Metabolism of liver CYP450 and ultrastructural changes after long-term administration of aspirin and ibuprofen

Publication date: December 2018Source: Biomedicine & Pharmacotherapy, Volume 108Author(s): Congcong Wen, Zaishou Zhuang, Huanchun Song, Shuhua Tong, Xianchuan Wang, Yijing Lin, Haichao Zhan, Zhibin Chen, Lufeng HuAbstractWorldwide, aspirin and ibuprofen are the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs). Some adverse reactions, including gastrointestinal reactions, have been concerned extensively. Nevertheless, the mechanism of liver injury remains unclear. In the present study, we focused on the metabolism of liver cytochrome P450 (CYP450) and ultrastructural morphology of liver cells. A total of thirty rats were divided into three groups of 10. Rats in the aspirin and ibuprofen groups were given enteric-coated aspirin (15 mg/kg) and ibuprofen (15 mg/kg), respectively by gavage for four weeks. The body weights were recorded every two days. Liver function and metabolic capacity of CYP450 were studied on days 14 and 28. We then conducted ultrastructural examinations. Body weights in the Ibuprofen group were lower than those of the Control group, and ALT and AST levels were significantly higher (P < 0.05). There were no significant differences in terms of body weight, ALT or AST between the Aspirin and Control groups. The metabolic capacity of CYP450 was evaluated using five probe drugs, phenacetin, tolbutamide, metoprolol, midazolam, and bupropion. We found that ibuprofen and aspirin induced metabolism of the probe drugs. Moreover, according ...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research