Journal of Drug Metabolism and Toxicology最新文献

{"title":"Psychiatric Symptoms in Patients with Chikungunya Fever","authors":"C. Aguiar","doi":"10.4172/2157-7609.1000E141","DOIUrl":"https://doi.org/10.4172/2157-7609.1000E141","url":null,"abstract":"","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88736970","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}

{"title":"Direct and Off-Target Effects of ATP-Sensitive Potassium Channels Opener Diazoxide","authors":"O. Akopova","doi":"10.4172/2157-7609.1000227","DOIUrl":"https://doi.org/10.4172/2157-7609.1000227","url":null,"abstract":"Diazoxide (DZ) is a well-known cardioprotective drug capable of mimicking ischemic preconditioning. Being primarily a pharmacological opener of mitochondrial ATP-sensitive potassium channels (mKATP channels), DZ is known to produce multiple side effects because of its interactions with different cellular targets (such as plasma membrane KATP channels, F0F1 ATP synthase, succinate dehydrogenase and others), capable of confounding an understanding of direct bioenergetic effects of mKATP channels opening in mitochondria. In this review direct and offtarget effects of DZ were discussed. The emphasis was made on molecular basis of DZ interaction with KATP channels and different KATP channels isoforms sensitivity to this drug. The present knowledge on DZ interaction with mKATP channels is outlined as well as DZ interactions with other molecular targets affecting mitochondrial functions and bioenergetics. Conclusion was reached that high sensitivity of mKATP channel to DZ allows for avoiding offtarget effects of this drug in studies on isolated mitochondria, which makes it a useful tool in an appraisal of diverse functional effects of mKATP channel opening.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"172 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2017-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79147007","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}

{"title":"Effect of Clomiphene Citrate on Insulin/IGF-1 and GH Levels in Mice Offspring","authors":"Wejdan M Henawi, M. O. Aljahdali","doi":"10.4172/2157-7609.1000226","DOIUrl":"https://doi.org/10.4172/2157-7609.1000226","url":null,"abstract":"Infertility can cause considerable social, emotional and psychological stress. Ovulatory dysfunction is one of the most common causes of reproductive failure in sub-fertile and infertile women. There are several approaches to ovulation induction therapy for the management of women with ovulatory disorders. Fertility drugs are spreading worldwide fast and therefore many studies have reviewed the association between the use of these drugs and physiological, biochemical and histopathological alterations. The results of present study showed that there were observed effects of Clomiphene citrate (Clomid)® on albino mice offspring’s hormones level. Treating mothers with CC doses 0.2 and 0.3 mg/day caused high increasing and variation in Insulin, Insulin-like Growth factor I (IGF-1) and Growth Hormone (GH) levels comparing to control and between male & female, as was clearly noticed on the new offspring of the treated mothers with CC.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"53 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72589975","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}

{"title":"Epigenome-Wide Association (DNA Methylation) Study of Sex Differences in Normal Human Kidney","authors":"S. Joseph, N. George, Bridgett Green-Knox, T. Nicolson, G. Hammons, B. Word, Shiew-Mei Huang, B. Lyn-Cook","doi":"10.4172/2157-7609.1000225","DOIUrl":"https://doi.org/10.4172/2157-7609.1000225","url":null,"abstract":"Studies have identified epigenetic sex differences in several human tissues and have implicated epigenetic factors in the regulation of tissue-specific expression. Studies have also shown that women and men respond differently to various drugs, thereby influencing the pharmacokinetics, pharmacodynamics, adverse reactions, efficacy, and safety of a drug. Using Illumina Human Methylation450 BeadChip kit, we investigated the influence of sex on DNA methylation patterns in normal human kidneys (16 females and 15 males). We then related the methylome to mRNA expression levels in kidney structure/function and Drug Metabolizing Enzyme and Transporter (DMET) genes (32 females and 59 males). Our findings indicate that 429 methylated sites on autosomal chromosomes had significant sex-specific differences in the normal human kidney. Methylated sites in/near regions associated with DMET genes or with genes involved in renal structure/function and disease were identified for subsequent analysis. Validation of 2 DMETs genes (POR and ABCA3) and 2 renal structure/function/disease genes (LAMA5 and PLAT) exhibited significant sex-specific differences in mRNA expression. Our results highlight sitespecific sexual dimorphisms (epigenetic-based) in normal human kidney. Importantly, we provide a reference methylome for normal human kidney, which may be utilized to improve our understanding of renal disease and assessing the overall safety and effectiveness of a drug in the kidney.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"12 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2017-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84197497","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}

