The inhibitory effect of Yam polysaccharides on acrylamide‐induced programmed cell death in RAW 264.7 cells

Abstract

Acrylamide has been well known for its neurotoxicity, genotoxicity, carcinogenicity, etc. Recently, the immunotoxicity of acrylamide has been reported by different research groups, although the underlying mechanisms of acrylamide endangering immune systems have not been fully elucidated. In this study, mouse monocyte–macrophage cells model was used to clarify the toxic mechanism of acrylamide and the inhibitory effect of Yam polysaccharides (YPS) on acrylamide‐induced damage. We found that acrylamide induced RAW 264.7 cell death in a time‐ and concentration‐dependent manner. After acrylamide (2.0, 3.0, 4.0 mmol/L) treatment for 24 h, cell apoptosis, autophagy, and pyroptosis were observed. However, the levels of autophagy and pyroptosis decreased at a high concentration of acrylamide (4.0 mmol/L). Acrylamide upregulated P2X7 expression, but the P2X7 level was not showing a monotone increasing trend. When the P2X7 antagonist was applied, the effect of acrylamide on autophagy and pyroptosis was weakened. Additionally, acrylamide triggered the occurrence of oxidative stress and a decreased nitric oxide (NO) level. However, reactive oxygen species (ROS) generation, the decrease of heme oxygenase‐1 (HO‐1) expression, and the increase of inducible nitric oxide synthase (iNOS) expression were reversed by the inhibition of P2X7. Yam polysaccharides (50.0 μg/ml) significantly inhibited acrylamide‐induced oxidative stress and cell death (including apoptosis, autophagy, and pyroptosis). Yam polysaccharides also effectively reversed the increase of iNOS expression induced by acrylamide. However, Yam polysaccharides promoted the expression of P2X7 rather than prohibit it. These results indicated that acrylamide caused RAW 264.7 cell death due to pro‐apoptosis as well as excessive autophagy and pyroptosis. Apoptosis might be more predominant than autophagy and pyroptosis under a higher concentration of acrylamide (4.0 mmol/L). P2X7‐stimulated oxidative stress was responsible for acrylamide‐induced programmed cell death (PCD), but P2X7 showed limited regulatory effect on apoptosis. Yam polysaccharides with antioxidant activity inhibited acrylamide‐induced cell death (apoptosis, autophagy, and pyroptosis), but exerted limited effect on the acrylamide‐induced P2X7 expression. These findings would offer an insight into elucidating the immunotoxic mechanism of acrylamide and the potential approaches to control its toxicity.

Curcumin mitigates acrylamide‐induced ovarian antioxidant disruption and apoptosis in female Balb/c mice: A comprehensive study on gene and protein expressions

“…These enzymes, namely SOD, CAT, and GPX, work to convert harmful superoxide anion (*O2), hydrogen peroxides (H 2 O 2 ), hydroperoxide, and lipid peroxides into less harmful and non-toxic molecules, such as H 2 O, O 2 , and corresponding alcohols(Alaee et al, 2023;Ighodaro & Akinloye, 2018).Reproductive toxicity induced by ACR has been extensively documented in various studies. Consistent with our findings, Hamdy et al (2017) reported significant decreases in ovarian catalase (Cat) activity, superoxide dismutase (SOD) activity, reduced glutathione (GSH) levels, and glutathione peroxidase (GSH-Px) activity in female rats exposed to ACR(Hamdy et al, 2017).Wang et al demonstrated that acrylamide induces oxidative stress, resulting in reduced nitric oxide (NO) levels, with observed consequences including the inhibition of cell growth and the induction of cell death(Wang et al, 2023). Furthermore, Seberi et al illustrated a noteworthy increase in malondialdehyde (MDA) concentration and a significant decrease in total antioxidant capacity in the blood of female NMRI mice sub-…”

“…Wang et al. demonstrated that acrylamide induces oxidative stress, resulting in reduced nitric oxide (NO) levels, with observed consequences including the inhibition of cell growth and the induction of cell death (Wang et al., 2023 ).…”

The effects of Yam polysaccharides on acrylamide-induced RAW264.7 cell polarization

“…Moreover, in vivo studies have recently revealed that the intake of acrylamide induced splenic damages in adult zebrafish, and caused reduction of natural killer (NK) cells in female BALB/c mice (Fang et al, 2014;Komoike et al, 2020). Additionally, our research indicated that acrylamide caused RAW264.7 cell disfunction and death due to excessive autophagy, pyroptosis and oxidative stress (Wang et al, 2023). These findings demonstrated that acrylamide can cause immunotoxicity.…”

The role of microRNAs in acrylamide toxicity

“…One study noted a significant inhibition at a concentration of 4.0 mmol/L for 12 h (90.2 ± 4.5%) or 2.0 mmol/L for 24 h (87.7 ± 4.4%). Furthermore, the cell count notably dropped to less than 30% following exposure to concentrations exceeding 6.0 mmol/L of acrylamide for 24 h. The IC50 value of acrylamide in RAW 264.7 cells was determined to be 4.9 mmol/L after 24 h (62). A preceding (63).…”

“…One study noted a significant inhibition at a concentration of 4.0 mmol/L for 12 h (90.2 ± 4.5%) or 2.0 mmol/L for 24 h (87.7 ± 4.4%). Furthermore, the cell count notably dropped to less than 30% following exposure to concentrations exceeding 6.0 mmol/L of acrylamide for 24 h. The IC50 value of acrylamide in RAW 264.7 cells was determined to be 4.9 mmol/L after 24 h ( 62 ). A preceding investigation demonstrated that the treatment of Caco-2 cells with AA (ranging from 0.2 to 50 mM) resulted in a decline in cell viability that was both time- and dose-dependent over 24 to 72 h. At the highest AA concentration (50 mM), cytotoxicity exceeded 84.0%–94.4% in the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and 78.4%–82.2% in the PrestoBlue assay after exposure for 24–72 h ( 63 ).…”