Sener Göksel, Omurtag Gülden Z, Sehirli Ozer, Tozan Ayfer, Yüksel Meral, Ercan Feriha, Gedik Nursal
School of Pharmacy, Department of Pharmacology, Marmara University, Istanbul, Turkey.
Mol Cell Biochem. 2006 Feb;283(1-2):39-45. doi: 10.1007/s11010-006-2268-8.
The analgesic acetaminophen (AAP) causes a potentially fatal, hepatic centrilobular necrosis when taken in overdose. It was reported that these toxic effects of AAP are due to oxidative reactions that take place during its metabolism.
In this study, we aimed to investigate the possible beneficial effect of Ginkgo biloba (EGb), an antioxidant agent, against AAP toxicity in mice.
Balb/c mice were injected i.p. with: (1) vehicle, control (C) group; (2) a single dose of 50 mg/kg Ginkgo biloba extract, EGb group; (3) a single dose of 900 mg/kg i.p. acetaminophen, AAP group, and (4) EGb, in a dose of 50 mg/kg after AAP injection, AAP + EGb group. Serum ALT, AST, and tumor necrosis factor-alpha (TNF-alpha) levels in blood and glutathione (GSH), malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and collagen contents in liver tissues were measured. Formation of reactive oxygen species in hepatic tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lusigenin probe. Tissues were also examined microscopically.
ALT, AST levels, and TNF-alpha were increased significantly (p < 0.001) after AAP treatment, and reduced with EGb. Acetaminophen caused a significant (p < 0.05-0.001) decrease in GSH levels while MDA levels and MPO activity were increased (p < 0.001) in liver tissues. These changes were reversed by EGb treatment. Furthermore, luminol and lusigenin CL levels in the AAP group increased dramatically compared to control and reduced by EGb treatment (p < 0.01).
Our results implicate that AAP causes oxidative damage in hepatic tissues and Ginkgo biloba extract, by its antioxidant effects protects the tissues. Therefore, its therapeutic role as a "tissue injury-limiting agent" must be further elucidated in drug-induced oxidative damage.
对乙酰氨基酚（AAP）过量服用会导致潜在致命的肝小叶中心坏死。据报道，AAP的这些毒性作用是由于其代谢过程中发生的氧化反应所致。
在本研究中，我们旨在探讨抗氧化剂银杏叶提取物（EGb）对小鼠AAP毒性的可能有益作用。
将Balb/c小鼠腹腔注射：（1）溶剂，对照组（C）；（2）单剂量50mg/kg银杏叶提取物，EGb组；（3）单剂量900mg/kg腹腔注射对乙酰氨基酚，AAP组，以及（4）AAP注射后50mg/kg剂量的EGb，AAP+EGb组。检测血液中血清谷丙转氨酶（ALT）、谷草转氨酶（AST）和肿瘤坏死因子-α（TNF-α）水平以及肝组织中谷胱甘肽（GSH）、丙二醛（MDA）水平、髓过氧化物酶（MPO）活性和胶原蛋白含量。使用鲁米诺和光泽精探针通过化学发光（CL）技术监测肝组织样本中活性氧的形成。还对组织进行了显微镜检查。
AAP治疗后ALT、AST水平和TNF-α显著升高（p<0.001），而EGb使其降低。对乙酰氨基酚导致肝组织中GSH水平显著降低（p<0.05-0.001），而MDA水平和MPO活性升高（p<0.001）。EGb治疗可逆转这些变化。此外，与对照组相比，AAP组的鲁米诺和光泽精CL水平显著升高，而EGb治疗使其降低（p<0.01）。
我们的结果表明，AAP会导致肝组织氧化损伤，而银杏叶提取物通过其抗氧化作用保护组织。因此，其作为“组织损伤限制剂”在药物诱导的氧化损伤中的治疗作用必须进一步阐明。
