Xu Dongmin, Li Li, Tang Leilei, Guo Ming, Yang Jie
Department of Pharmacy, Chun'an First People's Hospital, Zhejiang Province People's Hospital Chun'an Branch, Hangzhou, Zhejiang 311700, P.R. China.
Department of Pharmacy, Zhejiang Xiaoshan Hospital, Hangzhou, Zhejiang 311200, P.R. China.
Exp Ther Med. 2022 Jan;23(1):14. doi: 10.3892/etm.2021.10936. Epub 2021 Oct 28.
Perfluorooctane sulfonate (PFOS) is a persistent pollutant that exerts toxicity and induces cardiogenesis in humans and animals. Yet, the effect of PFOS exposure on cardiac toxicity in adult rats has, to our knowledge, not been reported and the mechanism still remains unknown. The present study aimed to investigate the toxicity of PFOS on rat hearts and any associated mechanisms. Rats were exposed to 0 (control), 1 and 10 mg/kg PFOS every other day for 14 days. Body weight and heart weight were recorded. The serum levels of lactic dehydrogenase (LDH), creatine kinase (CK), creatine kinase-isoenzyme-MB (CK-MB) and cardiac troponin-T (cTn-T) in heart tissues were measured using biochemical assays. TUNEL staining and western blotting were applied to analyze levels of apoptosis in rat hearts. Pathological assessment and immunohistochemistry analysis of heart tissues were used to evaluate the levels of PFOS-induced cardiotoxicity and inflammatory infiltration. PFOS exposure at the dosage of 10 mg/kg significantly increased the percentage of heart to body weight; however, it did not alter the body weight. At 10 mg/kg, PFOS significantly increased expression levels of myocardial injury markers, such as cTn-T, LDH, CK and CK-MB, while 1 mg/kg PFOS upregulated the expression level of cTn-T in rats. Notably, cardiac fibrosis and myocardiac hypertrophy appeared in the 10 mg/kg PFOS group. In addition, TUNEL-positive cells were significantly increased by exposure to 10 mg/kg PFOS in rat heart tissues. The protein expressions profiles of p53 and Bax were also significantly upregulated in the 10 mg/kg PFOS group. Inflammatory infiltration, detected by anaylzing expression levels of IL-1β and TNF-α, was significantly raised by 10 mg/kg PFOS exposure. In conclusion, these results demonstrated that 10 mg/kg PFOS-induced cardiac toxicity in rats, which was associated with an increase in apoptosis and the expression of proinflammatory cytokines.
全氟辛烷磺酸(PFOS)是一种持久性污染物,对人类和动物具有毒性并可诱导心脏发生。然而,据我们所知,PFOS暴露对成年大鼠心脏毒性的影响尚未见报道,其机制仍然未知。本研究旨在探讨PFOS对大鼠心脏的毒性及其相关机制。大鼠每隔一天分别暴露于0(对照)、1和10 mg/kg的PFOS中,持续14天。记录体重和心脏重量。使用生化测定法测量心脏组织中乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶-MB(CK-MB)和心肌肌钙蛋白-T(cTn-T)的血清水平。采用TUNEL染色和蛋白质印迹法分析大鼠心脏中的凋亡水平。对心脏组织进行病理评估和免疫组织化学分析,以评估PFOS诱导的心脏毒性和炎症浸润水平。10 mg/kg剂量的PFOS暴露显著增加了心脏重量与体重的百分比;然而,它并未改变体重。在10 mg/kg时,PFOS显著增加了心肌损伤标志物如cTn-T、LDH、CK和CK-MB的表达水平,而1 mg/kg的PFOS上调了大鼠cTn-T的表达水平。值得注意的是,10 mg/kg PFOS组出现了心脏纤维化和心肌肥大。此外,暴露于10 mg/kg PFOS的大鼠心脏组织中TUNEL阳性细胞显著增加。10 mg/kg PFOS组中p53和Bax的蛋白质表达谱也显著上调。通过分析IL-1β和TNF-α的表达水平检测到的炎症浸润在10 mg/kg PFOS暴露下显著增加。总之,这些结果表明,10 mg/kg的PFOS可诱导大鼠心脏毒性,这与细胞凋亡增加和促炎细胞因子的表达有关。