హెల్త్ & మెడికల్ ఇన్ఫర్మేటిక్స్ జర్నల్

Mechanisms of Detoxification and Anti-Oxidation of Nrf2 ARE Pathway in Isonicotinic Acid Hydrazide-Induced Mouse Liver Injury

Abstract

Zhongrui Zhang ,Lei Song ,Lingyan Zhu ,Shufeng Sun ,Guoying Zheng ,Qi Ren ,Yonghong Xiao ,Fumin Feng *

The regulatory mechanisms of nuclear factor erythroid 2-related factor 2 (Nrf2) mainly include detoxification and antioxidation in the progress of isonicotinic acid hydrazide (INH)-induced liver injury. The interaction and protective effects of these two injury mechanisms have not been reported. In this study, eight Kunming mice were administered with INH via gavage at a dose of 90 mg/kg.d. The mice were then killed for 1 d, 3 d, 5 d, 7 d, 2 w, 3 w, and 4 w, and the control groups received gavage of the same volume of distilled water. The pathological changes of liver tissues and location of Nrf2 in liver cell were observed. The superoxide dismutase (SOD) and malondialdehyde (MDA), as well as the expressions of Nrf2, glutathione S-transferase (GST), and SOD mRNAs and proteins were examined. After drug administration for 1–2 weeks, the SOD (total SOD, Cu-ZnSOD, and MnSOD), GST (GSTA1 and GSTM1), and Nrf2 exhibited trough levels, whereas the MDA content reached the peak. These results suggest that Nrf2 nucleocytoplasmic transport occurred in the experimental groups on the seventh day after administration, and then the expressions of mRNAs and proteins of GSTA1, GSTM1, Cu-ZnSOD, and MnSOD were all upregulated with the activation of the Nrf2-antioxidant responsive element (ARE) pathway.