{"title":"Effect of Nandrolone Decanoate (Anabolic Steroid) on the Liver and Kidney of Male Albino Rats and the Role of Antioxidant (Antox-Silymarin) as Adjuvant Therapy","authors":"A. R. Mohammed, G. Al-Galad, Amro A Abd-Elgayd, M. Mwaheb, Hala M Al-hamboly","doi":"10.4172/2157-7609.1000224","DOIUrl":"https://doi.org/10.4172/2157-7609.1000224","url":null,"abstract":"Background and objective: The present study is determining the effect of Nandrolone Decanoate (ND) administration on the liver and kidney of white male albino rats. In addition, study the possible protective effect of administration of Antox and Silymarin on ND. Methods: The sample consisted of 110 male albino rats that divided into eleven groups treated by Nandrolone Decanoate at a dose of 7.93 mg/kg and 11.9 mg/kg then treated by Silymarin or Antox or both for 8 weeks. The variations in the body weight and weight of liver & kidney organs of rats are determined in all different groups in addition to the variation in liver enzymes (ALT-AST), bilirubin level, kidney function tests: Creatinine and blood urea level among different study groups are measured. The present study represents the hepatic and renal histological changes observed among the different groups. Results: The highest increase in liver weight the group was treated by ND low dose while the least value of liver weight noted at group is treated by ND high dose. The combination of Silymarin and Antox with ND at high and low dose showed the best results of liver weight. The highest increase in kidney weight showed at ND high dose group while the best result in reduce the kidney weight showed in rats treated by ND low dose with Antox. The highest increase of liver enzymes showed among ND high dose group while the more decrease in liver enzymes showed in groups treated with the combination of Silymarin and Antox with ND at low and high dose. The highest value showed in the group treated by ND high dose while the more decrease in kidney function tests showed in groups treated by the combination of Silymarin and Antox with ND at low and high dose. Conclusion: The combination of Silymarin and Antox with ND showed the best improvement in liver and renal tissue changes, these means synergistic action to protect the hepato-renal cells against harmful effect of ND by their antioxidant and free radical scavenging activities.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"16 1","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90680912","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}

{"title":"In vivo Safety of Dichloromethane-Methanolic Extract of Allium sativum in Normal Mice","authors":"Kariuki Dm, D. Gaichu, Mburu Dn, M. Ngugi","doi":"10.4172/2157-7609.1000223","DOIUrl":"https://doi.org/10.4172/2157-7609.1000223","url":null,"abstract":"The indiscriminate use of Allium sativum in treatment of various diseases can pose a great danger to various body functions. Assessment of the effect of the extract on haematological and biochemical parameters can be used to explain the blood, liver and kidney related functions. Sub-chronic toxicity evaluation was done by orally administering extracts dissolved in 1% DMSO, using a drenching syringe in doses of 100, 500, 1000 and 200 mg/kg body weights of extract for 28 days. The control group was given DMSO at the same frequency and period. The body weights of both treated and control rats was recorded before, during and at the end of the experiment. The results of this study showed that dichloromethane-Methanolic extract of A. sativum induced significant increase in the levels of red blood cell, haemoglobin and haematocrit across the 100, 500, 1000 and 2000 mg/kg.bw dose levels (p 0.05). The total and differential white blood cell counts also increased significantly at all dose levels (p 0.05). The dichloromethane-Methanolic extract of A. sativum caused a significant increase in the levels of liver functions profiles across the 100, 500 and 2000 mg/kg.bw dose levels (p<0.05). Qualitative phytochemical screening confirmed the presence of various phytochemicals which included alkaloids, flavonoids, steroids, saponins, cardiac glycosides and phenolics. These phytochemicals are understood to play a major role in gene expression, erythropoietin stimulatory, thrombopoietic stimulatory, immune-stimulatory and enzyme activities. Flavonoids, cardiac glycosides and alkaloids are also responsible for the increase in the red blood cell count through their antioxidant properties. Conversely, an increase in saponins may result to a decrease in red blood cell indices. It was therefore concluded that the plant extract, subject to various stipulated assays, is safe at particular doses as indicated by changes in haematological parameters. On the other hand, the study also shows that the plant extract is not safe at high doses as indicated by change in the liver and kidney parameters which showed hepatotoxicity and nephrotoxicity respectively.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"11 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2017-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85173269","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}

