Department of Pharmacology, School of Veterinary, Shiraz University, Iran; Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Department of Pharmacology, School of Veterinary, Shiraz University, Iran.
Food Chem Toxicol. 2018 Oct;120:571-577. doi: 10.1016/j.fct.2018.07.061. Epub 2018 Aug 3.
Use of lead-adulterated opium has become one of the major sources of lead poisoning in Iran. This study was designed to assess clinical effects and oxidative stress and its association with GSTM1, GSTT1, NQO1, and ALAD genes polymorphisms and blood lead level (BLL) in lead-adulterated opium users. The oxidative stress status in 192 opium users with lead poisoning symptoms measured and compared with 102 healthy individuals. Gluthatione S-transferase (GST)-M1 and -T1 genes deletion, NQO1 rs1800566, and δ-aminolevulinic acid dehydratase (ALAD) rs1800435 polymorphisms were determined using PCR and PCR-RFLP. The relation between the polymorphisms, BLL, and oxidative stress parameters were analysed using multivariate linear regressions. The common symptoms of lead toxicity were gastrointestinal and neurologic complications. Oxidative stress was significantly higher in opium addicts and lipid peroxidation significantly correlated with BLL. There was significant association between ALAD rs1800435 and BLL, and the BLL was significantly lower in the patients with ALAD 1-2 genotype. Use of lead-adulterated opium causes high frequency of lead toxicity symptoms, hematological and biochemical abnormalities, and oxidative stress which are associated with BLL. Route of opioid use and the polymorphism of rs1800435 in ALAD gene are the major determinants of BLL in lead-adulterated opium users.
在伊朗，使用含铅鸦片已成为铅中毒的主要来源之一。本研究旨在评估含铅鸦片使用者的临床效应、氧化应激及其与 GSTM1、GSTT1、NQO1 和 ALAD 基因多态性和血铅水平 (BLL) 的关系。测量了 192 名有铅中毒症状的鸦片使用者的氧化应激状态，并与 102 名健康个体进行了比较。使用 PCR 和 PCR-RFLP 确定谷胱甘肽 S-转移酶 (GST)-M1 和 -T1 基因缺失、NQO1 rs1800566 和 δ-氨基酮戊酸脱水酶 (ALAD) rs1800435 多态性。使用多元线性回归分析多态性、BLL 和氧化应激参数之间的关系。铅中毒的常见症状是胃肠道和神经并发症。鸦片成瘾者的氧化应激明显升高，脂质过氧化与 BLL 显著相关。ALAD rs1800435 与 BLL 之间存在显著关联，并且具有 ALAD 1-2 基因型的患者的 BLL 明显较低。使用含铅鸦片会导致铅中毒症状、血液和生化异常以及氧化应激的高频率发生，这些都与 BLL 有关。阿片类药物使用途径和 ALAD 基因 rs1800435 多态性是含铅鸦片使用者 BLL 的主要决定因素。
