Bovine Lactoferrin Mitigates Oxidative Stress and Inflammation in CCL4 and High-fat Diet-induced NAFLD in C57BL/6 Mice

Background: Impacting approximately 20-30% of adults, nonalcoholic fatty liver disease (NAFLD) is the leading contributor to liver dysfunction. This condition is characterized by the accumulation of more than 5% fat in the liver without the presence of concurrent chronic liver diseases or alcohol abuse. NAFLD manifests across a spectrum ranging from simple steatosis to more complex forms involving hepatic lesions, inflammation and fibrosis. This research aimed to assess the therapeutic effectiveness of Bovine Lactoferrin (BLF) in a model of NAFLD using male C57BL/6 mice. Methods: Adult male C57BL6 mice, with an average weight of 28 g, were obtained and maintained in a consistent environment at 22±2oC for 6 weeks, following a regulated 12-hour light-12-hour dark cycle. Control groups 1 and 3 were provided with a standard pellet feed, while model groups 2, 4, 5 and 6 were supplied with a high-fat diet. Induction of NAFLD included administering a high-fat diet (HFD) and CCl4 (0.5 mg/kg with olive oil) twice a week via intraperitoneal injection over 6 weeks. After the experimental procedures, an assessment of serum-biochemical parameters, inflammatory cytokines, anti-oxidant profile and liver histopathology were conducted. Result: The results revealed significant (p less than 0.05) alteration in sero-biochemical parameters, inflammatory cytokines (IL-10, TNF-α, NF-kB and TGF-β) anti-oxidant profile (nitric oxide assay, TBARS, SOD, GSH and Catalase) and histopathology of group 2 as compared to other groups. The groups 4, 5 and 6 showed significant improvement in all the parameters compared to disease control. The findings from this study suggest that BLF could potentially function as a therapeutic intervention for mitigating hepatic injury, inflammation and fibrosis in NAFLD by deactivating NF-kB pathway.