Hepatoprotective activity of herbal extracts and other compounds against acetaminophen-induced hepatotoxicity by various mechanisms: A narrative review

Paracetamol (Acetaminophen) toxicity has become an important problem worldwide. Overdoses and doses close to the usual therapeutic doses can cause acute hepatic failure. Strategies for investigating the biochemical and molecular mechanisms underlying paracetamol toxicity could provide significant benefits in treating paracetamol-induced hepatotoxicity. This review provides an innovative perspective on the role of cytochrome P450 (CYP), oxidative stress, free radicals, JNK, UDP-glucuronosyl transferase, glucuronic acid, sulfotransferase, quinone reductase, caspases, PTP1B, hepatic resident macrophages, kupffer cells, Bax/Bcl-2, mitochondrial oxidative stress, mitochondrial permeability, cytochrome c, p53, Ca2+ channels, necrosome, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, TRPM2 channels, lipid peroxidation, PARP receptors, iNOS, Nrf-2 protein, inflammation, 1-adrenoceptors, NF -KB, connexin 32, coagulation system, and liver X receptor in paracetamol-induced hepatotoxicity. Inhibitors/blockers of CYP2E1, JNK, caspase, PTP1B, Bax/Bcl-2, cytochrome c release, P53, Ca2+ channels, PARP, iNOS, 1-adrenoceptor, connexin 32, and activators of quinone reductase, UDP-glucuronosyl transferase, sulfotransferase, glutathione-S-transferase, glutathione reductase, TRPM2, Nrf-2 protein, and inactivators of hepatic resident macrophages, kupffer cells, necrosome, glutathione peroxidase, NF -KB, and cysteine prodrugs, antioxidants, free radical scavengers, anti-inflammatory agents, anticoagulants, liver X receptor agonists, and compounds that provide/converted into glucuronic acid are used treating paracetamol -induced hepatotoxicity.