{"title":"Acute and Sub-Chronic Oral Toxicity Study of Methanolic Extract of Caesalpinia volkensii (Harms)","authors":"Michael N Musila, D. Ngai, J. W. Mbiri, Shardrack M Njagi, W. Mbinda, Ngugi Mp","doi":"10.4172/2157-7609.1000222","DOIUrl":"https://doi.org/10.4172/2157-7609.1000222","url":null,"abstract":"Medicinal plant Caesalpinia volkensii is used to treat Malaria, conjunctivitis, retinoblastoma, and eyelid swelling as well as gonorrhoea and bilharzia. Animal toxicity information on this plant is limited. This medicinal plant was collected in Embu County in Kenya to evaluate its Acute and sub-chronic toxicity using Wistar rats. The rats were orally administered with different doses of the plants extracts. They were weighed on first day and after every 7 days during treatment with the extract. Signs of toxicity were also observed. After 28 days, the rats were sacrificed and blood samples taken for full hemogram, renal and liver function tests. Weight of internal organs was also recorded. Data was analysed using Minitab statistical software version 17. In acute toxicity studies, C. volkensii extracts did not result to death at extract dose of 2000 mg/kg body weight. In sub-chronic toxicity studies, there was no significance difference in body weight and organ weight among the groups treated with the plant extract (p>0.05). Treatment with extract dose of 1000 mg/kg body weight resulted in significant increase in total bilirubin and aspartate aminotransferase (PE‚0.05). In addition, 100 mg/kg body weight resulted in significant decrease in haemoglobin and haematocrit. Qualitative phytochemical screening confirmed the presence of various phytochemicals which have the ability to protect erythrocytes from oxidative damage as well as erythropoietin stimulatory activities. It was therefore concluded that methanolic leaf extract of C. volkensii is safe for acute oral administration. However, care should be exercised in sub-chronic exposure at 1000 mg/kg body weight and above to avoid liver injury.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"34 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2017-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81057969","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}

{"title":"Use of Diethylone, a New Psychoactive Substance, Associated with Multi-system Toxicity: A Case Report of Two Patients","authors":"A. Pomerleau, D. Hindman, A. Ralston, T. Zahran, Alexandra King, R. Gerona","doi":"10.4172/2157-7609.1000232","DOIUrl":"https://doi.org/10.4172/2157-7609.1000232","url":null,"abstract":"Introduction: New Psychoactive Substances (NPS) is a term used to describe synthetic products that may also be referred to as “designer drugs”, “research chemicals”, or “internet drugs”. As new NPS continue to emerge, drug users are exposing themselves to new chemicals with unknown effects. Case report: We report the cases of two patients who reportedly used “Molly” and developed multi-system toxicity requiring Intensive Care Unit (ICU) admission for several days. Both patients presented with altered mental status and during their hospital course manifested neuromuscular hyperactivity and hemodynamic lability. Both patients also had neuropsychiatric symptoms lasting for days after the critical phase of their hospital course. Laboratory investigation using liquid chromatography-quadrupole time-of-flight mass spectrometry identified diethylone in the substance the patients used, and several predicted diethylone metabolites in their sera. Discussion: Clinical effects associated with diethylone use in humans have not previously been described in the medical literature. Our cases highlight diethylone as a new NPS that can be associated with severe and prolonged toxicity.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"56 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75882927","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}

