Naringenin: a potential natural remedy against methotrexate-induced hepatotoxicity in rats

Abstract

Hepatotoxicity is an adverse side effect of methotrexate (MTX) administration for the treatment of different malignancies, psoriasis, and rheumatoid arthritis (RA). Naringenin (NAR) is a citrus flavone with multiple pharmacological characteristics. In this study, we aimed to investigate the protective effects of NAR on MTX-induced hepatotoxicity in rats. For this purpose, 32 Wistar rats were randomly divided into four experimental groups as group 1 Control, group 2 NAR (50 mg/kg/d, o.p.), group 3 MTX (20 mg/kg/d, i.p.), group 4 NAR + MTX. NAR was administrated for 10 consecutive days and MTX was injected on the ninth day. The results indicated that MTX significantly increased malondialdehyde (MDA), NO, TNF-α, and IL-6 levels in the liver. On the other hand, administration of MTX reduced the GSH content, as well as CAT, SOD, and GPx levels. NAR administration remarkably improved MTX-induced alteration of biochemical biomarkers. Our findings were confirmed by the histopathological examination of the liver. Based on our findings, NAR may inhibit MTX-induced hepatotoxicity through scavenging reactive free radicals and inducing anti-inflammatory effects.

Keywords:

• Methotrexate
• naringenin
• hepatotoxicity
• oxidative stress
• inflammatory
• rat

Acknowledgments

This study was extracted from a Pharm D thesis in pharmaceutical sciences by Reza Badparva.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This study was supported by the Deputy of Research Affairs of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran (grant number: MPRC-9621).