Hepatoprotective, antioxidant, and anti-inflammatory properties of quercetin in paracetamol overdose-induced liver injury in rats

Acute liver injury is a severe clinical condition with potentially fatal consequences commonly caused by viral infections, medications, toxins, and drug overdoses. Among these, paracetamol (acetaminophen) overdose is a leading cause of hepatic failure due to its narrow therapeutic index, resulting in oxidative stress and hepatocyte apoptosis. Quercetin, a flavonoid found abundantly in vegetables and herbs, has demonstrated antioxidant, hepatoprotective, and anti-inflammatory properties. This study evaluates the hepatoprotective role of quercetin in mitigating liver damage induced by paracetamol overdose in an experimental rat model. A total of 28 male rats were randomly divided into four groups (n = 7 per group): (i) normal control (distilled water and saline), (ii) paracetamol-induced liver injury group (2 g/kg paracetamol intraperitoneally), (iii) paracetamol + quercetin group (50 mg/kg quercetin orally and 2 g/kg paracetamol intraperitoneally), and (iv) quercetin-only group (50 mg/kg quercetin intraperitoneally). Blood and liver samples were analyzed for liver enzymes (glutamate pyruvate transaminase [GPT], glutamate oxaloacetate transaminase [GOT]), inflammatory markers (nuclear factor kappa B [NF-κB], tumor necrosis factor-alpha [TNF-α]), apoptotic markers (cysteine-aspartic acid protease 3 [Caspase-3], B-cell lymphoma 2 [BCL2]), oxidative stress markers (malondialdehyde [MDA], glutathione [GSH]), and histological changes. Paracetamol administration significantly elevated GPT, GOT, NF-κB, TNF-α, caspase-3, and MDA levels whereas reducing BCL2 and GSH levels, indicating hepatic injury and oxidative stress. In contrast, results showed that quercetin treatment significantly mitigated these changes, demonstrating its potential hepatoprotective effects. Histological analysis further confirmed that quercetin reduced hepatic damage compared to the paracetamol-only group. These findings suggest that quercetin exerts a protective effect against paracetamol-induced liver injury by reducing oxidative stress, inflammation, and apoptosis.