Histidine, carnosine, and ergothioneine attenuate pyrazole/LPS-induced hepatotoxicity through modulation of CYP2E1, Nrf2, and NF-κB signaling in mice.

Authors

İlknur Genç, Fatma Hande Karpuzoğlu, İlayda Sözmen, Serhat Kılınç, Abdurrahman Fatih Aydın, Sidar Bağbudar, Semen Önder, Aydın Kerem Arslan, Semra Doğru Abbasoğlu, Müjdat Uysal

Published in

Molecular biology reports. Volume 53. Issue 1. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

Cytochrome P450 2E1 (CYP2E1) is key in liver damage from oxidative stress. The pyrazole (Pyr)- and lipopolysaccharide (LPS)- induced mouse model, which combines CYP2E1 induction with endotoxemia, is useful for studying liver protection. This study assessed how imidazole compounds (histidine, carnosine, and ergothioneine) affect Pyr + LPS-induced liver injury and the mechanisms involved.
Male C57BL/6J mice received histidine (250 mg/kg, i.p.), carnosine (250 mg/kg, i.p.), histidine + carnosine (250 mg/kg each, i.p.), or ergothioneine (70 mg/kg, oral) for 10 consecutive days. Pyrazole (150 mg/kg, i.p.) was administered on days 8 and 9, followed by LPS (10 mg/kg, i.p.) on day 10. Serum ALT and AST activities, hepatic oxidative stress markers (ROS, TBARS, AOPP), antioxidant parameters (GSH, SOD, GSH-Px, FRAP), CYP2E1 protein levels, nitric oxide metabolites (NOx), and mRNA expressions of Nrf2, HO-1, NF-κB, TNF-α, and IL-6 were determined. Histopathological examination was also performed.
Pyr + LPS administration significantly elevated serum ALT and AST levels, hepatic CYP2E1, oxidative stress markers, and NOx, while reducing antioxidant defenses. NF-κB, TNF-α, IL-6, and HO-1 mRNA expressions were elevated. Pre-treatment with all imidazole compounds significantly attenuated these alterations, reduced CYP2E1 levels, and further upregulated HO-1 expression. The combination of histidine and carnosine also increased Nrf2 mRNA expression. Histopathological findings corroborated the biochemical results.
Histidine, carnosine, and ergothioneine protected against Pyr + LPS-induced hepatic injury and reduced oxidative stress. These effects were accompanied by alterations in CYP2E1 protein levels and NF-κB/Nrf2/HO-1-related gene expression; however, further studies are needed to clarify the underlying mechanisms.

PMID:
42455220
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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