiation exposure.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45910040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221099281
N. V. Petrova, S. Tarasov, O. Epstein, C. Dubroca, T. Sulpice
Background Nitric oxide (NO) as a vaso- and cardio-protective agent could reduce vasomotor dysfunction in different cardiovascular diseases. One of the current therapeutics targeted at NO availability in the vascular wall are highly diluted antibodies to endothelial NO-synthase (eNOS). This drug has previously shown its endothelium-protective effect and effectiveness in reducing hypertension. Current study was dedicated to evaluate the direct impact of highly diluted antibodies to eNOS on the vessel constriction and dilation ex vivo. Methods For that purpose, we used thoracic aortas dissected from spontaneously hypertensive (SHR) rats. Endothelium-dependent relaxation in the presence of highly diluted antibodies to eNOS (1 mL) was examined after phenylephrine-induced pre-constriction of the aorta rings in response to gradually increased acetylcholine concentration (1 nM to 10 µM). Results Highly diluted antibodies to eNOS enhanced acetylcholine-induced relaxation in a statistically significant manner. Moreover, it was demonstrated that observed effect was similar to perindopril, a well-known angiotensin-converting-enzyme inhibitor, which works through relaxing and widening blood vessels. Conclusions Our findings indicate that highly diluted antibodies to eNOS restored impaired endothelium function, as demonstrated by increased relaxation of SHR rats aorta rings. The revealed results suggest beneficial effect of highly diluted antibodies to eNOS to ameliorate hypertension and related diseases.
{"title":"Highly Diluted Antibodies to eNOS Restore Endothelium Function in Aortic Rings From Hypertensive Rats","authors":"N. V. Petrova, S. Tarasov, O. Epstein, C. Dubroca, T. Sulpice","doi":"10.1177/15593258221099281","DOIUrl":"https://doi.org/10.1177/15593258221099281","url":null,"abstract":"Background Nitric oxide (NO) as a vaso- and cardio-protective agent could reduce vasomotor dysfunction in different cardiovascular diseases. One of the current therapeutics targeted at NO availability in the vascular wall are highly diluted antibodies to endothelial NO-synthase (eNOS). This drug has previously shown its endothelium-protective effect and effectiveness in reducing hypertension. Current study was dedicated to evaluate the direct impact of highly diluted antibodies to eNOS on the vessel constriction and dilation ex vivo. Methods For that purpose, we used thoracic aortas dissected from spontaneously hypertensive (SHR) rats. Endothelium-dependent relaxation in the presence of highly diluted antibodies to eNOS (1 mL) was examined after phenylephrine-induced pre-constriction of the aorta rings in response to gradually increased acetylcholine concentration (1 nM to 10 µM). Results Highly diluted antibodies to eNOS enhanced acetylcholine-induced relaxation in a statistically significant manner. Moreover, it was demonstrated that observed effect was similar to perindopril, a well-known angiotensin-converting-enzyme inhibitor, which works through relaxing and widening blood vessels. Conclusions Our findings indicate that highly diluted antibodies to eNOS restored impaired endothelium function, as demonstrated by increased relaxation of SHR rats aorta rings. The revealed results suggest beneficial effect of highly diluted antibodies to eNOS to ameliorate hypertension and related diseases.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43416803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221100997
Zhenfan Wang, S. He, Minjun Jiang, Xue-Hua Li, Na Chen
Objective To study the radiosensitization effect of curcumin, a natural product with anti-inflammatory and anti-cancer properties, in bladder cancer cells and identify the specific role of FLNA gene in that process. Methods CCK-8 method was initially adopted to identify the proper interventional concentration of curcumin. T24 bladder cancer cells were subjected to CCK-8, flow cytometry, and colony formation assay to study the cell biological behaviors under different interventions. γ-H2AX test was performed to test the level of damage in T24 cells. RT-qPCR and Western blot were conducted to measure FLNA mRNA and protein levels. Results Low-dose curcumin (10, 20 μM) following X-ray exposure resulted in increased DNA damage, augmented apoptosis, and reduced proliferation of T24 cells. Certain radiosensitization was demonstrated when curcumin was applied at 10 μM. Additionally, elevation of FLNA gene and protein levels was also indicated upon combination treatment. Conclusion Low-dose curcumin has certain radiosensitization effect in bladder cancer, where FLNA plays a certain regulatory role.
