Antituberculosis drug-induced hepatotoxicity: Preclinical benefit of glutamine

Year 2024, Volume: 6 Issue: 3, 43 - 49, 31.12.2024

Elias Adikwu , Tobechı Brendan Nnanna , Koya Safia

https://doi.org/10.51262/ejtox.1554123

Abstract

Background: Rifampicin/isoniazid/pyrazinamide/ethambutol (RIPE) which is the corner stone for the treatment of tuberculosis may cause hepatotoxicity. Glutamine (Gtn) is an important amino acid with potential cell-regulative and cytoprotective capabilities. Objective: This study assessed the ability of Gtn to prevent RIPE-induced hepatotoxicity in rats. Materials and Methods: Thirty adult Wistar rats (both sexes) weighing 180-220 were used. The rats were randomized into 6 groups of n=5/group and orally administered with the experimental agents daily for 30 days as follows: Groups 1-3 were administered with ([Control] normal saline, 0.2mL), Gtn (80mg/kg) and RIPE (Rifampicin 150, isoniazid/75, pyrazinamide 400 and ethambutol 275 mg/kg), respectively. Groups 4-6 were supplemented with Gtn (20mg/kg, 40mg/kg, 80mg/kg) prior to the administration of RIPE, respectively. On day 31, the rats were weighed, anesthetized and blood samples were collected and assessed for serum biochemical markers. Liver samples were weighed and examined for histology and oxidative stress markers. Results: Body weight, liver superoxide dismutase, glutathione peroxidase, catalase and glutathione levels decreased significantly (p<0.001) whereas liver weight, serum lactate dehydrogenase, gamma glutamyl transferease, aminotransferases, alkaline phosphatase, total bilirubin and liver malondialdehyde levels increased significantly (p<0.001) in RIPE -administered rats when compared to control. RIPE caused hepatocelluar necrosis, and steatosis. However, the aforementioned changes caused by RIPE were restored in a dose-related fashion by Gtn supplementation at 20mg/kg (p<0.05), 40mg/kg (p<0.01) and 80 mg/kg (p<0.001) when compared to the RIPE. Also, Gtn) supplementation restored liver histology. Conclusion: Gtn prevents RIPE-induced hepatotoxicity. It may be clinically useful for RIPE related hepatotoxicity.

Keywords

Antituberculosis drug, liver, toxicity, glutamine, protection

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