Evaluation of the Protective Efficacy of Folic Acid Against D-Galactosamine-Induced Hepatotoxicity: A Comprehensive Analysis of Biochemical, Oxidative, and Immunological Responses in a Rat Model.

Background: D-galactosamine (D-GalN) is a well-studied hepatotoxin used in research to model liver injury, causing oxidative stress and inflammation. Folic acid (vitamin B9), with its antioxidant and immunomodulatory effects, may protect against such hepatic damage. This study aimed to evaluate the potential protective effects of folic acid against D-GalN-induced liver injury in rats. Methods: Thirty-six male albino rats were divided into six groups (n = 6 each). Group I (control) received saline; Group II received daily folic acid (20 mg/kg) for a month. Groups III and IV received a single dose of D-GalN (300 mg/kg) on Days 1 and 30, respectively. Groups V and VI were treated with daily folic acid followed by D-GalN on Days 1 and 30, respectively. We assessed serum liver enzymes, kidney function markers, lipid profile, oxidative stress markers, cytokines, immunoglobulins, and histopathological changes. Results: Serum levels of ALT, AST, ALP, GGT, bilirubin, urea, creatinine, TNF-α, IL-1β, IFN-γ, liver MDA, TC, TG, and LDL were markedly increased in the D-GalN group compared to the control group. Conversely, serum total protein, albumin, IgG, IgM, Liver GSH, and HDL levels were reduced. Pretreatment with folic acid significantly mitigated all these adverse effects. Conclusion: Folic acid protects against D-GalN-induced liver toxicity by enhancing liver and kidney function, restoring lipid metabolism, reducing oxidative stress, and modulating immune responses, highlighting its therapeutic potential for managing liver injury and related immunoinflammatory disturbances.