Ferroptosis in veterinary medicine: mechanisms, therapies, and unmet challenges.

Abstract

Ferroptosis, a regulated cell death, has emerged as a critical contributor to various pathological conditions in animals, particularly infectious, reproductive, musculoskeletal, and nutritional diseases. Ferroptosis differs from apoptosis, necrosis, and other types of cell death, being characterized by the production of reactive oxygen species and excessive lipid peroxidation. Research indicates a close interplay between oxidative stress and ferroptosis in veterinary contexts, where pathogens may manipulate ferroptosis to alter host immune responses, underlining its role in disease progression and defence mechanisms. Key regulators such as SLC7A11, ACSL4, and FSP1 have also been implicated in ferroptosis-related pathophysiology across animal species. Nutritional deficiencies, such as selenium deficiency, impair the activity of GPX4, a key antioxidant enzyme that suppresses ferroptotic pathways. Several therapeutic strategies, such as antioxidants, ferroptosis inhibitors, nutritional supplements, and iron chelators, are currently being explored in veterinary medicine, requiring tailored approaches due to metabolic differences among species. Despite increasing attention in human medicine, ferroptosis remains poorly understood in animal health. Therefore, this review consolidates current knowledge on ferroptosis in veterinary medicine and explores its mechanistic contribution to the pathogenesis of animal diseases. We highlight the emerging strategies for therapeutic intervention and improved animal health outcomes.