Aim: The study aimed at studying the hepatoprotective effect of L-carnitine against lead (Pb) acetate-induced
hepatocellular injury, emphasizing the role of caspase-3 and glycogen synthase kinase-3β in hepatocellular
apoptosis and inflammation.
Materials and methods: Male Wistar rats were used. The experimental approach involved estimation of the liver
enzymes' serum levels. Oxidative and inflammatory biomarkers were measured in hepatic tissue homogenates.
Paraffin-embedded hepatic sections were prepared for histopathology and immunohistochemistry. Quantitative
determination of the phosphorylated glycogen synthase kinase-3 beta was performed.
Key findings: The serum showed a significant elevation in ALT, AST, and LDH; tissue homogenates showed significant
elevation in lipid peroxide and inflammatory biomarkers with significant reduction in reduced glutathione
in the Pb acetate-treated group. Co-administration of L-carnitine with Pb acetate produced significant
reduction in liver enzymes with significant improvement in oxidant, antioxidant and inflammatory markers.
Lead acetate treatment significantly reduced the phosphorylated glycogen synthase kinase-3 beta, while Lcarnitine
enhanced its phosphorylation. Histopathological examination showed inflammatory reaction around
blood vessels with fatty degeneration in hepatocytes of the Pb acetate intoxicated group. L-Carnitine caused a
decrease in hepatic damage with minimal vascular alterations in central vein. Caspase-3 expression in hepatocytes
was decreased in Pb-treated group supplemented with L-carnitine.
Significance: Our study reveals that oxidative stress and inflammation participate in Pb acetate-induced hepatocellular
injury. Glycogen synthase kinase-3β and caspase-3 play role in Pb acetate-induced hepatic damage. LCarnitine
shows significant protective effects against hepatocellular apoptosis and inflammation induced by Pb
acetate through antioxidant, anti-inflammatory and anti-apoptotic pathways in part mediated by GSK-3β
inhibition.