Abstract

ANTIOXIDANT AND ANTI-INFLAMMATORY EFFECTS OF ORIDONIN ON DEXAMETHASONE-INDUCED HEPATOTOXICITY IN RATS

Mutni Kh. Alreshidi, Kareem Saad, Marwa S. Zaghloul*, Manar A. Nader

ABSTRACT

Background: Glucocorticoids are widely used for their anti-inflammatory and immunosuppressive effects but are associated with oxidative stress- and inflammation-driven hepatic injury following prolonged administration. To date, oridonin (a bioactive diterpenoid isolated from Isodon rubescens) has been reported to resist oxidation and inflammation in multiple experimental models but its potential as a hepatoprotective agent remains incompletely documented against glucocorticoid-induced liver injury. Purpose: To investigate the role and mechanism of oridonin on dexamethasone-induced hepatic injury in rats. Methods: Eighteen male rats were randomly divided into 3 groups (n = 6): control, dexamethasone group (8 mg/kg i.p. once daily for the last six days of a 12-day protocol), and/oridonin-pretreated groups (20mg/kg orally once daily for 12 days) co-administeredwith dexamethasone. Serum ALT activity was used to evaluate hepatic injury. Hepatic GSH, CAT and TAC were used to assess oxidant/antioxidant balance. iNOS and IL6 were used to assess inflammatory status. Results: Dexamethasone administration markedly increased serum ALT, as well as inflammatory markers (iNOS and IL6), while decreasing CAT, GSH and TAC compared to control (p < 0.05). The alterations of the above markers were significantly improved by co-treatment with oridonin, which also shortened and reduced ALT levels to approximately normal. Conclusion: Oridonin protects the liver against dexamethasone-induced liver injury, which may mainly be via antioxidant and anti-inflammatory mechanisms, indicating its potential as an adjunct hepatoprotective agent.

Keywords: Oridonin; Dexamethasone; Hepatoprotection; Oxidative stress; Inflammation; ALT.