Morin Attenuates Diclofenac-Induced Hepatocellular Death Injury via Nrf2/Ho-1/NQO1, Beclin-1/LC3A/LC3B and p53/Bax/Caspase Signalling Pathways

Abstract

Diclofenac (DF), a nonsteroidal and anti-inflammatory drug, has limited use due to its adverse effects on the liver. On the other hand, morin, a bioflavonoid, has biological and pharmacological properties. This study aims to investigate whether morin may protect against diclofenac-induced liver toxicity. For this purpose, morin (50 or 100 mg/kg) treatment was given orally to the rats for 5 days, and DF (50 mg/kg) was administered intraperitoneally on the 4th and 5th days of the study. Molecular, biochemical, immunohistochemical and histological methods were used to investigate cyclooxygenase enzymes, oxidative stress, apoptosis and autophagy in liver tissue. According to the data obtained, it was observed that DF caused oxidative stress, autophagy and apoptosis damage in liver tissues. Morin showed antioxidant properties, causing a decrease in MDA in hepatic tissue, an increase in the activities of endogenous antioxidants (glutathione peroxidase, superoxide dismutase and catalase) and GSH, HO-1, Nrf2 and NQO1 mRNA levels. Moreover, morin reversed the changes in the levels of apoptotic and autophagic parameters such as bax, bcl-2, cytochrome c, p53, Apaf-1, caspase-3, caspase-6, caspase-9, beclin-1, LC3A, LC3B, MAPK14, MAP15, JNK. When the histopathological analysis results were examined, degenerative changes occurred in the livers of rats administered DF, while morin administration showed a morphological structure close to the control group. As a result, it was determined that oxidative stress, autophagy and apoptosis caused by DF were suppressed by morin, thus protecting the liver tissue from damage.