Abdelrazek Farid, Salama Dawlat A, Alharthi Afaf, Asiri Saeed A, Khodeer Dina M, Qarmush Moath M, Mobasher Maysa A, Ibrahim Mervat
Biochemistry Department, Faculty of Agriculture, Ain Shams University, Cairo 11566, Egypt.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia.
Toxics. 2022 May 23;10(5):271. doi: 10.3390/toxics10050271.
Lead (Pb) is a widespread and nondegradable environmental pollutant and affects several organs through oxidative mechanisms. This study was conducted to investigate the antioxidant protective effect of glycine betaine (GB) against Pb-induced renal and hepatic injury. Male albino rats ( = 45) were divided into three groups: G1 untreated control, G2 Pb-acetate (50 mg/kg/day), and G3 Pb-acetate (50 mg/kg/day) plus GB (250 mg/kg/day) administered for 6 weeks. For G3, Pb-acetate was administered first and followed by GB at least 4 h after. Pb-acetate treatment (G2) resulted in a significant decrease in renal function, including elevated creatinine and urea levels by 17.4% and 23.7%, respectively, and nonsignificant changes in serum uric acid levels. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphates (ALP) activities were significantly increased with Pb treatment by 37.6%, 59.3%, and 55.1%, respectively. Lipid peroxidation level was significantly increased by 7.8 times after 6 weeks of Pb-acetate treatment. The level of reduced glutathione (GSH-R) significantly declined after Pb-acetate treatment. Pb-acetate treatment also reduced the activities of superoxide dismutase (SOD), glutathione-S-transferase (GST), and glutathione peroxidase (GSH-PX) by 74.1%, 85.0%, and 40.8%, respectively. Treatment of Pb-intoxicated rats with GB resulted in a significant reduction in creatinine, urea, ALT, AST, and lipid peroxidation, as well as a significant increase in the level of GSH-R and in the activities of ALP, SOD, GST, and GSH-PX. The molecular interaction between GB and GSH-PX indicated that the activation of GSH-PX in Pb-intoxicated rats was not the result of GB binding to the catalytic site of GSH-PX. The affinity of GB to bind to the catalytic site of GSH-PX is lower than that of HO. Thus, GB significantly mitigates Pb-induced renal and liver injury through the activation of antioxidant enzymes and the prevention of Pb-induced oxidative damage in the kidney and liver.
铅（Pb）是一种广泛存在且不可降解的环境污染物，可通过氧化机制影响多个器官。本研究旨在探讨甘氨酸甜菜碱（GB）对铅诱导的肾和肝损伤的抗氧化保护作用。将45只雄性白化大鼠分为三组：G1为未处理的对照组，G2为醋酸铅（50毫克/千克/天）组，G3为醋酸铅（50毫克/千克/天）加GB（250毫克/千克/天）组，给药6周。对于G3组，先给予醋酸铅，至少4小时后再给予GB。醋酸铅处理（G2组）导致肾功能显著下降，肌酐和尿素水平分别升高17.4%和23.7%，血清尿酸水平无显著变化。铅处理后，血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和碱性磷酸酶（ALP）活性分别显著升高37.6%、59.3%和55.1%。醋酸铅处理6周后，脂质过氧化水平显著升高7.8倍。醋酸铅处理后，还原型谷胱甘肽（GSH-R）水平显著下降。醋酸铅处理还使超氧化物歧化酶（SOD）、谷胱甘肽-S-转移酶（GST）和谷胱甘肽过氧化物酶（GSH-PX）活性分别降低74.1%、85.0%和40.8%。用GB处理铅中毒大鼠可使肌酐、尿素、ALT、AST和脂质过氧化显著降低，同时GSH-R水平以及ALP、SOD、GST和GSH-PX活性显著升高。GB与GSH-PX之间的分子相互作用表明，铅中毒大鼠中GSH-PX的激活并非GB与GSH-PX催化位点结合的结果。GB与GSH-PX催化位点结合的亲和力低于HO。因此，GB通过激活抗氧化酶以及预防铅诱导的肾和肝氧化损伤，显著减轻了铅诱导的肾和肝损伤。
