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Melatonin prevents kidney injury in a high salt diet‐induced hypertension model by decreasing oxidative stress
Author(s) -
Leibowitz Avshalom,
Volkov Alexander,
Voloshin Konstantin,
Shemesh Chen,
Barshack Iris,
Grossman Ehud
Publication year - 2016
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12287
Subject(s) - melatonin , endocrinology , medicine , oxidative stress , kidney , nitric oxide , nitric oxide synthase , chemistry , superoxide dismutase , biology
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 )/ μ m 2 , respectively, P < 0.05). Melatonin also decreased superoxide production (74 ± 5 RFU / μ 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.