Salama Abeer A A, Mostafa Rasha E, Elgohary Rania
Pharmacology Department, Medical Research And Clinical Studies Institute, National Research Centre, ID:(60014618), Dokki, Cairo, Egypt.
Narcotics, Ergogenics and Poisons Department, Medical Research And Clinical Studies Institute, National Research Centre, Dokki, Cairo, ID:(60014618), Egypt.
Res Pharm Sci. 2022 Jan 15;17(2):153-163. doi: 10.4103/1735-5362.335174. eCollection 2022 Apr.
Kidney diseases impose significant global health challenges. Potassium dichromate (PD) is a heavy metal frequently associated with nephrotoxicity. PD prompts oxidative and inflammatory injuries in renal tissues. L-carnitine is a naturally-occurring amino acid commonly used as a supplement.
Forty rats were randomly allocated into 5 groups. Group 1 (normal) received only saline. Nephrotoxicity was induced in the remaining groups by PD (15 mg/kg; i.p). Group 2 served as a nephrotoxic group. Groups 3-5 received L-carnitine (25, 50, and 100 mg/kg; p.o.), respectively for 4 weeks.
FINDINGS/RESULTS: PD administration resulted in elevated serum creatinine and blood urea nitrogen accompanied by diminished reduced glutathione and elevated malondialdehyde, tumor necrosis factor-alpha, and transforming growth factor-beta renal tissue contents relative to normal rats. PD also produced apoptotic histopathological injuries and down-regulated PI3K/Akt signaling pathway; signifying ongoing apoptosis. In the current work, L-carnitine use in the selected dose levels resulted in improvement of all the aforementioned serum, renal tissue, and histological parameters relative to nephrotoxic rats. L-carnitine up-regulated PI3K/Akt signaling pathway that was down-regulated post PD use.
Collectively, the study highlighted that the possible mechanisms beyond the beneficial effects of L-carnitine are mainly through its antioxidant as well as anti-inflammatory actions. L- carnitine significantly abrogated apoptosis up-regulation of PI3K/Akt signaling pathway and signified restoration of normal renal cell proliferation and functionality.
肾脏疾病给全球健康带来重大挑战。重铬酸钾（PD）是一种常与肾毒性相关的重金属。PD可引发肾组织的氧化和炎症损伤。L-肉碱是一种天然存在的氨基酸，常用作补充剂。
40只大鼠随机分为5组。第1组（正常组）仅给予生理盐水。其余组通过腹腔注射PD（15mg/kg）诱导肾毒性。第2组作为肾毒性组。第3 - 5组分别口服L-肉碱（25、50和100mg/kg），持续4周。
与正常大鼠相比，给予PD后血清肌酐和血尿素氮升高，同时肾组织中还原型谷胱甘肽减少，丙二醛、肿瘤坏死因子-α和转化生长因子-β含量升高。PD还导致凋亡性组织病理学损伤并下调PI3K/Akt信号通路，表明存在持续凋亡。在本研究中，与肾毒性大鼠相比，使用选定剂量水平的L-肉碱可改善上述所有血清、肾组织和组织学参数。L-肉碱上调了PD使用后下调的PI3K/Akt信号通路。
总体而言，该研究强调L-肉碱有益作用的可能机制主要是通过其抗氧化和抗炎作用。L-肉碱显著消除了凋亡，上调了PI3K/Akt信号通路，表明恢复了正常肾细胞增殖和功能。
