Acetaminophen-induced liver injury in normal and obese rats: comparison of oxidative stress and inflammation in the mechanism of toxicity

Abstract

Background: Obesity is associated with increased tissue and systemic inflammation and oxidative stress. Several experimental and epidemiological studies have demonstrated that acetaminophen has been associated with elevated levels of oxidative stress, which also causes impaired liver functions. The aim of this study is to evaluation of the effect of acetaminophen-induced changes of cytokines and oxidative stress in normal and high-fat diet (HFD)-induced obese rats. Methods: 48 male Wistar rats were randomly divided into six groups: (1) normal diet (ND); (2) ND-low doseacetaminophen (NLDA); (3) ND-high dose-acetaminophen (NHDA); (4) high-fat diet (HFD) (HFD-induced obese rats for 8 weeks); (5) HFD-low dose-acetaminophen (HLDA); (6) HFD-high dose-acetaminophen (HHDA) for 2 weeks. Growth parameters, weights of organ and adipose tissues, serum biochemical parameters, and oxidative stress were measured in normal and obese rats intake various doses of acetaminophen. Results: The data indicated that body weight, perirenal adipose tissue, and epididymal adipose tissue in HFD-low doseacetaminophen (HLDA) and HFD-high dose-acetaminophen (HHDA) groups were significantly decreased as compared to the HFD group. Serum parameter levels of total cholesterol, LDL-cholesterol, aspartate aminotransferase, alanine aminotransferase, interleukin-6, and interleukin-1β in HHDA group was significantly increased as compared to the HFD group. The serum parameter levels of alanine aminotransferase and aspartate aminotransferase in HHDA group was significantly increased as compared to the NHDA group. In the trolox equivalent antioxidant capacity (TEAC) and malondialdehyde (MDA), hepatic TEAC in HLDA and HHDA groups were significantly decreased as compared to the HFD group. Moreover, hepatic and serum levels of MDA in HHDA group was significantly increased as compared to the HFD group. In the hepatic antioxidant enzymatic activities, the levels of glutathione, glutathione reductase, and catalase in HHDA group was significantly decreased as compared to the HFD group. The pathological results show that the scores of portal inflammation and intralobular degeneration and inflammation in HLDA and HHDA groups were significantly increased as compared to NLDA and NHDA groups. These results demonstrated that the intake of acetaminophen can enhance oxidative stress and cause impaired liver functions in rats fed a high-fat diet.