A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119992 Moscow, Russia.
Institute of Biochemistry of Biologically Active Substances, NAS of Belarus, 230030 Grodno, Belarus.
Int J Mol Sci. 2022 Oct 14;23(20):12273. doi: 10.3390/ijms232012273.
We investigated the nephroprotective effect of D-panthenol in rhabdomyolysis-induced acute kidney injury (AKI). Adult male Wistar rats were injected with 50% glycerol solution to induce rhabdomyolysis. Animals with rhabdomyolysis were injected with D-panthenol (200 mg/kg) for 7 days. On day 8, we examined AKI markers, renal histology, antioxidant capacity, and protein glutathionylation in kidneys to uncover mechanisms of D-panthenol effects. Rhabdomyolysis kidneys were shown to have pathomorphological alterations (mononuclear infiltration, dilatation of tubules, and hyaline casts in Henle's loops and collecting ducts). Activities of skeletal muscle damage markers (creatine kinase and lactate dehydrogenase) increased, myoglobinuria was observed, and creatinine, BUN, and pantetheinase activity in serum and urine rose. Signs of oxidative stress in the kidney tissue of rhabdomyolysis rats, increased levels of lipid peroxidation products, and activities of antioxidant enzymes (SOD, catalase, and glutathione peroxidase) were all alleviated by administration of D-panthenol. Its application improved kidney morphology and decreased AKI markers. Mechanisms of D-panthenol's beneficial effects were associated with an increase in total coenzyme A levels, activity of Krebs cycle enzymes, and attenuation of protein glutathionylation. D-Panthenol protects kidneys from rhabdomyolysis-induced AKI through antioxidant effects, normalization of mitochondrial metabolism, and modulation of glutathione-dependent signaling.
我们研究了 D-泛醇对肌红蛋白尿引起的急性肾损伤(AKI)的肾保护作用。成年雄性 Wistar 大鼠注射 50%甘油溶液诱导肌红蛋白尿。肌红蛋白尿动物注射 D-泛醇(200mg/kg)7 天。第 8 天,我们检查了 AKI 标志物、肾脏组织学、抗氧化能力和肾脏中的蛋白质谷胱甘肽化,以揭示 D-泛醇作用的机制。肌红蛋白尿肾脏表现出形态学改变(单核细胞浸润、肾小管扩张以及 Henle 环和收集管中的透明栓子)。骨骼肌损伤标志物(肌酸激酶和乳酸脱氢酶)的活性增加,观察到肌红蛋白尿,血清和尿液中的肌酐、BUN 和泛肽酶活性升高。肌红蛋白尿大鼠肾脏组织中的氧化应激迹象,脂质过氧化产物水平升高,抗氧化酶(SOD、过氧化氢酶和谷胱甘肽过氧化物酶)的活性均被 D-泛醇给药缓解。其应用改善了肾脏形态并降低了 AKI 标志物。D-泛醇的有益作用机制与辅酶 A 总水平升高、三羧酸循环酶活性以及谷胱甘肽依赖性信号转导的调节有关。D-泛醇通过抗氧化作用、线粒体代谢的正常化和谷胱甘肽依赖的信号转导的调节来保护肾脏免受肌红蛋白尿引起的 AKI。