TY - JOUR
T1 - Melatonin prevents kidney injury in a high salt diet-induced hypertension model by decreasing oxidative stress
AU - Leibowitz, Avshalom
AU - Volkov, Alexander
AU - Voloshin, Konstantin
AU - Shemesh, Chen
AU - Barshack, Iris
AU - Grossman, Ehud
N1 - Publisher Copyright:
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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)/μm2, respectively, P < 0.05). Melatonin also decreased superoxide production (74 ± 5 RFU/μm2, P < 0.05). The expression of kidney inducible nitric oxide synthase and p67phox 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.
AB - 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)/μm2, respectively, P < 0.05). Melatonin also decreased superoxide production (74 ± 5 RFU/μm2, P < 0.05). The expression of kidney inducible nitric oxide synthase and p67phox 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.
KW - blood pressure
KW - kidney
KW - melatonin
KW - oxidative stress
KW - salt
UR - http://www.scopus.com/inward/record.url?scp=84956843580&partnerID=8YFLogxK
U2 - 10.1111/jpi.12287
DO - 10.1111/jpi.12287
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AN - SCOPUS:84956843580
SN - 0742-3098
VL - 60
SP - 48
EP - 54
JO - Journal of Pineal Research
JF - Journal of Pineal Research
IS - 1
ER -