Metformin ameliorates methotrexate-induced hepatotoxicity

Najah R Hadi, Fadhil G Al-Amran, Asma Swadi, Najah R Hadi, Fadhil G Al-Amran, Asma Swadi

Abstract

Objective: To study the effect of metformin on amelioration of hepatotoxicity induced by methotrexate.

Materials and methods: After a 2-weeks of acclimatization period, the animals were randomly separated into three groups (seven rabbits each), all groups were maintained on standard chow diet throughout the experiment (8 weeks). Group 1 was treated with normal saline water (control), Group 2 with methotrexate (MTX, hepatotoxic), and Group 3 with MTX plus metformin. Induction of hepatotoxicity was carried out by administration of MTX to the rabbit in a dose of 0.25 mg/kg /day i.m. for 8 weeks.

Results: The treatment with MTX to rabbits for 8 weeks resulted in significant changes in serum liver enzymes, as compared to the baseline group. SGOT, SGPT, ALP, and bilirubin were significantly increased (P < 0.001), while total serum protein was significantly decreased. Similarly, 8 weeks of MTX treatment produced significant (P < 0.001) prolongation in PT. PTT was not significantly changed. It was found that serum MDA levels and SOD activity were significantly increased (P < 0.001), while serum GSH levels were significantly decreased (P < 0.001). Adding metformin to MTX is found to be significantly (P < 0.001) reduced the liver function test and shortening of PT and a significant increase in TSP (P < 0.001).

Conclusion: It can be concluded that administration of metformin restored the altered liver function parameters and produced significant improvement in liver histopathological findings. Therefore, this additive drug possesses hepatoprotection against MTX-induced hepatotoxicity.

Keywords: Hepatotoxicity; metformin; methotrexate.

Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1
Figure 1
Photomicrograph of the liver section of normal rabbits (no abnormality) shows the normal architecture. Stained with hematoxylin and eosin (× 40)
Figure 2
Figure 2
Photomicrograph of histological liver sections of rabbits (severe changes shows large area of necrosis) treated with MTX alone. Stained with hematoxylin and eosin (×10)
Figure 3
Figure 3
Photomicrograph of the liver section with moderate histological findings (portal tract dilatation and congestion inflammatory cell infiltration, sinusoidal dilatation congestion). Stained with hematoxylin and eosin (×40)
Figure 4
Figure 4
Photomicrograph of histological liver sections of rabbits (severe changes shows large area of necrosis) treated with MTX alone. Stained with hematoxylin and eosin (×10)

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