Protective effects of linagliptin and tenofovir disoproxil fumarate against APAP-induced acute liver injury: A biochemical, histological, and computational study.

Hepatic injuries are one of the leading threats to public health which can further lead to liver diseases such as liver fibrosis and cirrhosis. An overdose of certain chemicals and drugs can cause hepatotoxicity, which leads to drug-induced liver injury. Linagliptin is an effective drug in treating type 2 diabetes, as it has been shown to reduce oxidative stress. Tenofovir (an antiretroviral) is the first-line treatment for hepatitis B and AIDS; it inhibited the production of reactive oxygen species (ROS) and reduced inflammation. The present research was conducted to assess protective effect of two FDA-approved repurposed (anti-diabetic and antiretroviral) drugs against APAP-induced acute liver injury in mouse models. A multi-model approach was applied by integrating in vivo, in vitro, and silico techniques with histopathological analysis. APAP injection enhanced ALT, AST, ALP, and bilirubin levels. In vivo analysis exhibited ameliorated liver injury with Lina and TDF, as evidenced by significantly lowered liver injury markers. Combination therapy normalized insulin levels, indicating improved glycemic control. Both drugs increased TAC and decreased levels of TOS and MDA. In Silico studies revealed a strong interaction between Lina and TDF with pro-inflammatory receptors, including JNK, TNF-α, and IL-1. Histopathological analysis further proved the reversal of acute liver injury. Together, Lina and TDF acted as multi-target anti-liver injury drugs, indicating their potential as a promising hepato-therapeutic repurposed drug.