Dose-dependent hepatoprotective effects of ochnaflavone against paraquat-induced hepatic damage in albino rats

Paraquat (PQ) is a quaternary ammonium compound extremely toxic to humans and animals, causing multi-organ toxicity, particularly hepatic damage.Ochnaflavone (OCH), a biflavonoid isolated from Ochna integerrima, possesses potent anti-cancer, anti-inflammatory, anti-diabetic and antioxidative properties.This investigation was intended to estimate the dose-dependent remedial efficacy of OCH to combat PQ-mediated liver toxicity in male albino rats.The experimental period lasted for 8 weeks.96 adult male rats (Rattus norvegicus; albino strain) were randomly allocated into 8 experimental groups: Control, PQ-intoxicated (5mg/kg), PQ+OCH1 (5mg/kg+25mg/kg), PQ+OCH2 (5mg/kg+50mg/kg), PQ+OCH3 (5mg/kg+100mg/kg), OCH1 (25mg/kg), OCH2 (50mg/kg), and OCH3 (100mg/kg).OCH was administered concurrently with PQ in the co-treated groups.Following oral administration, biochemical and liver function markers were determined along with histopathological observation.Results revealed that PQ intoxication downregulated the antioxidant enzymes activities such as glutathione reductase (GSR), heme oxygenase-1 (HO-1), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione (GSH) content, while concurrently upregulated the malondialdehyde (MDA) level and reactive oxygen species (ROS) concentration.Furthermore, PQ administration significantly provoked the concentrations of serum hepatic enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), concurrently elevating the concentrations of inflammatory indices: tumor necrosis factor-α (TNF-α), cyclooxygenase 2 (COX-2), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6) as well as interleukin-1β (IL-1β).Additionally, PQ-treatment instigated histopathological abnormalities in liver tissues.However, OCH co-treatment significantly mitigated these biochemical and histopathological changes instigated by PQ exposure.Therefore, OCH attenuates PQ-induced hepatotoxicity in a dose-dependent manner through its potent antioxidative and anti-inflammatory potential.