Hepatoprotective Role of Stevia rebaudiana Against Methotrexate-Induced Liver Toxicity in Rats

Methotrexate (MTX) is the first drug of choice to treat numerous diseases. However, there is hepatotoxicity associated with its administration. Stevia rebaudiana is a potentially effective medication and a natural hypocaloric bio-sweeteners herb. Its leaves contain bioactive substances like vitamins, polyphenols, as well as steviol glycosides, making it suitable for both pharmaceutical applications and food. Adult male rats were divided into four groups: control, methotrexate (20 mg/kg b.wt., intraperitoneally on days 1 and 5), S. rebaudiana (300 mg/kg b.wt. orally), and MTX + S. rebaudiana. The MTX group rats increased in the liver enzyme activities (AST, ALT, GGT, and ALP), total bilirubin, α-fetoprotein, nitric oxide, and malondialdehyde. Meanwhile, it reduced the total protein, albumin content, antioxidant enzyme activities (POD, SOD, CAT, and GSH), and DNA fragmentation as compared to the control group. The administration of S. rebaudiana leaf extract orally at 300 mg/kg b.wt. to the MTX rat group caused a significant reduction in liver enzyme activities, total bilirubin, α-fetoprotein, MDA, and NO. Furthermore, they increased the albumin content, total protein, and antioxidant enzymes. Furthermore, histopathological examinations revealed that MTX causes major deleterious alterations in the structure of liver tissue, whereas S. rebaudiana treatment preserves the liver cellular structure without the appearance of any alterations. The current study demonstrated the hepatoprotective action of S. rebaudiana aqueous leaf extract as a natural therapeutic medication against MTX-induced hepatotoxicity because of its low cost, safe nature, and significant nutritional benefits.