Department of Microbiology, Immunology and Infectious Diseases, College of Medicine and Medical Sciences, Arabian Gulf University, Manama 329, Bahrain.
Toxins (Basel). 2023 Jan 4;15(1):38. doi: 10.3390/toxins15010038.
Background: Panton−Valentine Leukocidin sustains a strong cytotoxic activity, targeting immune cells and, consequently, perforating the plasma membrane and inducing cell death. The present study is aimed to examine the individual effect of ascorbic acid and nicotinamide on PVL cytotoxicity ex vivo, as well as their effect on granulocytes viability when treated with PVL. Materials and Methods: The PVL cytotoxicity assay was performed in triplicates using the commercial Cytotoxicity Detection Kit PLUS (LDH). LDH release was measured to determine cell damage and cell viability was measured via flow cytometry. Results and discussion: A clear reduction in PVL cytotoxicity was demonstrated (p < 0.001). Treatment with ascorbic acid at 5 mg/mL has shown a 3-fold reduction in PVL cytotoxicity; likewise, nicotinamide illustrated a 4-fold reduction in PVL cytotoxicity. Moreover, granulocytes’ viability after PVL treatment was maintained when incubated with 5 mg/mL of ascorbic acid and nicotinamide. Conclusions: our findings illustrated that ascorbic acid and nicotinamide exhibit an inhibitory effect on PVL cytotoxicity and promote cell viability, as the cytotoxic effect of the toxin is postulated to be neutralized by antioxidant incubation. Further investigations are needed to assess whether these antioxidants may be viable options in PVL cytotoxicity attenuation in PVL-associated diseases.
Panton-Valentine Leukocidin(PVL)具有很强的细胞毒性作用,靶向免疫细胞,从而穿孔质膜并诱导细胞死亡。本研究旨在探讨抗坏血酸和烟酰胺对 PVL 细胞毒性的个体影响,以及它们在治疗 PVL 时对粒细胞活力的影响。
使用商业细胞毒性检测试剂盒 PLUS(LDH)重复进行了 PVL 细胞毒性测定。通过测量 LDH 释放来确定细胞损伤,通过流式细胞术测量细胞活力。
结果表明,PVL 细胞毒性明显降低(p < 0.001)。用 5mg/mL 的抗坏血酸处理显示出 3 倍的 PVL 细胞毒性降低;同样,烟酰胺也显示出 4 倍的 PVL 细胞毒性降低。此外,当用 5mg/mL 的抗坏血酸和烟酰胺孵育时,经 PVL 处理后的粒细胞活力得以维持。
我们的研究结果表明,抗坏血酸和烟酰胺对 PVL 细胞毒性具有抑制作用,并促进细胞活力,因为推测毒素的细胞毒性作用通过抗氧化剂孵育被中和。需要进一步的研究来评估这些抗氧化剂是否可作为治疗 PVL 相关疾病中减轻 PVL 细胞毒性的可行选择。