The Protective Effects of Echinops Heterophyllus Aqueous Extract Against Methotrexate-Induced Hepatotoxicity in Rabbits

Abstract

Objective: The aim of this study was to investigate antioxidant and hepatoprotective properties of Iraqi Echinops heterophyllus aqueous crude extract and its flavonoid fraction against methotrexate (MTX)-induced hepatotoxicity in rabbits.Methods: MTX-induced hepatotoxicity by administration of 20 mg/kg MTX intraperitoneally for 3 successive days was used as animal model, and animals were arrayed in four groups with eight animals in each group: Group 1 was the healthy control, Group 2 - the negative control receiving MTX only, Group 3 received MTX+crude extract of E. heterophyllus, and Group 4 administered MTX+flavonoid fraction of E. heterophyllus. The study duration was 10 days; at day 11, animals were sacrificed, and the blood samples were obtained for the measurement of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, total protein, and albumin as well as ELISA assay of the oxidative stress markers such as glutathione (GSH) and malondialdehyde (MDA). The liver was dissected and processed for histopathological investigation and scoring. Statistical analysis was performed to investigate the significance of each result.Results: The study results revealed severe liver damage due to MTX administration in the negative control (induced-non treated) group in comparison with healthy group, also there was significant hepatoprotective effect after administration of the crude extract of E. heterophyllus, and flavonoid fraction from E. heterophyllus shown after biochemical liver function tests and anti-oxidant properties demonstrated by the measurement of oxidative stress markers MDA and GSH. The crude extract of E. heterophyllus shown superior hepatoprotective and antioxidant effect. Histopathological scoring showed a remarkable decrease in the scores of the treatment groups in comparison with the high score in the MTX only treated group.Conclusions: MTX administered in a dose of 20 mg/kg for 3 successive days causes marked liver injury, while treatment with the crude extract and flavonoid fraction of E. heterophyllus significantly ameliorates MTX-induced liver damage, although the crude extract of E. heterophyllus seems to have the most hepatoprotective properties.

The Genus Echinops: Phytochemistry and Biological Activities: A Review

“…Davis was established in rabbits. The crude ethanolic extract (250 mg/kg) significantly decreased the serum proteins, liver enzymes, and oxidative stress markers than the flavonoid fraction (Abdulmohsin et al, 2019).…”

Antioxidant and Hepatoprotective Potential of Echinops ritro L. Extracts on Induced Oxidative Stress In Vitro/In Vivo

“…Methotrexate-induced hepatotoxicity was also used to evaluate the hepatoprotective effect of E. heterophyllus extract from aerial parts and flavonoid fraction in rabbits. The ethanolic extract at a dose of 250 mg/kg significantly decreased the serum proteins, liver enzymes, and oxidative stress markers compared to the flavonoid fraction [ 14 ]. The methanol root extract of E. giganteus showed in vitro a free radical scavenging effect with 12.54 mg Trolox equivalent per 100 g [ 15 ].…”