Hydrogen Sulfide Inhibits High-Salt Diet-Induced Renal Oxidative Stress and Kidney Injury in Dahl Rats

<jats:p><jats:italic>Background</jats:italic>. The study was designed to investigate if H<jats:sub>2</jats:sub>S could inhibit high-salt diet-induced renal excessive oxidative stress and kidney injury in Dahl rats.<jats:italic>Methods</jats:italic>. 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.<jats:italic>Results</jats:italic>. 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, H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>, MDA, GSSG, and<jats:sup>•</jats:sup>OH contents, reduced renal T-AOC and GSH contents, CAT, GSH-PX and SOD activity, and SOD expressions in Dahl rats. Furthermore, endogenous H<jats:sub>2</jats:sub>S in renal tissues was decreased in Dahl rats. H<jats:sub>2</jats:sub>S 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. H<jats:sub>2</jats:sub>S activated Nrf2 by inducing Keap1 s-sulfhydration and subsequent Keap1/Nrf2 disassociation.<jats:italic>Conclusions</jats:italic>. H<jats:sub>2</jats:sub>S protected against high-salt diet-induced renal injury associated with enhanced antioxidant capacity and inhibited renal oxidative stress.</jats:p>