Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：庆大霉素引起的肾毒性限制了其作为有效抗菌药物的广泛使用。氧化应激,炎性细胞因子和凋亡细胞死亡是庆大霉素诱导的肾毒性的主要参与者.因此，我们,调查二氢杨梅素(DHM)抗氧化剂和抗炎类黄酮，可以防止庆大霉素的肾毒性作用。
方法：雄性Wistar大鼠给予庆大霉素（100mg/kg/天，i.p.)8天。DHM（400mg/kg，p.o.）与庆大霉素同时给予8天。对照组接受DHM和庆大霉素的载体。组织病理学检查,在研究结束时进行生化检测和免疫组织化学分析.
结果：用DHM治疗可改善庆大霉素引起的肾功能恶化；血清尿素水平，肌酐和胱抑素-C以及尿Kim-1和NGAL的水平，早期肾损害的敏感指标，被拒绝了。此外,DHM消除了庆大霉素诱导的肾脏形态变化。这些肾保护作用可能是通过减少肾脏庆大霉素的积累来介导的，激活抗氧化酶GSH，SOD和CAT降低脂质过氧化和一氧化氮水平。Further,DHM通过降低核因子-κB（NF-κB）的表达来抑制肾脏炎症和凋亡细胞死亡。TNF-α和caspase-3。这些作用与肾脏SIRT3表达的上调相关。此外，DHM通过增强PAX2表达激活损伤的肾小管细胞的再生和新细胞的替换。
结论：DHM是一个有前途的治疗靶点，可以预防庆大霉素诱导的急性肾损伤，并通过其抗氧化剂帮助肾小管细胞恢复。抗炎和抗凋亡特性。
方法：雄性Wistar大鼠给予庆大霉素（100mg/kg/天，i.p.)8天。DHM（400mg/kg，p.o.）与庆大霉素同时给予8天。对照组接受DHM和庆大霉素的载体。组织病理学检查,在研究结束时进行生化检测和免疫组织化学分析.
结果：用DHM治疗可改善庆大霉素引起的肾功能恶化；血清尿素水平，肌酐和胱抑素-C以及尿Kim-1和NGAL的水平，早期肾损害的敏感指标，被拒绝了。此外,DHM消除了庆大霉素诱导的肾脏形态变化。这些肾保护作用可能是通过减少肾脏庆大霉素的积累来介导的，激活抗氧化酶GSH，SOD和CAT降低脂质过氧化和一氧化氮水平。Further,DHM通过降低核因子-κB（NF-κB）的表达来抑制肾脏炎症和凋亡细胞死亡。TNF-α和caspase-3。这些作用与肾脏SIRT3表达的上调相关。此外，DHM通过增强PAX2表达激活损伤的肾小管细胞的再生和新细胞的替换。
结论：DHM是一个有前途的治疗靶点，可以预防庆大霉素诱导的急性肾损伤，并通过其抗氧化剂帮助肾小管细胞恢复。抗炎和抗凋亡特性。
