H1 antihistamines are the most widely used drugs for relieving symptoms of histamine-mediated disease. Although chlorpheniramine
maleate and cetirizine hydrochloride have tolerable side effects, they induce severe side effects on chronic use such as
hepatitis and cholestatic jaundice. Oxidative stress has been implicated as a mechanism of drug-induced hepatotoxicity. LCarnitine
is an effective biological active compound that is involved in oxidation of fatty acids in the liver through transportation
of fatty acids into the mitochondria for energy production from fat. L-Carnitine has well-known antioxidant properties, improves
hepatic function, and improves mitochondrial function in hepatic cells. In the present study, we evaluated the possible role of
oxidative stress and the therapeutic and hepatoprotective effect of L-carnitine on chlorpheniramine maleate– and cetirizine
hydrochloride–induced liver damage during chronic use. Methods are measurement of ALT, AST, ALP and albumin serum
levels and measurement of hepatic oxidative stress biomarkers MDA and GSH in groups with and without combination with Lcarnitine.
Histopathological examination of changes in hepatic tissue and scoring of the induced hepatic damage was conducted
in all treatment groups. Co-treatment of L-carnitine with chlorpheniramine maleate and cetirizine hydrochloride significantly
improved the deteriorated hepatic function as indicated by reduction in the serum levels of ALT, AST, ALP, and elevation in
serum albumin levels compared with control and untreated groups. Moreover, co-administration of L-carnitine with chlorpheniramine
maleate and cetirizine hydrochloride decreased hepatic MDA and elevated hepatic GSH levels compared with control
and untreated groups. Ultrastructure examination of hepatic tissue found that co-treatment with L-carnitine decreased hepatic
necrosis and damage. In conclusion, oxidative stress can be a possible explanation of hepatic damage induced by chronic therapy
with chlorpheniramine maleate and cetirizine hydrochloride. L-Carnitine has prominent hepatoprotective effects on chlorpheniramine
maleate– and cetirizine hydrochloride–induced hepatic damage possibly through improvement of hepatic function and
decreasing oxidative stress.