Acetaminophen (
APAP), which is also known as
paracetamol or
N-acetyl-p-aminophenol is a safe and potent drug for
fever,
pain and
inflammation when used at its normal therapeutic doses. It is available as
over-the-counter drug and used by all the age groups. The overdose results in
acute liver failure that often requires
liver transplantation. Current clinical
therapy for
APAP-induced liver toxicity is the administration of N-acetyl-
cysteine (NAC), a sulphydryl compound an approved drug which acts by replenishing cellular
glutathione (GSH) stores in the liver. Over the past five decades, several studies indicate that the safety and efficacy of herbal extracts or
plant derived compounds that are used either as monotherapy or as an adjunct
therapy along with conventional medicines for hepatotoxicity have shown favorable responses.
Phytochemicals mitigate necrotic cell death and protect against
APAP-induced liver toxicityby restoring cellular
antioxidant defense system, limiting oxidative stress and subsequently protecting
mitochondrial dysfunction and
inflammation. Recent experimental evidences indicat that these
phytochemicals also regulate differential gene expression to modulate various cellular pathways that are implicated in cellular protection. Therefore, in this review, we highlight the role of the
phytochemicals, which are shown to be efficacious in clinically relevant
APAP-induced hepatotoxicity experimental models. In this review, we have made comprehensive attempt to delineate the molecular mechanism and the cellular targets that are modulated by the
phytochemicals to mediate the cytoprotective effect against
APAP-induced hepatotoxicity. In this review, we have also defined the challenges and scope of
phytochemicals to be developed as drugs to target
APAP-induced hepatotoxicity.