Abstract 551: Melatonin Prevents Renal Injury in a High Salt Diet Induced Hypertension Model by Decreasing Oxidative Stress.

Abstract

Oxidative stress plays an important role in the pathogenesis of target organ damage (TOD) in hypertension, including renal injury. There is evidence, from human and animals' models, that melatonin is involved in the regulation of blood pressure (BP) and may protect from development of high BP and TOD . Melatonin is one of the potent antioxidant molecules in nature. We hypothesized that melatonin protective effect in a high salt diet (HSD) rodent model is mediated by decreasing oxidative stress. Ten Dahl salt sensitive (DSS) rats were fed normal chow [control (Ctrl)], 10 were fed HSD and 10 were fed HSD and got melatonin (Mel) (30/mg/kg/day) in their water for 8 weeks. Body and kidneys weights were measured at the end of the treatment. Renal function was evaluated by measurement of 24 hours urine protein excretion (n=8-10). Glomerular injury index (GII) (fibrotic glomerulus/ 100 glomerulus) was evaluated in Masson's trichrom stained section of renal cortex (n=5). Oxidative stress in the kidneys was evaluated by determining superoxide production using dihydroethidium (DHE) staining (n=5). Melatonin prevents weight loss caused by HSD (Ctrl-398±8, HSD- 335±17 Mel- 372±7 gr. P<0.05 HSD vs. Ctrl and Mel) but not the renal hypertrophy (Ctrl-0.58±0.02, HSD- 0.87±0.04 Mel- 0.9±0.03 gr. /tibia length, p<0.05 Ctrl vs. HSD and Mel). Melatonin decreased the proteinuria seen in HSD fed rats (HSD- 50.7±12 Mel- 22.3±4.3 Protein/Cr, p<0.05). Glomerular damage was significantly higher in the HSD group (GII 24±6) than in Ctrl group (GII 0.8±0.5, p<0.05). Melatonin diminished significantly this damage (GII 3.6±0.8, p<0.05). Superoxide production was significantly higher in kidneys of HSD fed rats than in the Ctrl rats (99±9 vs. 60±7 relative fluorescent units (RFU)/μm 2 , respectively, p<0.05).Treatment with melatonin decreased superoxide production in the kidneys of HSD fed rats(74±5 RFU/ μm 2 , p<0.05 vs. Ctrl and HSD). Treatment with melatonin abolishes the deleterious effect of HSD on the kidneys of HSD fed rats. Melatonin beneficial effect may be mediated by its anti-oxidative properties.