Abstract
Background. The study was designed to investigate if H2S could inhibit high-salt diet-induced renal excessive oxidative stress and kidney injury in Dahl rats. Methods. Male salt-sensitive Dahl and SD rats were used. Blood pressure (BP), serum creatinine, urea, creatinine clearance rate, and 24-hour urine protein were measured. Renal ultra- and microstructures were observed. Collagen-I and -III contents the oxidants and antioxidants levels in renal tissue were detected. Keap1/Nrf2 association and Keap1 s-sulfhydration were detected. Results. After 8 weeks of high-salt diet, BP was significantly increased, renal function and structure were impaired, and collagen deposition was abundant in renal tissues with increased renal MPO activity, H2O2, MDA, GSSG, and •OH contents, reduced renal T-AOC and GSH contents, CAT, GSH-PX and SOD activity, and SOD expressions in Dahl rats. Furthermore, endogenous H2S in renal tissues was decreased in Dahl rats. H2S donor, however, decreased BP, improved renal function and structure, and inhibited collagen excessive deposition in kidney, in association with increased antioxidative activity and reduced oxidative stress in renal tissues. H2S activated Nrf2 by inducing Keap1 s-sulfhydration and subsequent Keap1/Nrf2 disassociation. Conclusions. H2S protected against high-salt diet-induced renal injury associated with enhanced antioxidant capacity and inhibited renal oxidative stress.
Highlights
Numerous studies have demonstrated that high salt caused hypertension, and resulted in kidney injury [1,2,3,4,5,6,7,8]
The rats in Dahl + NS and SD + NS groups were fed with normal diet and 0.9% normal saline was given via intraperitoneal injection daily; the rats in Dahl + HS and SD + HS groups were fed with the diet containing 8% salt and intraperitoneally injected with 0.9% normal saline every day; the rats in Dahl + HS + NaHS and SD + HS + NaHS group were fed with highsalt diet while 90 μmol/kg NaHS was given by intraperitoneal injection every day [22]; and the rats in SD + HS + HA group were fed with high-salt diet while 12.5 mg/kg HA, an inhibitor of CBS, was given by intraperitoneal injection every day [23]
Compared with the rats of Dahl + NS, blood pressure of rats in Dahl + HS group was significantly increased (P < 0.01, Figure 1(a)); renal function was decreased, as reflected by the reduced creatinine clearance rate (P < 0.01, Figure 1(b)) and the increased content of serum creatinine and serum urea (P < 0.01, Figures 1(c) and 1(d)); compared with the rats of SD + NS group, blood pressure and renal function of SD rats did not change in SD + HS group
Summary
Numerous studies have demonstrated that high salt caused hypertension, and resulted in kidney injury [1,2,3,4,5,6,7,8]. The kidney injury and fibrosis of Dahl rats induced by high salt were reported to be closely related to oxidative stress [8, 9]. Up to now, the mechanisms responsible for highsalt-induced kidney injury have been unclear. The study was designed to investigate if H2S could inhibit high-salt diet-induced renal excessive oxidative stress and kidney injury in Dahl rats. Collagen-I and -III contents the oxidants and antioxidants levels in renal tissue were detected. After 8 weeks of high-salt diet, BP was significantly increased, renal function and structure were and ∙
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