The protective role of l-carnitine against 1st- and 2nd-generation antihistamine-induced liver injury in mice

  • Rania A. Abdel-EmamEmail author
  • Esraa A. Ahmed
  • Marwa F. Ali
Original Article


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. l-Carnitine 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 l-carnitine. 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.


Antihistamine Chlorpheniramine maleate Cetirizine hydrochloride Liver Hepatotoxicity Oxidative stress l-Carnitine 



The authors acknowledge the animal house of Assuit University for providing the experimental animals and every kind hand which helped and participated in the accomplishment of this work is deeply acknowledged.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.


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© Springer-Verlag London Ltd., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacology, Faculty of MedicineAssiut UniversityAssiutEgypt
  2. 2.Department of Pathology and Clinical Pathology, Faculty of Veterinary MedicineAssiut UniversityAssiutEgypt

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