Abdel-Wahab Mohamed H, Arafa Hossam M M, El-Mahdy Mohamad A, Abdel-Naim Ashraf B
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
Pharmacol Res. 2002 Sep;46(3):287-93. doi: 10.1016/s1043-6618(02)00093-2.
Dibromoacetonitrile (DBAN) is a disinfection by-product following chlorination of drinking water. Epidemiological studies indicate that it might present a potential hazard to human health. DBAN was previously found to induce oxidative stress in rat stomach as manifested by perturbation of some enzymatic and nonenzymatic antioxidant parameters. Therefore, we have investigated the oxidative stress possibly induced by DBAN in mouse stomach and possible protection by melatonin (MLT) as a free radical scavenger. In a dose-response study, mice were administered a single oral dose of DBAN (30, 60 and 120 mg kg(-1)) and were sacrificed after 1 h. DBAN significantly reduced glutathione (GSH) content that was somehow dose-related, and inhibited glutathione-S-transferase (GST) activity in gastric tissues. The highest dose of DBAN (120 mg kg(-1)) lowered GSH by 74% and induced a significant elevation of lipid peroxidation products, determined as thiobarbituric acid reactive substances (TBARS) by 69%. The same dose inhibited the gastric activities of GST, superoxide dismutase (SOD) and catalase (CAT) by 70, 57 and 23%, respectively. In a time-course study, mice were administered DBAN (60 mg kg(-1) p.o.) and sacrificed 0.5, 1, 3, 6, 12 and 24 h after treatment. GSH was dramatically depleted at 0.5, 1, 3 and 6 h (45, 38, 39 and 49% of control, respectively) and remained significantly low at 12 and 24 h. Also, DBAN caused an accumulation of TBARS in gastric tissues starting from 3 h and was maximum at 6 h (133% of the control). The enzymatic activities of GST and SOD were maximally inhibited by DBAN treatment at 0.5 h (32% for GST and 37% for SOD of the respective control). The activities of both enzymes returned to control values at 24 h. CAT activity was not affected by DBAN administration at all. Pretreatment of another group of mice with melatonin (10 mg kg(-1) per day p.o. 12 days) before administration of DBAN (60 mg kg(-1) p.o.) completely mitigated the aforementioned parameters. In conclusion, the present study indicates that DBAN induces a marked oxidative stress in mouse stomach as evidenced by GSH depletion, TBARS accumulation and GST, SOD and CAT inhibition. Melatonin could mitigate DBAN-induced oxidative stress in mouse stomach as it did almost normalize both the enzymatic and nonenzymatic antioxidant parameters.
二溴乙腈（DBAN）是饮用水氯化消毒后的一种副产物。流行病学研究表明，它可能对人类健康构成潜在危害。此前发现DBAN可诱导大鼠胃内的氧化应激，表现为一些酶促和非酶促抗氧化参数的紊乱。因此，我们研究了DBAN可能在小鼠胃内诱导的氧化应激以及褪黑素（MLT）作为自由基清除剂可能提供的保护作用。在一项剂量反应研究中，给小鼠单次口服DBAN（30、60和120 mg kg⁻¹），1小时后处死。DBAN显著降低了谷胱甘肽（GSH）含量，且在一定程度上与剂量相关，并抑制了胃组织中的谷胱甘肽 - S - 转移酶（GST）活性。DBAN的最高剂量（120 mg kg⁻¹）使GSH降低了74%，并使脂质过氧化产物（以硫代巴比妥酸反应性物质（TBARS）测定）显著升高了69%。相同剂量分别抑制了胃组织中GST、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性70%、57%和23%。在一项时间进程研究中，给小鼠口服DBAN（60 mg kg⁻¹），在处理后0.5、1、3、6、12和24小时处死。GSH在0.5、1、3和6小时显著减少（分别为对照组的45%、38%、39%和49%），在12和24小时仍显著低于对照组。此外，DBAN从3小时开始导致胃组织中TBARS积累，在6小时达到最大值（为对照组的133%）。DBAN处理在0.5小时对GST和SOD的酶活性抑制最大（GST为各自对照组的32%，SOD为37%）。两种酶的活性在24小时恢复到对照值。CAT活性完全不受DBAN给药的影响。另一组小鼠在给予DBAN（60 mg kg⁻¹）前用褪黑素（每天口服10 mg kg⁻¹，共12天）预处理，可完全减轻上述参数的变化。总之，本研究表明DBAN在小鼠胃内诱导了明显的氧化应激，表现为GSH耗竭、TBARS积累以及GST、SOD和CAT抑制。褪黑素可减轻DBAN诱导的小鼠胃内氧化应激，因为它几乎使酶促和非酶促抗氧化参数均恢复正常。
