PROTECTIVE ROLE OF SILYMARIN AND ITS SYNERGISTIC COMBINATIONS IN PARACETAMOL-INDUCED HEPATOTOXICITY

Abstract

Paracetamol overdose is a common cause of drug-induced hepatotoxicity, primarily due to oxidative stress and depletion of hepatic glutathione reserves. Silymarin, a well-known hepatoprotective flavonoid, exerts antioxidant, anti-inflammatory, and membrane-stabilizing effects, while omega-3 fatty acids and coenzyme Q10 are established as potent modulators of oxidative stress and mitochondrial function. The present study aimed to evaluate the hepatoprotective effect of silymarin alone and its combination with omega-3 fatty acids and coenzyme Q10 against paracetamol-induced hepatotoxicity in rats. Experimental animals were divided into control, toxic, and treatment groups receiving silymarin alone or in combination with omega-3 fatty acids and/or coenzyme Q10. Hepatoprotection was assessed using biochemical parameters such as serum ALT, AST, ALP, bilirubin, and total protein, along with antioxidant markers including MDA, SOD, and catalase. Histopathological examination of liver tissue was also performed. Results demonstrated that silymarin alone significantly reduced biochemical markers of liver injury and improved antioxidant status compared to the toxic control. However, the combination of silymarin with omega-3 fatty acids and coenzyme Q10 produced superior hepatoprotective effects, with marked reductions in oxidative stress, normalization of liver function tests, and improved histological architecture. The findings suggest that the synergistic use of natural antioxidants may provide enhanced protection against paracetamol-induced hepatotoxicity compared to monotherapy.