Awogbindin Ifeoluwa O, Maduako Ikenna C, Adedara Isaac A, Owumi Solomon E, Ajeleti Akinola O, Owoeye Olatunde, Patlolla Anita K, Tchounwou Paul B, Farombi Ebenezer O
Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Cancer Research and Molecular Biology Laboratory, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Environ Toxicol. 2021 Jan;36(1):67-76. doi: 10.1002/tox.23011. Epub 2020 Aug 28.
The increase in the exposure to carbon nanotubes (CNTs) and their incorporation into industrial, electronic, and biomedical products have required several scientific investigations into the toxicity associated with CNTs. Studies have shown that the metabolism and clearance of multiwalled CNTs (MWCNTs) from the body involve biotransformation in the liver and its excretion via the kidney. Since oxidative stress and inflammation underlines the toxicity of MWCNT, we investigated the ameliorative effect of kolaviron (KV), a natural antioxidant and anti-inflammatory agent, on hepatorenal damage in rats. Exposure to MWCNTs for 15 days significantly increased serum activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase thereby suggesting hepatic dysfunction. Kidney function, which was monitored by urea and creatinine levels, was also impaired by MWCNTs. Additionally, MWCNTs markedly increased myeloperoxidase activity, nitric oxide level, reactive oxygen and nitrogen species, and tumor necrosis factor level in both tissues. However, KV in a dose-dependent manner markedly attenuated MWCNT-induced markers of hepatorenal function in the serum and MWCNT-associated inflammation in the liver and kidney. Also, MWCNTs elicited significant inhibition of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase activities. There was a significant diminution in glutathione level (GSH) and enhanced production of malondialdehyde (MDA) in MWCNTs-exposed rats. KV treatment was able to significantly increase the antioxidant enzymes and enhance the GSH level with a subsequent reduction in the MDA level. Taken together, KV elicited ameliorative effects against hepatorenal damage via its anti-inflammatory and antioxidant properties. Thus, KV could be an important intervention strategy for the hepatorenal damage associated with MWCNTs exposure.
碳纳米管（CNTs）暴露的增加及其在工业、电子和生物医学产品中的应用，促使人们对与CNTs相关的毒性进行了多项科学研究。研究表明，多壁碳纳米管（MWCNTs）在体内的代谢和清除涉及肝脏中的生物转化及其通过肾脏的排泄。由于氧化应激和炎症是MWCNT毒性的基础，我们研究了天然抗氧化剂和抗炎剂可乐维酮（KV）对大鼠肝肾损伤的改善作用。暴露于MWCNTs 15天显著增加了血清中天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶和乳酸脱氢酶的活性，从而提示肝功能障碍。通过尿素和肌酐水平监测的肾功能也受到MWCNTs的损害。此外，MWCNTs显著增加了两种组织中的髓过氧化物酶活性、一氧化氮水平、活性氧和氮物种以及肿瘤坏死因子水平。然而，KV以剂量依赖的方式显著减轻了MWCNT诱导的血清中肝肾功指标以及肝脏和肾脏中与MWCNT相关的炎症。此外，MWCNTs显著抑制了超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽-S-转移酶的活性。在暴露于MWCNTs的大鼠中，谷胱甘肽水平（GSH）显著降低，丙二醛（MDA）的产生增加。KV治疗能够显著增加抗氧化酶并提高GSH水平，随后降低MDA水平。综上所述，KV通过其抗炎和抗氧化特性对肝肾损伤产生了改善作用。因此，KV可能是针对与MWCNTs暴露相关的肝肾损伤的重要干预策略。
