The present study aims to evaluate the effects of methotrexate (MTX) with and without vitamin A (Vit. A) on some biochemical parameters and histological structure in male rabbits liver. Twenty male rabbits weighing 1250-1480 gm were divided into four equal number groups. The first group was given 2 ml distilled water as control group. The second group was given MTX (20 mg/kg), the third group was given Vit. A (5000 IU), while the fourth group was given MTX (20 mg/kg) +Vit. A (5000 IU) in alternative days. Following four weeks of treatment, lipid profile total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), [low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL)]; in addition to thyroid hormones triiodothyronine (T3) and thyroxin (T4)] and liver enzymes [glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT)] were determined in the serum. Also, the histological examination of liver of all the experimental groups were carried out. The results were revealed that the treatment with MTX caused a significant P≤0.05 increases in TC, HDL, LDL, T4, and GPT when compared with the control group. The treatment with Vit. A did not cause any significant P≥0.05 differences in all the studied parameters. The MTX+Vit. A treated group showed a significant P≤0.05 increases only in GPT compared with the control group; while a significant P≤0.05 decreases was found in TC, HDL, T3, T4, and GOT when compared with the MTX treated group. The histological examination of the liver sections showed that MTX administration caused major histological changes in comparison with the control such as inflammatory cell infiltrations, vascular congestion, sinusoidal dilatation and granular degeneration of hepatocytes. Treatment with Vit. A showed a typical structure in liver tissue. While in MTX+Vit. A group, the histological changes were less severe than those in the MTX treated group; these changes were granular degeneration of hepatocytes and sinusoidal dilatation at low levels. The overall results of this study confirmed that administration of Vit. A decreased the side effects of MTX; this protective effect of Vit. A may have clinical applications in chemotherapy.

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