{"title":"Pharmacokinetic-Pharmacodynamic Analyses of Anti-diabetes, Glimepiride: Comparison of the Streptozotocin-Induced Diabetic, GK and Wistar Rats","authors":"A. Kiriyama, Shunsuke Kimura, Chizuki Banba, Miki Yamakawa, R. Yajima, Akino Honbo, K. Iga","doi":"10.4172/2157-7609.1000229","DOIUrl":"https://doi.org/10.4172/2157-7609.1000229","url":null,"abstract":"Efficacy and safety of a drug and its plasma concentration are closely correlated, and plasma concentrations are used as an index of the drug’s effects. Therefore, it is important to understand the relationship between the drug’s plasma concentration and its effects. Plasma glucose control of diabetics retards its progression and glimepiride is widely used for its treatment. In the present study, pharmacokinetic-pharmacodynamic analysis of glimepiride was performed in Wistar rats, with normal plasma glucose levels (Normal), and streptozotocin-induced type 1 diabetes rats (Type 1) and type 2 diabetes GK rats (Type 2). The PK-PD model was structured to investigate time-dependent plasma glucose changes in relation to the plasma concentration, and the PK and PD characteristics of glimepiride were investigated. PK analysis of glimepiride in the three groups showed no significant differences in total body Clearance (CL) and half-life of the β phase. Plasma concentration profiles at a 0.5 mg/kg dose increased in the following order; Type 1, Normal, and Type 2 groups. The area under the plasma concentration-time curves for glimepiride was dosedependent in Normal and Type 2 groups. The CL decreased in the Type 2 group compared to the other groups at a 0.5 mg/kg dose. The maximum decrease in the plasma glucose level was increased in the following order; Normal, Type 2, and Type 1. From the estimated PK-PD analysis, the plasma glimepiride concentration necessary to produce hypoglycemic effects was higher, and the responsiveness of the drug at a drug concentration at the half-maximum effect was quicker, in the Type 2 group compared to the other groups. These effects of glimepiride were considered to improve the pathological condition. This study of the PK-PD characteristics of glimepiride is useful for prediction of the influence of drug-drug interactions and the change in clinical conditions of patients.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"89 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80919915","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}

{"title":"Phenytoin Delayed Excretion because of Esomeprazole Co-administration","authors":"Mostafa Ibrahim Elawady, M. Refaee, Mohamed Sherbash, H. A. Hamad, Ameena Alyazeedi","doi":"10.4172/2157-7609.1000231","DOIUrl":"https://doi.org/10.4172/2157-7609.1000231","url":null,"abstract":"Background: Drug Interaction between Phenytoin and Esomeprazole is not commonly reported or widely recognized. A case of Phenytoin toxicity post prolonged administration of phenytoin and esomeprazole is reported. Case Summary: A 22 years old female diagnosed with MELAS (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, stroke like symptoms). She was maintained on Phenytoin 100 mg suspension via nasogastric tube every 8 hours as anticonvulsant for 3 years and esomeprazole 40 mg via nasogastric tube every 24 hours for hyperacidity. After 7 months from co-administration of phenytoin and esomeprazole the patient developed bradycardia, hypotension with nystagmus so upon checking the phenytoin trough serum level it was found to be 163 μmole/L, phenytoin was suspended and serum level monitored daily but it was found to be increasing to 167 μmole/L and the patient laboratory results showed leukopenia, thrombocytopenia and elevated liver enzymes, upon suspending Esomeprazole it was noticed that the Phenytoin serum level decreased dramatically by 10-20 μmole/L/day so the toxicity symptoms and abnormal laboratory results resolved upon normalization the Phenytoin serum level. Conclusion: Esomeprazole may competitively inhibit the CYP2C19 mediated Phenytoin metabolism which leads to prolonged exposure to high serum level and toxicities.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"128 20 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87764417","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}