Melatonin prevents kidney injury in a high salt diet-induced hypertension model by decreasing oxidative stress

Melatonin, a potent antioxidant molecule, plays a role in blood pressure regulation. We hypothesized that melatonin may generate a protective effect in a high salt diet (HSD) rodent model mediated by decreasing renal oxidative stress. Dahl salt-sensitive rats were divided into three groups according to diet: normal chow (control); HSD; HSD with melatonin [30/mg/kg/day]) placed in their water (HSD + Mel) over an 8-wk period. Blood pressure was measured by the tail cuff method. Kidney injury was evaluated by 24 H urine protein excretion. Glomerular injury index (GII) (fibrotic glomeruli/100 glomeruli) was evaluated from a Masson's trichrome-stained section. Kidney oxidative stress was determined by superoxide production via dihydroethidium staining. Expression of oxidative stress-related genes was measured by reverse transcriptase-qPCR. Melatonin had no effect on blood pressure increase induced by HSD and attenuated proteinuria induced by HSD (HSD -50.7 +/- 12, HSD + Mel - 22.3 +/- 4.3, controls - 6.5 +/- 1.0 gram protein/gram creatinine, P < 0.001). HSD-induced glomerular damage was significantly diminished by melatonin (GII in HSD - 24 +/- 6, HSD + Mel - 3.6 +/- 0.8, controls - 0.8 +/- 0.5, P < 0.05). Superoxide production was significantly higher in kidneys of HSD fed rats than the controls (99 +/- 9 versus 60 +/- 7 relative fluorescent units (RFU)/mu m(2), respectively, P < 0.05). Melatonin also decreased superoxide production (74 +/- 5 RFU/mu m(2), P < 0.05). The expression of kidney inducible nitric oxide synthase and p67(phox) mRNA was significantly higher in HSD than in the controls and HSD + Mel rats. Treatment with melatonin eliminated the deleterious effect of HSD in the kidneys of Dahl salt-sensitive rats. The beneficial effect of melatonin is not mediated by lowering blood pressure but by a direct antioxidative effect.