Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death

Year 2023, Volume: 24 Issue: 2, 148 - 154, 30.06.2023

Cevat Gençer , Alpaslan Gökçimen , Erhan Bayraktar , Fatih Birtekocak , Kadri Murat Gürses

Abstract

Objective: The liver is one of the most important internal organs in the human body and has high regenerative properties. It performs the functions of protein synthesis, intake, storage, and distribution of nutrients and vitamins from the blood. In this study, we investigated the curative effect of metformin (Met) on doxorubicin (DOX)-induced liver damage.
Materials and Methods: A total of 32 Wistar-albino rats were divided into four groups: control, Met, DOX, and DOX + Met groups. The DOX and DOX + Met groups received four doses of DOX. Met was gavaged daily for 15 days in the DOX + Met and Met groups. Structural liver injury was evaluated with hematoxylin-eosin, picro-sirius, TUNEL, and nuclear factor kB (NF-kB) antibody staining. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total antioxidative status (TAS), total oxidative status (TOS), and hydroxyproline levels were measured as biochemical parameters.
Results: The DOX group was found to have a significant structural liver injury characterized by hyperchromatic nuclei in hepatocytes, widespread sinusoidal dilatations, and granular and vacuolar degeneration. Increased NF-kB staining and the apoptotic index were also detected in the DOX group. Biochemical tests revealed an increase in ALT, AST, and TOS levels and a decrease in TAS levels in the DOX group. Met administration provided a significant improvement in the structural changes caused by DOX. In addition, the DOX + Met group had lower NF-kB staining, apoptotic index, ALT, and TOS levels and a higher TAS level compared to the DOX group.
Conclusion: Our findings indicate that Met alleviates DOX-induced structural liver injury by reducing oxidative stress, inflammation, and excessive cell death.

Keywords

Doxorubicin , metformin , liver injury , apoptosis , oxidative stress

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