{"title":"Mechanism Study on Radiosensitization Effect of Curcumin in Bladder Cancer Cells Regulated by Filamin A","authors":"Zhenfan Wang, S. He, Minjun Jiang, Xue-Hua Li, Na Chen","doi":"10.1177/15593258221100997","DOIUrl":"https://doi.org/10.1177/15593258221100997","url":null,"abstract":"Objective To study the radiosensitization effect of curcumin, a natural product with anti-inflammatory and anti-cancer properties, in bladder cancer cells and identify the specific role of FLNA gene in that process. Methods CCK-8 method was initially adopted to identify the proper interventional concentration of curcumin. T24 bladder cancer cells were subjected to CCK-8, flow cytometry, and colony formation assay to study the cell biological behaviors under different interventions. γ-H2AX test was performed to test the level of damage in T24 cells. RT-qPCR and Western blot were conducted to measure FLNA mRNA and protein levels. Results Low-dose curcumin (10, 20 μM) following X-ray exposure resulted in increased DNA damage, augmented apoptosis, and reduced proliferation of T24 cells. Certain radiosensitization was demonstrated when curcumin was applied at 10 μM. Additionally, elevation of FLNA gene and protein levels was also indicated upon combination treatment. Conclusion Low-dose curcumin has certain radiosensitization effect in bladder cancer, where FLNA plays a certain regulatory role.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47943015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221097594
Uzair Nagra, K. Barkat, Muhammad Aleem Ashraf, M. Shabbir
Acyclovir is an antiviral drug that is frequently prescribed for the herpes virus. However, the drug requires frequent dosing due to limited bioavailability (10–26.7%). The rationale of the present study was to develop a self-dissolving microneedle system for local and systemic delivery of acyclovir using a topical lyophilized wafer on microneedle-treated skin to provide the drug at the site of infection. The microneedles prepared with hydroxypropyl methylcellulose (HPMC) (8% w/w) or HPMC (8% w/w)-polyvinyl pyrrolidone (PVP) (30% w/w) penetrated excised rat skin, showing sufficient mechanical strength and rapid polymer dissolution. The topical wafer was prepared with acyclovir (40% w/w; equivalent to 200 mg of drug), gelatin (10% w/w), mannitol (5% w/w), and sodium chloride (5% w/w). The uniform distribution of acyclovir within the wafer in an amorphous form was confirmed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). No polymer–drug interaction was evident in the lyophilized wafer as per Fourier transform infrared spectroscopy (FTIR) analysis. The wafer showed a sufficiently porous structure for rapid hydration as per scanning electron microscopy (SEM) analysis. During ex-vivo analysis, the skin was pre-treated with a self-dissolving microneedle array for 5 minutes, and the wafer was placed on this microporated-skin. Topical wafer provided ∼7–11 times higher skin concentration than the ID99 reported with a lower lag-time. Based on in-vivo testing, ∼2.58 µg/ml of Cmax was achieved in rabbit plasma during 24 hours’ study. Our findings suggest that the self-dissolving microneedle-assisted topical wafer, proposed for the first time, would be efficacious against the infection residing in the skin layer and for systemic therapy.
{"title":"Feasibility of Enhancing Skin Permeability of Acyclovir through Sterile Topical Lyophilized Wafer on Self-Dissolving Microneedle-Treated Skin","authors":"Uzair Nagra, K. Barkat, Muhammad Aleem Ashraf, M. Shabbir","doi":"10.1177/15593258221097594","DOIUrl":"https://doi.org/10.1177/15593258221097594","url":null,"abstract":"Acyclovir is an antiviral drug that is frequently prescribed for the herpes virus. However, the drug requires frequent dosing due to limited bioavailability (10–26.7%). The rationale of the present study was to develop a self-dissolving microneedle system for local and systemic delivery of acyclovir using a topical lyophilized wafer on microneedle-treated skin to provide the drug at the site of infection. The microneedles prepared with hydroxypropyl methylcellulose (HPMC) (8% w/w) or HPMC (8% w/w)-polyvinyl pyrrolidone (PVP) (30% w/w) penetrated excised rat skin, showing sufficient mechanical strength and rapid polymer dissolution. The topical wafer was prepared with acyclovir (40% w/w; equivalent to 200 mg of drug), gelatin (10% w/w), mannitol (5% w/w), and sodium chloride (5% w/w). The uniform distribution of acyclovir within the wafer in an amorphous form was confirmed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). No polymer–drug