The effect of aryl hydrocarbon receptor ligands on gentamicin-induced nephrotoxicity in rats.

Polycyclic aromatic hydrocarbons (PAHs)/aryl hydrocarbon receptor (AhR) regulate the expression of target genes, including drug transporter genes which harbor xenobiotic response element (XRE) in their promoter regions. Thus, PAHs/AhR could alter the toxicokinetic profile of many nephrotoxic drugs, including aminoglycosides. In the current study, we investigated the expression and localization of AhR and megalin in rat kidney. Furthermore, we investigated whether AhR and its ligands could modulate the expression of megalin and consequently the gentamicin-induced nephrotoxicity (GN) in rats. Both megalin and AhR receptors are expressed in the proximal tubules of the rat kidney. Treatment with AhR agonist benzo(a)pyrene aggravated GN as indicated by a significant increase in serum creatinine, BUN, KIM1, NAGL, CD-86, and urinary albumin/creatinine ratio. On the other hand, treatment with AhR antagonist resveratrol ameliorated GN as manifested by a pronounced decrease in the aforementioned parameters. The effects of AhR ligands on GN were associated with altered expression of megalin receptor.

Association of irisin and FNDC5 rs16835198 G>T gene polymorphism with type 2 diabetes mellitus and diabetic nephropathy. An Egyptian pilot study.

Diabetes mellitus is a fast-growing health problem in Egypt affecting morbidity, mortality and health care resources. Irisin, a new exercise-induced myokine inducing browning of white adipose tissues, has gained a great interest as a potential new target for combating type 2 diabetes mellitus (T2DM) and its complications. In this study, we assessed serum irisin levels in T2DM and diabetic nephropathy to elucidate possible relationships between irisin and metabolic parameters and renal functions. We also investigated, for the first time in Egypt, the association of FNDC5 rs16835198 G>T polymorphism with T2DM, diabetic nephropathy and irisin levels. One hundred type 2 diabetic patients (40 normoalbuminuric and 60 with nephropathy) as well as fifty control subjects were enrolled in this study. Serum irisin and insulin were evaluated by ELISA. Genomic DNA was genotyped for FNDC5 rs16835198 polymorphism using TaqMan genotyping assay. Serum irisin levels were lower in diabetic patients compared to controls and this decrease was more pronounced in diabetic nephropathy. Irisin correlates with metabolic parameters and renal functions. Frequencies of T allele and TT genotype were significantly lower among T2DM and diabetic nephropathy patients compared to controls. Moreover, G allele was associated with elevated insulin resistance and dyslipidemia without effect on circulating irisin levels. IN CONCLUSION: T2DM and diabetic nephropathy are associated with decreased levels of irisin. FNDC5 rs16835198 TT genotype associates with decreased risk of T2DM in Egyptians with no effect on renal complications. Also, G allele has insulin desensitizing action with no association with circulating irisin levels.