N‑acetyl cysteine inhibits lipopolysaccharide‑induced apoptosis of human umbilical vein endothelial cells via the p38MAPK signaling pathway

Abstract

lipopolysaccharide (lPS) can regulate the expression of apoptotic factors, including caspase-3, Bcl-2 and Bcl-2-associated X protein (Bax). nitric oxide (no) plays an important role in apoptosis. n-acetyl cysteine (nac) has been shown to exhibit antioxidant effects in vitro. However, the effects of nac on lPS-induced apoptosis of human umbilical vein endothelial cells (HuVecs) and the associated mechanisms are not well characterized. The present study explored the effect of nac on lPS-induced apoptosis of HuVecs and determined the participation of the p38 mitogen-activated protein kinase (MaPK) pathway in the process of apoptosis. cell viability was assessed using the cell counting Kit-8 (ccK-8) assay. The expression of caspase-3, Bax, Bcl-2, phosphorylated (p)-p38MaPK/total (t-)p38MaPK and p-endothelial e nitric oxide synthase (enoS)/t-enoS proteins were determined by western blotting. The expression levels of caspase-3, Bax and Bcl-2 mrna were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The rate of apoptosis was determined using flow cytometry. an no detection kit (nitric reductase method) was used to determine no concentration. The results of ccK-8 and flow cytometric analyses showed that pretreatment of HuVecs with nac or p38MaPK inhibitor (SB203580) attenuated lPS-induced decrease in cell viability and increase in cell apoptosis. rT-qPcr and western blotting showed that lPS promoted caspase-3 and Bax expression, but inhibited that of Bcl-2 in HuVecs; however, these effects were attenuated by pretreatment with nac or SB203580. lPS stimulation significantly enhanced the expression of p-p38MAPK protein and reduced the expression of p-enoS protein; however, these effects were attenuated by pretreatment with nac or SB203580. nac pretreatment attenuated lPS-induced inhibition of no synthesis, which was consistent with the effects of SB203580. The results demonstrated that nac pretreatment alleviated lPS-induced apoptosis and inhibition of no production in HuVecs. Furthermore, these effects were proposed to be mediated via the p38MaPK signaling pathway.

Therapeutic efficacy ofN‐acetylcysteine and zinc sulphate against di‐(2‐ethylhexyl) phthalate‐induced testicular oxido‐nitrergic stress in male Wistar rat

“…Although, much has not been reported on effect of phthalates on sulphydryl, the result of the present study is an indication that DEHP may have caused the observed effect. This supports our hypothesis that oxido-nitrergic stress may serve as a common mediator of DEHP-cytotoxicity also purported by Huang et al (2010) and Amara et al (2020) NAC is a known precursor for GSH synthesis and scavenges ROS (Wang et al, 2014), an anti-inflammatory and antioxidant agent with the ability to inhibit NO production in several types of cells (Xiong et al, 2019). Similarly, it is known that zinc is one of the essential components of the body's most important natural antioxidant (Chian et al, 2000) and its sulphate is a potent anti-inflammatory and antioxidant agent.…”

“…NAC is a known precursor for GSH synthesis and scavenges ROS (Wang et al, 2014), an anti‐inflammatory and antioxidant agent with the ability to inhibit NO production in several types of cells (Xiong et al, 2019). Similarly, it is known that zinc is one of the essential components of the body's most important natural antioxidant (Chian et al, 2000) and its sulphate is a potent anti‐inflammatory and antioxidant agent.…”

Resveratrol Treats UVB-Induced Photoaging by Anti-MMP Expression, through Anti-Inflammatory, Antioxidant, and Antiapoptotic Properties, and Treats Photoaging by Upregulating VEGF-B Expression

“…The p38MAPK pathway is regulated through transcriptional and posttranscriptional mechanisms to affect cell death signaling as well as proapoptotic (Bax) and antiapoptotic (Bcl-2). Subsequently, the cystatin protease signaling pathway (caspase3) is altered as well, leading to apoptosis [ 15 ]. Therefore, targeting MAPK-regulated signaling pathways could potentially be an effective method in countering UVB-induced apoptosis.…”

The effects of N-acetylcysteine on ovulation and sex hormones profile in women with polycystic ovary syndrome: a systematic review and meta-analysis

“…As well, NAC supplementation increased levels of glutathione (GSH) in individuals with low GSH levels and improved redox homeostasis (54) . Moreover, ROS-induced mitogen-activated protein kinase (MAPK) activation could be inhibited by NAC (55) . Therefore, NAC, through decreasing lipid peroxidation, could have beneficial effects on reproductive biomarkers.…”