The hepatoprotective effects of 𝘔𝘰𝘳𝘪𝘯𝘨𝘢 𝘰𝘭𝘦𝘪𝘧𝘦𝘳𝘢 against antiretroviral-induced cytotoxicity in HepG₂ cells

Abstract

𝗜𝗻𝘁𝗿𝗼𝗱𝘂𝗰𝘁𝗶𝗼𝗻: The untreated human immunodeficiency virus (HIV), a lentivirus species that attacks immune cells, causes acquired immunodeficiency syndrome (AIDS). HIV/AIDS is managed by Antiretroviral therapy (ART). The ART regimen contains nucleoside reverse transcriptase inhibitors (NRTIs) associated with oxidative stress. Medicinal plants are often combined with ART to diminish the side effects of ART use. The 𝘔𝘰𝘳𝘪𝘯𝘨𝘢 𝘰𝘭𝘦𝘪𝘧𝘦𝘳𝘢 (MO) tree extracts have been shown to contain bioactive compounds with antioxidant effects.

𝗔𝗶𝗺: This 𝘪𝘯 𝘷𝘪𝘵𝘳𝘰 study evaluated the cytotoxicity of an NRTI (tenofovir) and its potential amelioration by MO leaf extract.

𝗠𝗲𝘁𝗵𝗼𝗱𝘀: HepG₂ cells were exposed to tenofovir, MO, and combination (tenofovir and MO) treatment groups for 24 and 120 hours. MO aqueous leaf extract was prepared, and cytotoxicity was assessed. Markers for oxidative stress and antioxidant response were assessed using spectrophotometry, luminometry, ELISA, qPCR, and western blotting experimental techniques.

𝗥𝗲𝘀𝘂𝗹𝘁𝘀: At 24 hours, tenofovir decreased MDA 𝘕𝘙𝘍2, 𝘚𝘖𝘋2, 𝘊𝘈𝘛 mRNA, and NRF2, SOD2, and CAT protein expression. It then increased GSH, 𝘎𝘊𝘓𝘊 mRNA and p-NRF2 protein expression. MO decreased GSH levels, NRF2, 𝘎𝘊𝘓𝘊, and 𝘚𝘖𝘋2 mRNA expression and increased 𝘊𝘈𝘛 mRNA, as well as NRF2, p-NRF2, SOD2, and CAT protein expression. At 120 hours, tenofovir increased MDA, NRF2 mRNA, NRF2, p-NRF2, and SOD2 protein expression. It then decreased GSH levels, 𝘎𝘊𝘓𝘊, 𝘚𝘖𝘋2, 𝘊𝘈𝘛 mRNA and CAT protein expression. MO decreased MDA and GSH levels, NRF2 and CAT protein expression. It then increased 𝘕𝘙𝘍2, 𝘎𝘊𝘓𝘊, 𝘚𝘖𝘋2, 𝘊𝘈𝘛 mRNA, p-NRF2, and SOD2 protein expression. The combination treatment group downregulated MDA and upregulated the expression of NRF2, 𝘎𝘊𝘓𝘊, 𝘚𝘖𝘋2, 𝘊𝘈𝘛 mRNA and NRF2, p-NRF2, SOD2, and CAT proteins.

𝗖𝗼𝗻𝗰𝗹𝘂𝘀𝗶𝗼𝗻: Adding MO to tenofovir downregulates reactive oxygen species by upregulating the NRF2-antioxidant pathway to reduce oxidative stress. Therefore, MO has the potential to ameliorate toxicity induced by tenofovir.