Kaur Tajpreet, Singh Damanpreet, Pathak Devendra, Singh Amrit P, Singh Balbir
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.
Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, India.
J Biochem Mol Toxicol. 2021 Nov;35(11):e22892. doi: 10.1002/jbt.22892. Epub 2021 Aug 19.
Rhabdomyolysis is a clinical syndrome caused by damage to skeletal muscle, which consequently releases breakdown products into circulation and causes acute kidney injury (AKI) in humans. Intramuscular injection of glycerol mimics rhabdomyolysis and associated AKI. In this study, we explored the role of umbelliferone against glycerol-induced AKI in rats. Kidney function was assessed by measuring serum creatinine, urea, electrolytes, and microproteinuria. Renal oxidative stress was quantified using thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione assay. Renal histological changes were determined using periodic acid Schiff and hematoxylin-eosin staining, and immunohistology of apoptotic markers (Bax, Bcl-2) was done. Serum creatine kinase was quantified to assess glycerol-induced muscle damage. Umbelliferone attenuated glycerol-induced change in biochemical parameters, oxidative stress, histological alterations, and renal apoptosis. Pretreatment with bisphenol A diglycidyl ether, a peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist, attenuated umbelliferone-mediated protection. It is concluded that umbelliferone attenuates glycerol-induced AKI possibly through PPAR-γ agonism in rats.
横纹肌溶解症是一种由骨骼肌损伤引起的临床综合征，骨骼肌损伤会将分解产物释放到循环系统中，进而导致人类急性肾损伤（AKI）。肌肉注射甘油可模拟横纹肌溶解症及相关的急性肾损伤。在本研究中，我们探究了伞形酮对甘油诱导的大鼠急性肾损伤的作用。通过测量血清肌酐、尿素、电解质和微量蛋白尿来评估肾功能。使用硫代巴比妥酸反应性物质、超氧阴离子生成和还原型谷胱甘肽测定法对肾脏氧化应激进行定量分析。使用过碘酸希夫染色和苏木精 - 伊红染色确定肾脏组织学变化，并对凋亡标志物（Bax、Bcl - 2）进行免疫组织学检测。对血清肌酸激酶进行定量分析以评估甘油诱导的肌肉损伤。伞形酮减轻了甘油诱导的生化参数变化、氧化应激、组织学改变和肾脏细胞凋亡。用双酚A二缩水甘油醚（一种过氧化物酶体增殖物激活受体 - γ（PPAR - γ）拮抗剂）进行预处理可减弱伞形酮介导的保护作用。研究得出结论，伞形酮可能通过在大鼠中激活PPAR - γ来减轻甘油诱导的急性肾损伤。
