Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Nigeria.
Biochem Biophys Res Commun. 2018 Sep 18;503(4):3167-3173. doi: 10.1016/j.bbrc.2018.08.112. Epub 2018 Aug 24.
The investigation into the potential health risks associated with the use of engineered nanoparticles is a major scientific interest in recent years. The present study elucidated the involvement of pro-inflammatory cytokines, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in carboxylated multi-walled carbon nanotubes (MWCNTs)-induced hepatotoxicity. Pubertal rats were exposed to purified MWCNTs at 0, 0.25, 0.50, 0.75 and 1.0 mg/kg for 5 consecutive days. Results indicated that exposure to MWCNTs caused liver damage evidenced by significant elevation in serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) when compared with control. Moreover, MWCNTs significantly decreased superoxide dismutase (SOD) and glutathione S-transferase (GST) activities as well as glutathione level whereas it significantly increased catalase (CAT) and glutathione peroxidase (GPx) activities in liver of the treated rats. Moreover, the dose-dependent increase in hepatic hydrogen peroxide (HO) and lipid peroxidation levels were accompanied by marked increase in micronucleated polychromatic erythrocytes (MNPCE) in the MWCNTs-treated rats. Administration of MWCNTs significantly increased serum concentrations of pro-inflammatory cytokines namely interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the treated rats. Immunohistochemical analysis showed significantly increased COX-2 and iNOS protein expressions in the liver of MWCNTs-treated rats. In conclusion, carboxylated MWCNTs induces hepatic damage via disruption of antioxidant defense systems, promotion of pro-inflammatory cytokines generation and expression of COX-2 and i-NOS in rats.
近年来，对与工程纳米粒子使用相关的潜在健康风险的调查是一个主要的科学关注点。本研究阐明了促炎细胞因子、环氧化酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）在羧基化多壁碳纳米管（MWCNTs）诱导的肝毒性中的作用。青春期大鼠连续 5 天暴露于 0、0.25、0.50、0.75 和 1.0mg/kg 的纯化 MWCNTs 中。结果表明，与对照组相比，MWCNTs 的暴露导致了肝损伤，表现为血清天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、碱性磷酸酶（ALP）和γ-谷氨酰转移酶（GGT）活性显著升高。此外，MWCNTs 显著降低了超氧化物歧化酶（SOD）和谷胱甘肽 S-转移酶（GST）的活性和谷胱甘肽水平，同时显著增加了肝中过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的活性。此外，MWCNTs 处理大鼠肝中过氧化氢（HO）和脂质过氧化水平的剂量依赖性增加伴随着多色性红细胞微核（MNPCE）的显著增加。MWCNTs 的给药显著增加了处理大鼠血清中促炎细胞因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的浓度。免疫组织化学分析显示，MWCNTs 处理大鼠肝中 COX-2 和 iNOS 蛋白表达显著增加。总之，羧基化 MWCNTs 通过破坏抗氧化防御系统、促进促炎细胞因子的产生以及 COX-2 和 iNOS 的表达，诱导大鼠肝损伤。
