Abstract
Introduction: Valproic acid (VPA) is a widely prescribed antiepileptic drug, which might induce serious hepatic disorders . Silymarin is currently used as a supportive therapy of liver disorders. Aim of the study: In this study we evaluated the protective effects of silymarin on valproic acid induced hepatotoxicity . Material and Methods: seventy adult male albino rats were divided into 7 groups (10 each), (Ia) negative control, (Ib) positive control, (II) silymarin group, received17.5 mg/kg. (IIIa) low dose VAP group, received 200mg/kg , (IIIb) high dose VAP group received 400 mg/kg (IVa) low dose VPA + silymarin group and (IVb) high dose VPA + silymarin group received doses as previously mentioned. The drugs were gavaged once daily, 6 days/week for 8 weeks, at the end of the experiment rats were sacrificed and estimation of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in the blood, malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in liver tissues and histopathological and immunnohistochemical examination of liver tissues were carried out. Results: this study showed significant increase in serum ALT, ALP and hepatic MDA contents while GSH-Px activity significantly reduced (especially in high dose VPA group) when compared with the control. Histopathological changes showed patchy microvesicular steatosis, focal necrosis of hepatocytes, dilated congested central vein and sinusoids. Immunolocalization of Bcl-2 revealed dose dependent weak cytoplasmic staining in the hepatocytes surrounding the central vein. VPA+ Silymarin groups showed partial improvement. Conclusion: It concluded that VPA has dose dependent toxic effects on liver that might be ameliorated by concomitant use of silymarin.
Highlights
Valproic acid (VPA) is a widely prescribed antiepileptic drug, which might induce serious hepatic disorders
At the end of the experiment rats were anaesthetized by ether and blood samples were collected from the retro-orbital plexus for estimation of liver functions (ALT and alkaline phosphatase (ALP)), rats were sacrificed by decapitation and abdominal incision was done and the liver extracted for measurement of hepatic MDA content and GSH-Px activity as follows: Assessment of liver function tests (LFTs)
Valproic acid caused significant increase in the mean values of ALT, ALP and hepatic MDA contents (P < 0.05) while GSH-Px activity significantly reduced (P < 0.05) in group IIIa and IIIb when compared with control group
Summary
Valproic acid (VPA) is a widely prescribed antiepileptic drug, which might induce serious hepatic disorders. Silymarin is currently used as a supportive therapy of liver disorders. Aim of the study: In this study we evaluated the protective effects of silymarin on valproic acid induced hepatotoxicity. Conclusion: It concluded that VPA has dose dependent toxic effects on liver that might be ameliorated by concomitant use of silymarin. Silymarin is widely used as a hepatoprotectant and as a supportive therapy for liver disorders such as cirrhosis, hepatitis and fatty acid infiltration due to alcohol and toxic chemicals (Ball and Kowdley, 2005; Kren and Walterova, 2005)
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