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双氯芬酸所致肝毒性:低剂量ω-3脂肪酸具有更强的保护作用。

Diclofenac - induced hepatotoxicity: Low dose of omega-3 fatty acids have more protective effects.

作者信息

Adeyemi Wale Johnson, Olayaki Luqman Aribidesi

机构信息

Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.

出版信息

Toxicol Rep. 2017 Dec 16;5:90-95. doi: 10.1016/j.toxrep.2017.12.002. eCollection 2018.

DOI:10.1016/j.toxrep.2017.12.002
PMID:29854580
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5977161/
Abstract

The global embrace of the Western dietary style has necessitated the need for supplementation with omega-3 fatty acids (N-3) to redress the imbalance in omega-6/omega-3 fatty acids ratio. Therefore, the study investigated the effects of pre-treatment with N-3 in adult male Wistar rats exposed to diclofenac sodium (DF). Twenty adult male Wistar rats were used for this study. They were divided into 4 groups of 5 rats each, which included: Group 1 - Normal control; Group 2 - DF control; Group 3 - Low N-3 + DF; and, Group 4 - High N-3 + DF. The rats in group 2 were administered DF (10 mg/kg b.w./day, ) during the last 7 days of the experiment, while the rats in groups 3 and 4 were pre-treated with N-3 at 100 and 300 mg/kg b.w./day, respectively for 21 days, afterwards, they received DF at 10 mg/kg b.w./day () for 7 days. The result showed that DF significantly increased malondialdehyde, lactate dehydrogenase, and pro-inflammatory markers (total white blood cell count, uric acid, platelet/lymphocyte and neutrophil/lymphocyte ratios). Moreover, DF significantly elevated the activities of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, but, significant reduced the total antioxidant capacity and the activities of superoxide dismutase, catalase, and glutathione peroxidase. The histological results were parallel to the biochemical and haematological findings. Pre-treatment with N-3 significantly prevented the manifestation of the abnormalities brought about by DF. Although there were indications of the dose-dependent effects of N-3, the low dose was found to be more effective. In conclusion, the pre-administration of N-3, preferably at a low dose, could reduce hepatotoxicity that could result from subsequent exposure to DF.

摘要

全球对西方饮食方式的接受使得补充omega-3脂肪酸(N-3)成为必要,以纠正omega-6/omega-3脂肪酸比例的失衡。因此,本研究调查了N-3预处理对成年雄性Wistar大鼠暴露于双氯芬酸钠(DF)的影响。本研究使用了20只成年雄性Wistar大鼠。它们被分为4组,每组5只大鼠,包括:第1组 - 正常对照组;第2组 - DF对照组;第3组 - 低剂量N-3 + DF组;第4组 - 高剂量N-3 + DF组。第2组大鼠在实验的最后7天给予DF(10 mg/kg体重/天),而第3组和第4组大鼠分别以100和300 mg/kg体重/天的剂量预处理N-3 21天,之后,它们接受10 mg/kg体重/天的DF()7天。结果表明,DF显著增加了丙二醛、乳酸脱氢酶和促炎标志物(白细胞总数、尿酸、血小板/淋巴细胞和中性粒细胞/淋巴细胞比率)。此外,DF显著提高了丙氨酸转氨酶、天冬氨酸转氨酶和碱性磷酸酶的活性,但显著降低了总抗氧化能力以及超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性。组织学结果与生化和血液学结果一致。N-3预处理显著预防了DF引起的异常表现。尽管有迹象表明N-3存在剂量依赖性效应,但发现低剂量更有效。总之,预先给予N-3,最好是低剂量,可以降低随后接触DF可能导致的肝毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/4bde186db92d/gr7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/2549acf9be72/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/609ee44989f6/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/f80205ec1687/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/b682351a358c/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/4bde186db92d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/cc22a64eebd4/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/2b923d9f0f0c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/ac8c0625981d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/2549acf9be72/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/609ee44989f6/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/f80205ec1687/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/b682351a358c/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccde/5977161/4bde186db92d/gr7.jpg

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