Elbaset Marawan A, Mohamed Bassim M S A, Moustafa Passant E, Esatbeyoglu Tuba, Afifi Sherif M, Hessin Alyaa F, Abdelrahman Sahar S, Fayed Hany M
Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt.
Department of Molecular Food Chemistry and Food Development, Institute of Food Science and Human Nutrition, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, Hannover 30167, Germany.
Adv Pharmacol Pharm Sci. 2024 Jan 23;2024:6681873. doi: 10.1155/2024/6681873. eCollection 2024.
This research investigated if pitavastatin (Pita) might protect rats' kidneys against thioacetamide (TAA). By altering the PTEN/AKT/mTOR pathway, pitavastatin may boost kidney antioxidant capacity and minimize oxidative damage. Statins have several benefits, including antioxidant and anti-inflammatory characteristics. The principal hypothesis of this study was that Pita can regulate the miR-93/PTEN/AKT/mTOR pathways, which is thought to be responsible for its renoprotective effects. The experiment divided male rats into four groups. Group 1 included untreated rats as the control. Group 2 included rats which received TAA (100 mg/kg intraperitoneally thrice a week for two weeks) to destroy their kidneys. Groups 3 and 4 included rats which received Pita orally at 0.4 and 0.8 mg/kg for 14 days after TAA injections. Renal injury increased BUN, creatinine, and MDA levels and decreased glutathione (GSH) levels. Pitavastatin prevented these alterations. TAA decreased PTEN and increased miR-93, Akt, -Akt, mTOR, and Stat3 in the kidneys. Pitavastatin also regulated the associated culprit pathway, miR-93/PTEN/Akt/mTOR. In addition, TAA induced adverse effects on the kidney tissue, which were significantly ameliorated by pitavastatin treatment. The findings suggest that pitavastatin can attenuate renal injury, likely by regulating the miR-93/PTEN/Akt/mTOR pathway. This modulation of the pathway appears to contribute to the protective effects of pitavastatin against TAA-induced renal injury, adding to the growing evidence of the pleiotropic benefits of statins in renal health.
本研究调查了匹伐他汀（Pita）是否可以保护大鼠肾脏免受硫代乙酰胺（TAA）的损伤。通过改变PTEN/AKT/mTOR信号通路，匹伐他汀可能增强肾脏抗氧化能力并减少氧化损伤。他汀类药物具有多种益处，包括抗氧化和抗炎特性。本研究的主要假设是，Pita可以调节miR-93/PTEN/AKT/mTOR信号通路，该通路被认为与其肾脏保护作用有关。实验将雄性大鼠分为四组。第1组为未处理的大鼠作为对照。第2组大鼠接受TAA（每周腹腔注射100mg/kg，共三次，持续两周）以损伤其肾脏。第3组和第4组大鼠在注射TAA后，分别以0.4mg/kg和0.8mg/kg的剂量口服Pita，持续14天。肾损伤会导致血尿素氮、肌酐和丙二醛水平升高，谷胱甘肽（GSH）水平降低。匹伐他汀可预防这些变化。TAA降低了肾脏中PTEN的水平，并增加了miR-93、Akt、-Akt、mTOR和Stat3的水平。匹伐他汀还调节了相关的关键信号通路miR-93/PTEN/Akt/mTOR。此外，TAA对肾脏组织产生了不良影响，而匹伐他汀治疗可显著改善这些影响。研究结果表明，匹伐他汀可能通过调节miR-93/PTEN/Akt/mTOR信号通路减轻肾损伤。该信号通路的这种调节作用似乎有助于匹伐他汀对TAA诱导的肾损伤的保护作用，进一步证明了他汀类药物在肾脏健康方面的多效性益处。
