Abstract

THE POSSIBLE AMELIORATIVE EFFECT OF SOME DRUGS AGAINST PARACETAMOL INDUCED ACUTE LIVER INJURY

Fatma H. Atiya*, Marwa S. Zaghloul, Manar A. Nader

ABSTRACT

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury and acute liver failure all over the world. Although N-acetylcysteine is approved as the standard antidote, its therapeutic benefit is limited to early administration and moderate cases. This emphasizes the need for alternative hepatoprotective agents. The present study investigated the potential protective effects of ranolazine and sacubitril/valsartan (Entresto) against APAP-induced acute liver injury in mice. Two separate experiments were performed using Swiss albino mice randomly divided into four groups, each group containing 7 mice. Acute liver injury was induced by a single intraperitoneal injection of APAP (500 mg/kg). Ranolazine (150 and 305 mg/kg/day) or sacubitril/valsartan (20 and 60 mg/kg/day) was administered orally for seven days before the APAP dose. Hepatoprotection was evaluated by measuring serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, as well as the hepatic histopathological examination. APAP administration markedly increased serum ALT and AST levels and produced severe hepatic damage. This injury caused hepatocellular necrosis, inflammatory cell infiltration, cytoplasmic vacuolation, and disruption of normal hepatic architecture. Pretreatment with either ranolazine or sacubitril/valsartan significantly attenuated these biochemical and histopathological alterations. Notably, the higher doses provide greater protection than the lower doses. Collectively, these findings demonstrate that both ranolazine and sacubitril/valsartan can modulate APAP-induced acute liver injury and suggest them as therapeutic candidates for the management of drug-induced hepatotoxicity.

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