Investigation of in vivo protective effect of orally administered vitamin E and selenium against gentamicininduced renal and hepatic toxicity

Purpose: To investigate the protective effect of vitamin E (Vit E) and selenium (Se) combination against gentamycin (GM)-induced renal and hepatic toxicity in rats. Methods: Forty-eight male Wistar albino rats were administrated GM at a dose of 80 mg/kg/day, with or without Se (1.5 mg/kg/day), and/or Vit E (250 mg/kg/day) for a period of 4 weeks. Serum samples from each rat were subjected to biochemical analysis for kidney and liver functions, while kidney and liver biopsies were also investigated by histological examination. Results: GM significantly increased serum creatinine, urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and free radicals (p < 0.05). Moreover, GM induced significant histological and ultrastructural alterations in the renal and hepatic tissues of the rats. Exposure to a combination of Vit E and Se did not attenuate the GM-induced toxicity in renal and hepatic tissues. Conclusion: These results suggest that Vit E and Se combination have no significant protective role against GM-induced hepatic and renal toxicity

Allelic frequency of PON1 Q192R, CYP2C19*2 and CYP2C19*17 among Jordanian patients taking clopidogrel

Purpose: To investigate the influence of allelic frequencies of PON1 Q192R, CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the response to clopidogrel among Jordanian patients.Methods: Polymorphisms in CYP2C19 were assessed among 148 patients using PCR-RFLP assay.Results: The CYP2C19*2, CYP2C19*17, and PON1 Q192R allele frequencies were 9.8, 28.72 and 28.7 %, respectively. On the genotyping side, the frequencies of CYP2C19*1/1* and CYP2C19*1/2* were 80.4 and 19.6 %, respectively, but none of the patients had CYP2C19*2/2* genotype. The genotype frequencies CYP2C19*17 were 47.97, 46.62 and 5.41 % for wild-type C-C, heterozygote C-T, and the mutant T-T, respectively. PON1 genotype was 42.7 % for QQ, and 57.8 % for QR. None of the patients had RR genotype.Conclusion: Relative to other populations, the observed allelic frequencies are consistent with the values reported for Caucasian and Middle Eastern populations.Keywords: CYP2C9 polymorphisms, Clopidogrel, Genotype, Allele frequency, PON1 gene

PREDICTORS OF GOOD GLYCEMIC CONTROL AMONG TYPE II DIABETES PATIENTS IN PALESTINE

  Objectives: The aim of this study is to assess glycemic control and its relationship with patient characteristics, health-care system factors, and self-care management in type II diabetes patients.Methods: A retrospective cross-sectional study was conducted among 330 type II diabetes patients who met the inclusion criteria and whose medical records covered a period of 1 year. Data concerning patient characteristics, health-care system factors, self-care management, and available last reading of hemoglobin A1c (HbA1c) were collected through personal interviews and a medical records' review using structured questionnaires and data collection forms. Good glycemic control was defined as HbA1c ≤7%. To assess the results, the Statistical Package for Social Sciences (version 16) was used to undertake descriptive, univariate, and multivariate analyses.Results: The mean±standard deviation age was 60±9.7 years. More than half of the participants were male (51.2%), and the majority had additional chronic diseases (88.5%). Of the total 271 participants whose HbA1c levels have been monitored, 16.7% had good glycemic control. Multivariate analysis showed that unemployment was significantly related to a decreased odds of good glycemic control (odds ratio=0.34; 95% confidence interval=0.12-0.98; p<0.05).Conclusion: The study noted that the proportion of patients with good glycemic control was low, a result comparable to studies from many countries. Further investigation and improvement of inappropriate health-care system factors and self-care management together with educational programs that emphasize the importance of self-care management and the health-care providers' role would be of great benefit in glycemic control

Demand for Pharmacogenomics and Personalized Medicine in the United Arab Emirates

The application of personalized medicine (PM) is rapidly evolving [...

