摘要
Aflatoxin B1 (AFB1) and ochratoxin A (OTA) are well-known to promote hepatotoxicity and nephrotoxicity in vivo, which may be counteracted by natural compounds like fermented whey (FW). Carbamoyl phosphate synthetase 1 (CPS1) and kidney injury molecule 1 (KIM-1) are typical biomarkers used to detect liver and kidney damage, respectively. Thus, RT-qPCR and droplet digital PCR (ddPCR) analysis were performed to assess the potential beneficial effect of FW against AFB1 and OTA hepatotoxicity and nephrotoxicity in male and female Wistar rats by analyzing the altered gene expression of hepatic CPS1 and renal KIM-1 after 28 days of oral exposure. In male livers, the most damaging treatment was AFB1 by reducing CPS1 expression, which was totally reversed by FW-administration. This bioactive compound also improved gene expression changes induced by OTA and mycotoxins mixture. In female livers, a significant CPS1 overexpression was observed for each exposure performed, in which FW-supplementation reported no remarkable differences compared with mycotoxins exposure. Conversely, in the kidneys of male and female rats, exposure to mycotoxins promoted renal damage by altering KIM-1 gene expression, being OTA-exposure the most harmful condition. In both sexes, ddPCR analysis demonstrated that FW-addition modulated mycotoxins induced KIM-1 gene expression changes, thus reducing kidney damage. In this organ, sex-related responses were not clearly observed. Therefore, these findings confirmed that AFB1 and OTA-promoted hepatotoxicity and nephrotoxicity in vivo, which could be modulated by dietary FW supplementation.
摘要译文
黄曲霉毒素B1（AFB1）和Ochratoxin A（OTA）众所周知，可以在体内促进肝毒性和肾毒性，这可能会被诸如发酵乳清（FW）等天然化合物所抵消。磷酸磷酸合成酶1（CPS1）和肾损伤分子1（KIM-1）分别用于检测肝脏和肾脏损伤。因此，进行了RT-QPCR和液滴数字PCR（DDPCR）分析，以评估FW对AFB1和OTA肝毒性和雌性Wistar大鼠的潜在有益作用，并通过分析肝CPS1和肾脏KIM-1的基因表达改变的基因表达和肾脏KIM-1，以及肾脏KIM-1的改变。口腔暴露28天后。在雄性肝脏中，最具破坏性的治疗方法是通过降低CPS1表达，这完全被FW-Administration逆转。这种生物活性化合物还改善了由OTA和霉菌毒素混合物诱导的基因表达变化。在雌性肝脏中，每次暴露都观察到CPS1明显的过表达，其中FW支持与霉菌毒素暴露相比没有明显的差异。相反，在雄性和雌性大鼠的肾脏中，暴露于霉菌毒素通过改变KIM-1基因表达来促进肾脏损伤，这是OTA暴露是最有害的。在这两个性别中，DDPCR分析表明，FW-ADDITION调节霉菌毒素诱导KIM-1基因表达变化，从而减少肾脏损伤。在此器官中，没有明确观察到与性别相关的反应。因此，这些发现证实了AFB1和OTA促进的肝毒性和体内肾毒性，可以通过补充饮食FW来调节。
Massimo Frangiamone; Alexander Yemelin; Alessandra Cimbalo; Guillermina Font; Eckhard Thines ;amp; Lara Manyes. Fermented whey modulated AFB1 and OTA-induced hepatotoxicity and nephrotoxicity in vivo. A relative and absolute quantification about sex differences[J]. Toxicology Mechanisms & Methods, 2023,33(6): 529-540