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

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

Study of the possible oxidative effect of ovariectomy on bone and the protective role of exercise in rats

There is increasing evidence suggesting the role of free radicals in bone resorption and bone loss. Ovariectomized rats have been used as animal models for the study of osteoporosis. Oxidative stress due to reactive oxygen species [ROS] can cause oxidative damage to cells. Even though, there are studies suggesting the role of free radicals in bone loss, however, the preventive role of exercise on oxidative stress remains obscure. The aim of the present study was to investigate the impact of ovariectomy [OVX] on bone and the possible effects of swim-training regimen on the bone turnover markers and oxidant/antioxidant system in adult rats. The present study was carried out on thirty female albino rats classified into 2 groups. Group I [n=10] underwent sham operation, while group II [n=20] underwent bilateral Ovariectomy [OVX]. Eight weeks after OVX, 10 rats of group 2 [group II a] were left for free cage movement while the other 10 rats [group II b] started to practice swim-training regimen for 1 hour daily, 5 days per week, for 7 weeks. Fifteen weeks from the start of the experiment, blood and urine samples were taken for estimation of biochemical markers of bone turnover [calcium, phosphorous, alkaline phosphatase [ALP], Osteocalcin [OC] and urinary deoxypyridinoline [DPD]]. Then, the rats were killed and the femora were removed. The bone tissue homogenates were used for the estimation of oxidant/antioxidant system markers [superoxide dismutase [SOD], glutathione peroxidase [GPx], malondialdehyde [MDA] and hydrogen peroxide [H2O2]]. The results showed that OVX induced bone oxidative stress with in- creased levels of MDA and H2O2 associated with decreased activity of SOD and GPx significantly when compared to control sham-operated rats. Serum ALP, OC and urinary DPD were elevated significantly in the sedentary OVX rats compared to the sham-operated control rats. Swimming exercise improved OVX-induced bone oxidative stress with significantly lower levels of MDA and H2O2 associated with higher levels of SOD and GPx in exercised rats when compared to sedentary OVX rats. Similarly, exercise limited OVX-induced increase in bone turnover by suppression of serum ALP, OC, and urinary DPD levels. It was concluded that OVX in rats induced bone oxidative stress with increased bone turnover and altered its biochemical markers. Short-term swimming exercise for 7 weeks partially stabilized bone turnover and improved oxidative stress but not able to fully reverse the abnormalities induced by OVX. Further researches are indicated to detect the effect of long-term exercise especially on bone mineral content and density