Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt.
Life Sci. 2024 Jan 1;336:122318. doi: 10.1016/j.lfs.2023.122318. Epub 2023 Nov 29.
Gentamicin-induced nephrotoxicity limits its widespread use as an effective antibacterial agent. Oxidative stress, inflammatory cytokines and apoptotic cell death are major participants in gentamicin-induced nephrotoxicity. We therefore, investigated whether dihydromyricetin (DHM), the antioxidant and anti-inflammatory flavonoid, could protect against the nephrotoxic effects of gentamicin.
Male Wistar rats administrated gentamicin (100 mg/kg/day, i.p.) for 8 days. DHM (400 mg/kg, p.o.) was concurrently given with gentamicin for 8 days. Control group received the vehicle of DHM and gentamicin. Histopathological examinations, biochemical measurements and immunohistochemical analyses were done at the end of the study.
Treatment with DHM improved the gentamicin induced deterioration of renal functions; serum levels of urea, creatinine and cystatin-C as well as urinary levels of Kim-1 and NGAL, the sensitive indicators for early renal damage, were declined. Additionally, DHM abrogated gentamicin-induced changes in kidney morphology. These nephroprotective effects were possibly mediated via decreasing renal gentamicin buildup, activating the antioxidant enzymes GSH, SOD and CAT and decreasing lipid peroxidation and nitric oxide levels. Further, DHM suppressed renal inflammation and apoptotic cell death by decreasing the expression of nuclear factor-kappa B (NF-κB), TNF-alpha and caspase-3. These effects were correlated to the upregulation of renal SIRT3 expression. Also, DHM activated the regeneration and replacement of injured tubular cells with new ones via enhancing PAX2 expression.
DHM is a promising therapeutic target that could prevent acute renal injury induced by gentamicin and help renal tubular cells to recover through its antioxidant, anti-inflammatory and antiapoptotic properties.
庆大霉素诱导的肾毒性限制了其作为有效抗菌剂的广泛应用。氧化应激、炎症细胞因子和细胞凋亡是庆大霉素诱导肾毒性的主要参与者。因此，我们研究了二氢杨梅素（DHM），一种抗氧化和抗炎的黄酮类化合物，是否可以预防庆大霉素的肾毒性作用。
雄性 Wistar 大鼠给予庆大霉素（100mg/kg/天，腹腔注射）8 天。DHM（400mg/kg，口服）与庆大霉素同时给予 8 天。对照组给予 DHM 和庆大霉素的载体。研究结束时进行组织病理学检查、生化测量和免疫组织化学分析。
DHM 治疗改善了庆大霉素引起的肾功能恶化；血清尿素、肌酐和胱抑素 C 水平以及尿 Kim-1 和 NGAL 水平（早期肾损伤的敏感指标）降低。此外，DHM 减轻了庆大霉素引起的肾脏形态变化。这些肾保护作用可能是通过减少肾脏中庆大霉素的蓄积、激活抗氧化酶 GSH、SOD 和 CAT 以及降低脂质过氧化和一氧化氮水平来介导的。此外，DHM 通过降低核因子-κB（NF-κB）、TNF-α 和 caspase-3 的表达来抑制肾炎症和细胞凋亡。这些作用与肾脏 SIRT3 表达的上调有关。此外，DHM 通过增强 PAX2 表达来激活受损肾小管细胞的再生和替代。
DHM 是一种有前途的治疗靶点，可预防庆大霉素引起的急性肾损伤，并通过其抗氧化、抗炎和抗凋亡特性帮助肾小管细胞恢复。
