Abstract:
Phytic acid (PA) is a natural antioxidant with various biological activities, providing protective effects in multiple animals. Ochratoxin A (OTA) is a mold toxin commonly found in feed, which induces multi-organ damage, with kidney being the target organ of its toxicity. This study investigates the protective effects of PA on OTA-induced renal damage and its potential mechanisms in chicks. The results demonstrates that PA treatment restores OTA-induced renal pathological injuries, reverses the diminished activities of antioxidant enzymes, reduces the accumulation of malondialdehyde, and normalizes the expression of pro-inflammatory cytokines, which confirms that PA can alleviate OTA-induced renal damage. Further investigations reveal that OTA-induced renal injury accompanied by an increase in tissue iron content and the transcription levels of ferroptosis-related genes (TFR, ACSL4, and HO-1), and a decrease in the levels of SLC7A11 and GPX4. PA treatment reverses all these effects, indicating that PA mitigates OTA-induced renal ferroptosis. Moreover, PA supplementation improves intestinal morphology and mucosal function, corrects OTA-induced changes in the intestinal microbiota. Besides, PA microbiota transplantation alleviates renal inflammation and oxidative stress caused by OTA. In conclusion, PA plays a protective role against renal damage through the regulation of ferroptosis and the intestinal microbiota, possibly providing novel insights into the control and prevention of OTA-related nephrotoxicity.
摘要:
植酸(PA)是一种具有多种生物活性的天然抗氧化剂。在多种动物中提供保护作用。曲霉毒素A(OTA)是一种常见的霉菌毒素,在饲料中,导致多器官损伤,肾脏是其毒性的靶器官。本研究探讨了PA对OTA诱导的雏鸡肾损伤的保护作用及其潜在机制。结果表明,PA治疗可以恢复OTA引起的肾脏病理损伤,逆转抗氧化酶活性的减少,减少丙二醛的积累,并使促炎细胞因子的表达正常化,这证实了PA可以减轻OTA诱导的肾损伤。进一步的研究表明,OTA诱导的肾损伤伴随着组织铁含量的增加和铁凋亡相关基因的转录水平(TFR,ACSL4和HO-1),SLC7A11和GPX4的水平下降。PA治疗逆转了所有这些影响,表明PA减轻了OTA诱导的肾铁性凋亡。此外,PA补充改善肠道形态和粘膜功能,纠正OTA诱导的肠道微生物群变化。此外,PA微生物移植减轻OTA引起的肾脏炎症和氧化应激。总之,PA通过调节铁细胞凋亡和肠道菌群对肾损伤具有保护作用,可能为OTA相关肾毒性的控制和预防提供新的见解。