Department of Physiology, Faculty of Medicine, Minia University, Minya, Egypt.
Deraya University, New Minya City, Egypt.
Cell Stress Chaperones. 2020 Mar;25(2):211-221. doi: 10.1007/s12192-019-01055-2. Epub 2020 Feb 22.
Hydrogen sulfide (HS), along with nitric oxide (NO) and carbon monoxide (CO), proved to have renoprotective effects in various renal diseases. Therefore, this study investigated the renoprotective effect of HS, in a renal injury model, and its crosstalk with other gasotransmitters such as CO. Thirty-two adult rats were divided into four groups: control, gentamicin (GEN)-treated, GEN + sodium hydrosulfide (NaHS), and GEN + NaHS + zinc protoporphyrin (ZnPP) groups. GEN was used to induce renal injury, NaHS is a water-soluble HS, and ZnPP is a selective heme oxygenase-1 (HO-1) inhibitor used to inhibit CO synthesis in vivo. NaHS improved kidney functions in the GEN group as evidenced by significantly lower levels of renal injury markers: serum urea, creatinine, uric acid, urinary albumin excretion, and urinary albumin/creatinine. Moreover, NaHS administration to the GEN-treated group significantly lowered renal levels of NO and tumor necrosis factor-α with an increase in total antioxidant, HO-1, and interleukin-10 levels. Furthermore, NaHS administration downregulated the GEN-induced overexpression of the renal inducible nitric oxide synthase (iNOS) and upregulated the suppression of endothelial nitric oxide synthase (eNOS) with improvement in the histological examination and periodic acid Schiff (PAS) staining. However, this improvement in kidney function produced by NaHS was reduced by combination with ZnPP but still improved as compared with the GEN-treated group. The renoprotective effects of HS can be through its effects on renal tissue antioxidants, pro-inflammatory and anti-inflammatory cytokines, and expression of eNOS and iNOS which can be partially dependent on CO pathway via induction of HO-1 enzyme.
硫化氢 (HS) 与一氧化氮 (NO) 和一氧化碳 (CO) 一起，已被证明在各种肾脏疾病中具有肾保护作用。因此，本研究调查了 HS 在肾损伤模型中的肾保护作用，以及其与其他气体递质（如 CO）的相互作用。32 只成年大鼠被分为四组：对照组、庆大霉素 (GEN) 处理组、GEN+硫氢化钠 (NaHS) 组和 GEN+NaHS+锌原卟啉 (ZnPP) 组。GEN 用于诱导肾损伤，NaHS 是一种水溶性 HS，ZnPP 是一种选择性血红素加氧酶-1 (HO-1) 抑制剂，用于体内抑制 CO 合成。NaHS 改善了 GEN 组的肾功能，表现为肾损伤标志物的水平显著降低：血清尿素、肌酐、尿酸、尿白蛋白排泄和尿白蛋白/肌酐。此外，NaHS 给药可降低 GEN 处理组肾脏中 NO 和肿瘤坏死因子-α的水平，同时增加总抗氧化剂、HO-1 和白细胞介素-10 的水平。此外，NaHS 给药可下调 GEN 诱导的诱导型一氧化氮合酶 (iNOS) 的过表达，同时上调内皮型一氧化氮合酶 (eNOS) 的抑制作用，改善组织学检查和过碘酸希夫 (PAS) 染色。然而，NaHS 改善肾功能的作用被与 ZnPP 的联合使用所减弱，但仍比 GEN 处理组有所改善。HS 的肾保护作用可能是通过其对肾组织抗氧化剂、促炎和抗炎细胞因子以及 eNOS 和 iNOS 的表达的影响，这可能部分依赖于通过诱导 HO-1 酶的 CO 途径。
