醋酸铅（PbAc）是五种最危险的有毒重金属之一，尤其导致肾损伤，对人类和动物的健康构成严重风险。芥子酸（SNP）是水果和蔬菜中天然存在的黄酮类化合物，其具有抗氧化、抗炎和抗癌特性。本研究首次通过生化、分子和组织学方法研究了SNP对PbAc诱导的大鼠肾毒性的氧化应激、炎症、细胞凋亡、自噬和内质网（ER）应激的影响。将35只斯普拉格－道氏大鼠随机分为5组，每组7只：对照组、PbAc组、SNP组（10mg/kg）、PbAc + SNP 5组、PbAC + SNP 10组。PbAc以每kg体重30mg的剂量经口灌注单独或与SNP（5mg/kg和10mg/kg体重）联合经口给药7天。PbAc损害了肾功能，通过增加血清尿素和肌酐水平，而SNP降低了这些水平，并有助于改善肾功能。SNP的给药通过增加PbAc诱导的抗氧化酶（SOD，CAT和GPx）活性和GSH水平，降低MDA水平（脂质过氧化的标记物），减少了氧化应激。SNP的给药降低了NF-κB、TNF-α、IL-1β、NLRP3和RAGE的mRNA转录水平，降低了NF-κB和TNF-α的蛋白水平，这些是PbAc引起的炎症反应参数之一。由于PbAc暴露导致抗凋亡蛋白Bcl-2的减少和凋亡相关蛋白Bax、APAF-1和Caspase-3的增加，SNP逆转了这种情况。SNP通过增加PbAc引起的PERK、IRE1、ATF-6、CHOP和GRP-78水平，减轻了ER应激。SNP通过降低PbAc增加的Beclin-1蛋白水平，减轻了自噬损伤。本研究的发现表明，SNP减轻了PbAc引起的肾毒性。© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Lead acetate (PbAc) is one of the top five most dangerous toxic heavy metals, particularly leading to kidney damage and posing serious health risks in both humans and animals. Sinapic acid (SNP) is a naturally occurring flavonoid found in fruits and vegetables that stands out with its antioxidant, anti-inflammatory, and anticancer properties. This is the first study to investigate the effects of SNP on oxidative stress, inflammation, apoptosis, autophagy and endoplasmic reticulum (ER) stress in PbAc-induced nephrotoxicity in rats by biochemical, molecular and histological methods. 35 Spraque dawley rats were randomly divided into five groups of 7 rats each: control, PbAc, SNP (10mg/kg), PbAc + SNP 5, PbAC + SNP 10. PbAc at a dose of 30 mg/kg body weight was administered via oral gavage alone or in combination with SNP (5 and 10 mg/kg body weight) via oral gavage for seven days. While PbAc impaired renal function by increasing serum urea and creatinine levels, SNP decreased these levels and contributed to the improvement in renal function. The administration of SNP reduced oxidative stress by increasing PbAc-induced decreased antioxidant enzyme (SOD, CAT, and GPx) activities and GSH levels, decreasing MDA levels, a marker of increased lipid peroxidation. SNP administration reduced NF-κB, TNF-α, IL-1β, NLRP3, and RAGE mRNA transcription levels, NF-κB, and TNF-α protein levels that are among the PbAc-induced increased inflammation parameters. Decreases in antiapoptotic Bcl-2 and increases in apoptotic Bax, APAF-1, and Caspase-3 due to PbAc exposure, SNP reversed the situation. SNP reduced ER stress caused by PbAc by increasing PERK, IRE1, ATF-6, CHOP, and GRP-78 levels and made it tend to regress. SNP reduced autophagy damage by decreasing the Beclin-1 protein level increased by PbAc. The findings of the present study suggested that SNP attenuates PbAc-induced nephrotoxicity.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.