study of possible pro-oxidant and apoptotic effects of hyperhomocysteinemia on rat kidney and the influence of folic acid supplementation

ABSTRACT

Although kidney dysfunction is an important risk factor causing hyperhomocysteinemia [HHcy], recent evidence documents direct role of HHcy in glomerular and interstitial damage. However, the mechanism mediating these pathogenic renal effects of HHcy is poorly understood. In the present study, we hypothesized that if HHcy induced DNA damage and apoptosis that was dependent on oxidative stress, folic acid supplementation would have a major preventive effect. The study was carried out on [20] albino rats classified into 2 groups each including ten animals. Folate-free group [FF] that were fed folatedeficient diet and folate-supplemented group [FS] that were supplemented with folic acid [8 mg / Kg diet] . The feeding of animals continued for 4 weeks after which, blood samples were collected for estimation of folate, homocysteine [Hcy], urea and creatinine. Then, the animals were scarified and kidneys were removed. Kidney homogenates were used for measurement of renal oxidative stress markers including renal malondialdehyde [MDA] and reduced glutathione [GSH]; in addition to renal caspase-3 activity as an apoptotic marker. The results showed that HHcy was confirmed in FF group, with higher MDA and lower GSH levels in renal tissues as compared with FS group. Also, renal Caspase 3 activity was significantly elevated in FF group compared with FS group. Significant correlations were detected between plasma Hcy, plasma folic acid, renal oxidative stress markers and renal caspase 3 activity. It was concluded that dietary folate deprivation either directly or secondary to elevated plasma Hcy concentrations increased susceptibility of renal tissue to lipid peroxidation associated with enhanced apoptotic activity. Thus, Folate supplementation is warranted as it could have a protective effect on kidney either directly or via ameliorating HHcy