Probing the Cell Apoptosis Pathway Induced by Perfluorooctanoic Acid and Perfluorooctane Sulfonate at the Subcellular and Molecular Levels

Abstract

As typical perfluorinated compounds (PFCs), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been detected in various environmental media and their toxic effects have been extensively studied. Nevertheless, it remains unclear how PFCs cause cell apoptosis in healthy hepatocytes by inducing oxidative stress at the subcellular and molecular levels. In this study, the apoptotic pathways induced by PFOA and PFOS were explored. Besides, the effects of PFCs on the structure and function of lysozyme (LYZ) were investigated. After PFOA and PFOS exposure, the cell membrane and mitochondrial membrane potential were damaged. Further, PFOA and PFOS increased intracellular Ca2+ levels to 174.41 ± 1.70 and 158.91 ± 5.94%, respectively. Ultimately, caspase-3 was activated, causing cell apoptosis. As an indirect antioxidant enzyme, the molecular structure of LYZ was destroyed after interacting with PFOA and PFOS. Both PFOA and PFOS bound to the active center of LYZ, leading to the decrease of LYZ activity to 91.26 ± 0.78 and 76.01 ± 4.86%, respectively. This study demonstrates that PFOA and PFOS inhibit LYZ function, which can reduce the body’s ability to resist oxidative stress, and then lead to mitochondria-mediated apoptosis.

The structural and molecular mechanism of perfluorooctane sulfonate (PFOS)-induced toxicity on the rat myocardium's cytoarchitecture with the potential protective function of quercetin

“…This was corroborated by a histological study of the heart tissue in the PFOS group, which revealed darkly pigmented pyknotic nuclei in the cardiomyocytes. The apoptotic process, which appears to play a key part in PFOS toxicity, could explain this conclusion(Xu, Liu et al 2020). PFOS can cause apoptosis in murine N9 cells and upregulate the number of apoptotic cells in the liver of adult rats, according to Zhang et al(Zhang, Li et al 2011) ,which is consistent with our ndings.…”

Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome

“…Several studies have indicated that oxidative and inflammatory responses are involved in PFOS-induced cell injury and tissue damage. PFOS induces oxidative stress via inhibiting antioxidant factors (such as superoxide dismutase, lysozyme) or promoting reactive oxygen species in hepatocytes or endothelial cells, leading to cell death 11 , 13 , 14 , 16 , 17 . In addition, PFOS enhances the expression of proinflammatory cytokines (IL-1β, TNF-α, and IL-6) in macrophages 18 , 19 .…”

Perfluorooctane sulfonate induces heart toxicity involving cardiac apoptosis and inflammation in rats

“…The results of the present study suggested that PFOS at a dosage of 10 mg/kg could exert a pronounced cardiotoxicity in rats; however the mechanism underlying PFOS toxicity in the cardiovascular system remains unclear. Apoptosis is an important process in various human diseases and has been implicated in PFOS toxicity (34). A small number of basal studies have been carried out to examine the toxicity of PFOS associated with apoptosis (35)(36)(37).…”

“…Apoptosis is an important process in various human diseases and has been implicated in PFOS toxicity ( 34 ). A small number of basal studies have been carried out to examine the toxicity of PFOS associated with apoptosis ( 35-37 ).…”