Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt.
Department of Pathology, Faculty of Medicine, Minia University, Minia, Egypt.
Environ Toxicol Pharmacol. 2018 Mar;58:212-219. doi: 10.1016/j.etap.2018.01.011. Epub 2018 Feb 1.
Cadmium (Cd) intoxication in human occurs through inhalation of cigarette smoke and ingestion of contaminated water and food. We investigated the role of nebivolol (NEB) in Cd induced hepatotoxicity. In our study; NEB was given as (10 mg/kg/d) orally to rats for 6 weeks, in the presence or absence of hepatotoxicity induced by oral administration of Cd (7 mg/kg/d) for 6 weeks. Levels of serum liver enzyme biomarkers; alanine transaminase (ALT), aspartate transaminase (AST) and serum total antioxidant capacity (TAC) were measured. In addition; mean arterial pressure and total cholesterol levels were measured. Hepatic superoxide dismutase (SOD) and malondialdehyde (MDA) were detected. Hepatic histopathological features, inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) immunoexpressions were evaluated. Tumor necrosis factor alpha (TNF-α) and B-cell lymphoma-2 (Bcl-2) mRNA gene expressions were detected using real time-PCR (rt-PCR). Our results showed marked increase in all measured parameters except SOD, TAC, eNOS immunoexpression and Bcl2 mRNA gene expression which decreased in Cd induced hepatotoxicity group. NEB showed marvelous protective effect against Cd induced changes. NEB decreased liver enzymes (ALT and AST), mean arterial pressure, total cholesterol levels, MDA, iNOS immunoexpression and TNF-α gene expression but significantly increased SOD, TAC, eNOS immunoexpression and Bcl-2 gene expression. Moreover; NEB markedly improved the histopathological changes induced by Cd. These findings prove the antioxidant, anti-apoptotic and anti-inflammatory properties of NEB and its protective role in Cd induced hepatotoxicity.
镉（Cd）中毒是通过吸入香烟烟雾和摄入受污染的水和食物而发生在人体中。我们研究了奈必洛尔（NEB）在镉诱导的肝毒性中的作用。在我们的研究中；奈必洛尔以（10mg/kg/d）的剂量口服给予大鼠 6 周，同时存在或不存在口服给予镉（7mg/kg/d）6 周引起的肝毒性。测量血清肝酶生物标志物的水平；丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和血清总抗氧化能力（TAC）。此外；还测量了平均动脉压和总胆固醇水平。检测肝超氧化物歧化酶（SOD）和丙二醛（MDA）。评估肝组织病理学特征、诱导型一氧化氮合酶（iNOS）和内皮型一氧化氮合酶（eNOS）免疫表达。使用实时 PCR（rt-PCR）检测肿瘤坏死因子-α（TNF-α）和 B 细胞淋巴瘤-2（Bcl-2）mRNA 基因表达。我们的结果表明，除 SOD、TAC、eNOS 免疫表达和 Bcl-2mRNA 基因表达降低外，所有测量参数均显著增加，这些参数在镉诱导的肝毒性组中降低。奈必洛尔对镉诱导的变化表现出极好的保护作用。奈必洛尔降低了肝酶（ALT 和 AST）、平均动脉压、总胆固醇水平、MDA、iNOS 免疫表达和 TNF-α基因表达，但显著增加了 SOD、TAC、eNOS 免疫表达和 Bcl-2 基因表达。此外；奈必洛尔显著改善了镉引起的组织病理学变化。这些发现证明了奈必洛尔的抗氧化、抗凋亡和抗炎特性及其在镉诱导的肝毒性中的保护作用。
