title: Melatonin prevents kidney injury in a high salt diet-induced hypertension model by decreasing oxidative stress.
abstract: 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)/μm(2), respectively, P < 0.05). Melatonin also decreased superoxide production (74 ± 5 RFU/μm(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.
authors.affiliation: Internal Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.|Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Avshalom
authors.initials: A
authors.lastname: Leibowitz
authors.affiliation: Institute of Pathology, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Volkov
authors.affiliation: Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Voloshin
authors.affiliation: Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Chen
authors.initials: C
authors.lastname: Shemesh
authors.affiliation: Institute of Pathology, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.affiliation: Internal Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.|Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Grossman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D020303:Rats, Inbred Dahl; D051437:Renal Insufficiency / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017673:Sodium Chloride, Dietary / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D017673:Sodium Chloride, Dietary; D008550:Melatonin
keywords: blood pressure; kidney; melatonin; oxidative stress; salt