A study of the effect of Nigella sativa (black seeds) on methotrexate-induced hepatotoxicity in rabbits

Background: To evaluate the effectiveness of Nigella sativa (NS) in the prevention of hepatotoxicity of large doses of methotrexate (MTX) (IP) in rabbits.Methods: Three groups of male rabbits, six in each were used. Oral dosing was administered as a paste; formula 1 was prepared by mixing 2 g flour with water; formula 2 contained flour and NS and water. Group 1 was fed with formula 1 daily and injected with 2 ml/kg normal saline IP. Group 2 was given formula 1 daily with 20 mg/kg MTX IP. Group 3 was fed with formula 2 daily + MTX 20 mg/kg IP. Injections were given weekly for 5 weeks, and then the animals were sacrificed at day 39. Liver enzymes, malondialdehyde (MDA), glutathione (GSH), and histopathology of the liver were evaluated.Results: Liver enzymes, serum, and liver MDA were significantly increased by MTX. MTX + NS treatment significantly reduced the rise in liver enzymes, MDA in serum with little effect on liver MDA. Serum aspartate aminotransferase, alkaline phosphatase, and bilirubin were reduced from 82.8±18.04 U/L, 4.9±2.0 kind and king unit/100 ml and 0.74±0.1 mg/dl to 56.1±7.5, 2.0±0.6 and 0.27±0.1 respectively. Unexpectedly, serum and liver GSH were slightly increased by MTX. Treatment with MTX + NS further increased these levels. Histologically, portal and lobular sinusoidal dilatation, lymphocytic infiltration, and hepatocyte hydropic degeneration were seen in all rabbits on MTX, which disappeared in three rabbits on NS + MTX.Conclusion: NS is hepatoprotective against MTX induced hepatotoxicity