Prophylactic and Ameliorative Effects of PPAR-γ Agonist Pioglitazone in Improving Oxidative Stress, Germ Cell Apoptosis and Inflammation in Gentamycin-Induced Testicular Damage in Adult Male Albino Rats.

Peroxisome proliferator-activated receptor gamma (PPAR-γ) is ubiquitously expressed in testicular tissue and plays a crucial role in regulating various physiological processes. Pioglitazone (PIO) is one of the PPAR-γ agonists, having anti-oxidant and anti-inflammatory effects. Patients on gentamycin treatment may undergo serious side effects such as testicular damage. To the best of our knowledge, this was the first study to investigate the possible protective anti-inflammatory and anti-apoptotic effects of PIO on gentamycin-induced testicular damage. Fifty adult male Wistar albino rats included in the study as the control group (CTL) received normal saline; a gentamycin-induced testicular damage group (GM) received gentamycin (100 mg/kg); PIO5, PIO10, PIO20 groups received PIO at a dose of 5, 10, and 20 mg/ kg, respectively, for 21 days, and gentamycin was started at day 15 of the experiment for 6 days. The parameters of spermatozoa and histopathological alterations in the testes were significantly improved in the PIO20 group. Moreover, MDA levels, inflammatory mediators, and apoptotic Bax expression were decreased. The activity of glutathione peroxidase, catalase, total antioxidant capacity, and anti-apoptotic Bcl-2 genes expression were increased. It was concluded that PIO20 could protect against gentamycin-induced testicular damage in Wistar rats through its anti-oxidant, anti-inflammatory, and antiapoptotic effects.

Association of TNF-α-308 G>A (rs1800629) polymorphism with susceptibility of metabolic syndrome.

BACKGROUND: Metabolic Syndrome (MetS) mainly comprises hyperglycemia, hypertension and dyslipidemia, and has been proven to increase the risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. Studies have suggested that many factors may be involved in the pathogenesis of MetS, but tumor necrosis factor alpha (TNF- α) may play a strong role as its gene polymorphism was associated with insulin resistance and obesity. The aim of this study was to evaluate the possible association of TNF-α-308 G > A (rs1800629) polymorphism with susceptibility of metabolic syndrome. METHODS: a case-control study was conducted upon 128 participants recruited from Suez Canal University Hospital (Ismailia, Egypt), divided into the MetS group (n = 64) and the control group (n = 64). Genotyping of the TNF-α-308 G > A (rs1800629) polymorphism was performed by restriction fragment length polymorphism (PCR-RFLP). RESULTS: The A allele was significantly higher among MetS patients (40%) than controls (11%) (p < 0.0001). A significant association was observed between the healthy and MetS groups under the influence of co-dominant, dominant and over-dominant genetic models (p < 0.05). Also, there were positive correlations between TNF-α-308 (G/A) polymorphism and risk factors of metabolic syndrome like body mass index (BMI); fasting blood sugar; cholesterol and low density lipoprotein (LDL) (p < 0.05). Regression analysis was done for predictors of MetS and the A allele was found to be a strong predictor (OR 2.752; 95% CI = 1.106 to 6.847; p = 0.03), as well as, BMI; triglyceride (TG); high density lipoprotein (HDL); LDL and cholesterol (p < 0.05). CONCLUSIONS: TNF-α-308 G > A (rs1800629) polymorphism may be play an important role in the development of metabolic syndrome and A allele is a strong predictor in Egyptians.

Association of CD40 rs1883832 Polymorphism with Susceptibility of Diabetic Nephropathy and Neuropathy in Egyptian Population.

Diabetic nephropathy (DN) and peripheral neuropathy (DPN) are unpredictable diabetic complications with narrow management alternatives. CD40-CD40 ligand system may be an essential pathway for diabetic microvascular complications. No previous studies had evaluated the relationship between CD40 rs1883832 polymorphism and DN/DPN. This study aimed to investigate the association between CD40 rs1883832 polymorphism and the risk of nephropathy and neuropathy in Egyptian patients with type 2 diabetes mellitus. A total of 106 diabetic patients (53 with nephropathy and 53 with neuropathy) and 53 healthy controls (without DM or other overt chronic conditions) were recruited from Suez Canal University Hospitals. Genotyping of CD40 gene polymorphisms was carried out using the polymerase chain reaction-restriction fragment length polymorphism assay. Patients with TT genotype and T allele carry a higher risk of developing DN (odds ratio (OR)=5.40, P=0.0026) and OR=2.56, P=0.0009, respectively). Likewise, the risk of DPN was significantly higher in patients carrying TT genotype (OR=2.91, P=0.045) and T allele (OR=1.84, P=0.028), respectively. In conclusions, the T allele is significantly associated with DN and DPN. Further studies with larger sample sizes are necessary to confirm our observations.