Departments of Toxicology and Narcotics, Medical Biochemistry, Pharmacology, and Pathology, National Research Centre, Cairo, Egypt.
Eur Rev Med Pharmacol Sci. 2013 Mar;17(6):735-44.
The aim of the present study was to investigate the effect of the serotonin selective reuptake inhibitors (SSRIs) fluoxetine and sertraline and the tricyclic drug imipramine on oxidative stress in the brain and liver caused by thioacetamide in rats.
Drugs were administered orally once daily at doses of 10 and 20 mg/kg for two weeks prior to intraperitoneal injection of thioacetamide (300 mg/kg). Rats were euthanized 24 h after thioacetamide. Reduced glutathione (GSH), malondialdehyde (MDA) and nitric oxide were measured in brain and liver. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured in serum and histopathological evaluation of liver injury was performed.
The administration of thioacetamide increased MDA by 151.8% and 161.2%, increased nitric oxide by 57.2% and 63.9% and decreased GSH by -40.6% and -67% in the brain and liver, respectively. Thioacetamide markedly increased serum ALT, AST and ALP by 277.8, 80.8 and 121%, respectively. In the brain, MDA was decreased in rats treated with fluoxetine or sertraline. The level of GSH increased by fluoxetine and by the higher dose of sertraline. Nitric oxide in brain was unchanged by fluoxetine, but increased after sertraline at 20 mg/kg. Brain MDA was increased by imipramine, which also decreased brain nitrite level. In the liver, fluoxetine or sertraline treatment increased GSH and nitrite levels. MDA was also increased by either drug. The drugs markedly decreased ALT, but increased ALP in serum. Meanwhile, imipramine decreased liver nitric oxide levels (at the lower dose only -32.9%), markedly increased hepatic GSH, but did not change MDA level. Serum ALT decreased by imipramine (but AST and ALP showed no change). Histopathological and histochemical examinations indicated that thioacetamide-induced liver injury was not decreased after treatment with the antidepressant drugs.
In thioacetamide-treated rats, pretreatment with the SSRIs drugs fluoxetine and sertraline is associated with decreased lipid peroxidation in brain; liver peroxidation, however, is increased. Imipramine displayed opposite effects. The thioacetamide-induced hepatic damage was not reduced by fluoxetine, sertraline or imipramine.
本研究旨在探讨选择性 5-羟色胺再摄取抑制剂（SSRIs）氟西汀和舍曲林以及三环类药物丙咪嗪对硫代乙酰胺引起的大鼠脑和肝氧化应激的影响。
药物以 10 和 20mg/kg 的剂量每天口服一次，在腹腔注射硫代乙酰胺（300mg/kg）前两周给药。硫代乙酰胺给药 24 小时后处死大鼠。测定脑和肝中的还原型谷胱甘肽（GSH）、丙二醛（MDA）和一氧化氮。测定血清中天冬氨酸转氨酶（ALT）、丙氨酸转氨酶（AST）和碱性磷酸酶（ALP），并对肝损伤进行组织病理学评价。
硫代乙酰胺使脑和肝中的 MDA 分别增加 151.8%和 161.2%，使一氧化氮分别增加 57.2%和 63.9%，使 GSH 分别减少-40.6%和-67%。硫代乙酰胺使血清 ALT、AST 和 ALP 分别增加 277.8、80.8 和 121%。氟西汀或舍曲林治疗使脑 MDA 降低。氟西汀和较高剂量的舍曲林使脑 GSH 增加。氟西汀对脑一氧化氮无影响，但舍曲林 20mg/kg 后增加。丙咪嗪使脑 MDA 增加，同时降低脑亚硝酸盐水平。氟西汀或舍曲林治疗使肝 GSH 和亚硝酸盐水平升高。两种药物均使 MDA 增加。这些药物显著降低血清 ALT，但增加 ALP。同时，丙咪嗪降低肝一氧化氮水平（仅低剂量组-32.9%），显著增加肝 GSH，但不改变 MDA 水平。丙咪嗪降低血清 ALT（但 AST 和 ALP 无变化）。组织病理学和组织化学检查表明，抗抑郁药治疗后，硫代乙酰胺诱导的肝损伤并未减轻。
在硫代乙酰胺处理的大鼠中，SSRIs 氟西汀和舍曲林的预处理与脑脂质过氧化减少有关；然而，肝过氧化增加。丙咪嗪表现出相反的效果。氟西汀、舍曲林或丙咪嗪未减轻硫代乙酰胺引起的肝损伤。