interaction was evident in the lyophilized wafer as per Fourier transform infrared spectroscopy (FTIR) analysis. The wafer showed a sufficiently porous structure for rapid hydration as per scanning electron microscopy (SEM) analysis. During ex-vivo analysis, the skin was pre-treated with a self-dissolving microneedle array for 5 minutes, and the wafer was placed on this microporated-skin. Topical wafer provided ∼7–11 times higher skin concentration than the ID99 reported with a lower lag-time. Based on in-vivo testing, ∼2.58 µg/ml of Cmax was achieved in rabbit plasma during 24 hours’ study. Our findings suggest that the self-dissolving microneedle-assisted topical wafer, proposed for the first time, would be efficacious against the infection residing in the skin layer and for systemic therapy.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46058895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-01DOI: 10.1177/15593258221103846
Augustine Tandoh, C. Danquah, C. Benneh, D. W. Adongo, Eric Boakye-Gyasi, E. Woode
Studies into drug combination at low doses are a promising approach to the management of pain and inflammation. The aim of this study was to evaluate the anti-edema and anti-hyperalgesic effects of a combination of diclofenac and andrographolide. Male Sprague-Dawley rats were first treated with diclofenac or andrographolide alone (3–100 mg/kg), as well as a combination of the 2 drugs. Carrageenan was then injected into the right hind paw of rats, and changes in paw volume and sensitivity to mechanical (von Frey) and thermal (Hargreaves test) stimuli measured. Results showed drug combination produced synergistic effects at reducing paw edema especially at lower doses, with a Loewe synergy score of 13.02 ± 8.75 in SynergyFinder and a combination index of .41 ± .18 after isobolographic analysis. Again synergy scores for decreasing response to 1.0 and 3.6 g force application of von Frey filaments after drug combination were 10.127 ± 5.68 and 8.554 ± 6.53, respectively, in SynergyFinder. Synergistic effects were also seen after drug combination in the Hargreaves test with a synergy score of 5.136 ± 16.38. In conclusion, combination of diclofenac with andrographolide showed better pharmacologic effects after carrageenan injection and was more synergistic at low-dose combinations.
对低剂量药物组合的研究是治疗疼痛和炎症的一种很有前途的方法。本研究的目的是评估双氯芬酸和穿心莲内酯联合用药的抗水肿和抗痛觉过敏作用。雄性Sprague-Dawley大鼠首先用双氯芬酸或穿心莲内酯单独（3-100 mg/kg）以及这两种药物的组合进行治疗。然后将卡拉胶注射到大鼠的右后爪中，并测量爪体积和对机械（von Frey）和热（Hargreaves试验）刺激的敏感性的变化。结果显示，药物组合在减少爪水肿方面产生协同作用，尤其是在低剂量时，SynergyFinder中的Loewe协同得分为13.02±8.75，等辐射热分析后的组合指数为.41±.18。在SynergyFinder中，药物组合后对1.0 g和3.6 g von Frey细丝施加力的反应降低的协同作用得分分别为10.127±5.68和8.554±6.53。在哈格里夫斯试验中，药物组合后也出现了协同作用，协同作用得分为5.136±16.38。总之，卡拉胶注射后，双氯芬酸与穿心莲内酯的组合显示出更好的药理作用，并且在低剂量组合中具有更强的协同作用。
{"title":"Effect of Diclofenac and Andrographolide Combination on Carrageenan-Induced Paw Edema and Hyperalgesia in Rats","authors":"Augustine Tandoh, C. Danquah, C. Benneh, D. W. Adongo, Eric Boakye-Gyasi, E. Woode","doi":"10.1177/15593258221103846","DOIUrl":"https://doi.org/10.1177/15593258221103846","url":null,"abstract":"Studies into drug combination at low doses are a promising approach to the management of pain and inflammation. The aim of this study was to evaluate the anti-edema and anti-hyperalgesic effects of a combination of diclofenac and andrographolide. Male Sprague-Dawley rats were first treated with diclofenac or andrographolide alone (3–100 mg/kg), as well as a combination of the 2 drugs. Carrageenan was then injected into the right hind paw of rats, and changes in paw volume and sensitivity to mechanical (von Frey) and thermal (Hargreaves test) stimuli measured. Results showed drug combination produced synergistic effects at reducing paw edema especially at lower doses, with a Loewe synergy score of 13.02 ± 8.75 in SynergyFinder and a combination index of .41 ± .18 after isobolographic analysis. Again synergy scores for decreasing response to 1.0 and 3.6 g force application of von Frey filaments after drug combination were 10.127 ± 5.68 and 8.554 ± 6.53, respectively, in SynergyFinder. Synergistic effects were also seen after drug combination in the Hargreaves test with a synergy score of 5.136 ± 16.38. In conclusion, combination of diclofenac with andrographolide showed better pharmacologic effects after carrageenan injection and was more synergistic at low-dose combinations.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"20 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41339117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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