The Functionality of UDP-Glucuronosyltransferase Genetic Variants and their Association with Drug Responses and Human Diseases

UDP-glucuronosyltransferases (UGTs) are phase II drug-metabolizing enzymes that metabolize endogenous fatty acids such as arachidonic acid metabolites, as well as many prescription drugs, such as opioids, antiepileptics, and antiviral drugs. The UGT1A and 2B genes are highly polymorphic, and their genetic variants may affect the pharmacokinetics and hence the responses of many drugs and fatty acids. This study collected data and updated the current view of the molecular functionality of genetic variants on UGT genes that impact drug responses and the susceptibility to human diseases. The functional information of UGT genetic variants with clinical associations are essential to understand the inter-individual variation in drug responses and susceptibility to toxicity

Effect of rosiglitazone on 20-hydroxyeicosatetraenoic acid levels and CYP4F2 expression in HepG2 cells

Purpose: To determine the effect of rosiglitazone on the levels of the cardiotoxic arachidonic acid metabolite, 20-hydroxyeicosatetraenoic acid (20-HETE), in the human liver hepatocellular carcinoma cell line, HepG2. Methods: HepG2 cells were treated with thiazolidinedione rosiglitazone and the mRNA and protein expressions of cytochrome P450 4F2 (CYP4F2) responsible for synthesizing 20-HETE were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The levels of 20-HETE were evaluated using liquid chromatography/mass spectrometry (LC-MS). Results: Rosiglitazone significantly increased the levels of CYP4F2 mRNA and protein when compared with the control group (p < 0.05). This was correlated with significantly increased 20-HETE levels in the culture medium of rosiglitazone-treated cells in a dose-dependent manner (p < 0.05). The PPARγ antagonist, GW9662, significantly repressed the increased production of 20-HETE and CYP4F2 mRNA protein (p < 0.05). Conclusion: Rosiglitazone increases the synthesis of 20-HETE via activation of PPARγ receptor and upregulation of CYP4F2. These findings may provide an additional explanation, at least in part, for the unwanted side effects of rosiglitazone on the cardiovascular system

Sequence analysis of the N-acetyltransferase 2 gene (NAT2) among Jordanian volunteers

The present study aimed to identify the NAT2 haplotypes, linkage disequilibrium, and novel NAT2 genetic variants among Jordanian population. We isolated the genomic DNA from 68 healthy, Arab, unrelated Jordanian volunteers to amplify the protein-coding region of NAT2 gene by polymerase chain reaction (PCR). Then, the amplified PCR products were sequenced using Applied Biosystems Model (ABI3730x1). It is found that the allele frequencies of known NAT2 genetic variants 191G>A, 282C>T, 341T>C, 481C>T, 590G>A, and 803A>G were 0.7, 26.5, 48.5, 35.3, 30.9, and 32.4%, respectively. The NAT2 allele frequencies were generally similar to those of white Europeans but different from those of Asian and African populations. The most common NAT2 haplotype was NAT2*5B with a frequency of 29.3%. According to the NAT2 haplotype frequencies, 72% (95% confidence interval 61.4–82.7%) of the volunteers were slow encoding NAT2 haplotype acetylators. The NAT2*5 represented variants 341T>C and 481C>T were in strong but not complete linkage disequilibrium (D′ = 0.8, r2 = 0.63). In addition, this study found a novel nonsynonymous NAT2 436G>A genetic variant with low frequency (0.7%). However, this novel variant was predicted to be tolerated and not harmful to the NAT2 protein, using in silico prediction tools. It is concluded that the frequency of slow encoding NAT2 haplotype was high among Jordanian volunteers, which may have effects on drug responses and susceptibility to some diseases, such as cancers

Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications

Enzymes in the cytochrome P450 4 (CYP4) family are involved in the metabolism of fatty acids, xenobiotics, therapeutic drugs, and signaling molecules, including eicosanoids, leukotrienes, and prostanoids. As CYP4 enzymes play a role in the maintenance of fatty acids and fatty-acid-derived bioactive molecules within a normal range, they have been implicated in various biological functions, including inflammation, skin barrier, eye function, cardiovascular health, and cancer. Numerous studies have indicated that genetic variants of CYP4 genes cause inter-individual variations in metabolism and disease susceptibility. Genetic variants of CYP4A11, 4F2 genes are associated with cardiovascular diseases. Mutations of CYP4B1, CYP4Z1, and other CYP4 genes that generate 20-HETE are a potential risk for cancer. CYP4V2 gene variants are associated with ocular disease, while those of CYP4F22 are linked to skin disease and CYP4F3B is associated with the inflammatory response. The present study comprehensively collected research to provide an updated view of the molecular functionality of CYP4 genes and their associations with human diseases. Functional analysis of CYP4 genes with clinical implications is necessary to understand inter-individual variations in disease susceptibility and for the development of alternative treatment strategies