Membrane-translocated SO₂/₃-PRDX3 disrupts cystine uptake and GPX4 activity: A pivotal mechanism of boron-induced renal ferroptosis in broiler

Boron (B), a widely utilized non-metallic element in industrial, agricultural, and medical applications, has garnered significant attention due to its documented reproductive and developmental toxicity. Although the kidney plays a pivotal role in boron metabolism and excretion, the precise mechanisms underlying its nephrotoxicity remain incompletely elucidated. This study systematically investigated the toxic effects of boron exposure on chicken kidneys and its underlying molecular mechanisms, employing both in vivo chicken kidney tissues and an in vitro model of primary chicken renal tubular epithelial cells. Our findings demonstrate that boron exposure significantly impaired growth performance and renal function in broilers, induced histopathological alterations in kidney tissues, disrupted renal iron metabolism homeostasis, and triggered ferroptosis. Mechanistic exploration revealed that during boron-induced ferroptosis, peroxiredoxin 3 (PRDX3) underwent hyperoxidation (forming SO 2/3 -PRDX3) and aberrantly translocated to the cell membrane. Intriguingly, the membrane localization of SO 2/3 -PRDX3 impaired cellular cystine uptake, consequently inhibiting the synthesis of the critical antioxidant tripeptide glutathione (GSH), thereby exacerbating the ferroptosis process. Furthermore, dysfunctional SO 2/3 -PRDX3 could affect the core antioxidant activity of glutathione peroxidase 4 (GPX4), weakening cellular defenses against lipid peroxidation. In conclusion, boron exposure induces renal damage in chickens by activating the ferroptosis pathway. This activation is mediated through PRDX3 hyperoxidation, its subsequent membrane translocation, and the resulting impairment of cysteine uptake and GSH biosynthesis. SO 2/3 -PRDX3 dysfunction represents a critical molecular event in boron-induced nephrotoxicity in broiler chickens. • Boron exposure leads to accumulation within the kidney tissue. • The accumulation of boron in the renal tissue may have detrimental effects on kidney function. • The underlying mechanisms of boron-induced kidney injury involve iron metabolism disorders and ferroptosis. • Boron exposure induces superoxidation of PRDX3 in CEKs. • SO 2/3 -PRDX3 inhibits cystine uptake and exacerbates ferroptosis.