Abstract

Pentachlorophenol (PCP) is a chlorophenolic compound that is widely used as pesticide, biocide and as a wood preservative to treat utility poles and wharf pilings. PCP is rapidly absorbed through the gastrointestinal tract and enters the blood where it generates active oxygen species in target cells. We have, therefore, examined the protective effect of plant antioxidant 3,4-dihydroxybenzaldehyde (DHB) against PCP-induced cyto-and geno-toxicity in human red blood cells (RBC) and lymphocytes, respectively. Human RBC were incubated at 37°C with 0.75 mM PCP, either alone or in presence of different concentrations of DHB (0.05–2.0 mM). Several biochemical parameters were determined in whole cells and hemolysates. Incubation of RBC with PCP alone increased the formation of reactive oxygen and nitrogen species (ROS and RNS) that resulted in oxidation of proteins, lipids, cellular thiols and plasma membrane damage. The antioxidant defense system was impaired and glucose metabolism was inhibited. However, prior treatment of RBC with DHB lowered ROS and RNS generation and attenuated PCP-induced oxidative damage of cell components. DHB alone enhanced electron transport by the plasma membrane redox system and also prevented its inhibition by PCP. DHB significantly prevented PCP-induced transformation of RBC morphology from normal biconcave shape to spherocytes, spiculated acanthocytes and echinocytes. DHB protected human lymphocytes from PCP-induced DNA damage and strand breaks, lysosomal membrane damage and collapse of the mitochondrial membrane potential. These results show that DHB mitigates PCP-induced cytotoxicity and can potentially function as a chemoprotective agent against the harmful effects of PCP and possibly other chlorophenols.

摘要

五氯苯酚 (PCP) 是一种氯酚化合物，广泛用作杀虫剂、杀菌剂和木材防腐剂，用于处理电线杆和码头桩。五氯苯酚通过胃肠道迅速吸收并进入血液，在靶细胞中产生活性氧。因此，我们检测了植物抗氧化剂 3,4-二羟基苯甲醛 (DHB) 分别对人红细胞 (RBC) 和淋巴细胞中 PCP 诱导的细胞毒性和基因毒性的保护作用。人红细胞在 37°C 下与 0.75 mM PCP 一起孵育，单独或在不同浓度的 DHB（0.05–2.0 mM）存在下。在全细胞和溶血物中测定了几个生化参数。单独用 PCP 孵育 RBC 会增加活性氧和氮（ROS 和 RNS）的形成，从而导致蛋白质、脂质、细胞硫醇和质膜损伤的氧化。抗氧化防御系统受损，葡萄糖代谢受到抑制。然而，先前用 DHB 治疗 RBC 降低了 ROS 和 RNS 的产生，并减弱了 PCP 诱导的细胞成分氧化损伤。DHB 单独增强了质膜氧化还原系统的电子传输，也阻止了 PCP 对其的抑制。DHB 显着阻止了 PCP 诱导的红细胞形态从正常双凹形转变为球形红细胞、毛刺状棘红细胞和棘红细胞。DHB 保护人类淋巴细胞免受 PCP 诱导的 DNA 损伤和链断裂、溶酶体膜损伤和线粒体膜电位崩溃。