Maheshwari Nikhil, Mahmood Riaz
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India.
Drug Chem Toxicol. 2022 May;45(3):1225-1242. doi: 10.1080/01480545.2020.1811722. Epub 2020 Aug 28.
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.
五氯苯酚(PCP)是一种氯酚类化合物,被广泛用作杀虫剂、杀菌剂以及用于处理电线杆和码头桩柱的木材防腐剂。PCP可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,我们分别研究了植物抗氧化剂3,4 - 二羟基苯甲醛(DHB)对PCP诱导的人红细胞(RBC)和淋巴细胞的细胞毒性和基因毒性的保护作用。将人红细胞在37°C下与0.75 mM的PCP单独孵育,或在不同浓度(0.05 - 2.0 mM)的DHB存在下孵育。测定了全细胞和溶血产物中的几个生化参数。单独用PCP孵育人红细胞会增加活性氧和氮物种(ROS和RNS)的形成,导致蛋白质、脂质、细胞硫醇氧化以及质膜损伤。抗氧化防御系统受损,葡萄糖代谢受到抑制。然而,用DHB预先处理红细胞可降低ROS和RNS的产生,并减轻PCP诱导的细胞成分氧化损伤。单独的DHB可通过质膜氧化还原系统增强电子传递,并防止其被PCP抑制。DHB显著防止了PCP诱导的红细胞形态从正常双凹形转变为球形细胞、棘状刺细胞和棘红细胞。DHB保护人淋巴细胞免受PCP诱导的DNA损伤和链断裂、溶酶体膜损伤以及线粒体膜电位崩溃。这些结果表明,DHB减轻了PCP诱导的细胞毒性,并可能作为一种化学保护剂来对抗PCP以及可能其他氯酚的有害影响。