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双氯芬酸停药后生殖毒性作用增强:褪黑素治疗作用的研究

Elevated reproductive toxicity effects of diclofenac after withdrawal: Investigation of the therapeutic role of melatonin.

作者信息

Adeyemi Wale J, Omoniyi Julius A, Olayiwola Aluko, Ibrahim Mariam, Ogunyemi Olatinbo, Olayaki Luqman A

机构信息

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

出版信息

Toxicol Rep. 2019 Jun 14;6:571-577. doi: 10.1016/j.toxrep.2019.06.009. eCollection 2019.

DOI:10.1016/j.toxrep.2019.06.009
PMID:31293902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6595233/
Abstract

Although there are several reports on the toxic actions of sodium diclofenac (DF), there is dearth information on its effect on the male reproductive system. Therefore, the study investigated the effects of DF and melatonin in male rats. Twenty rats were used in this study, which lasted for 6 weeks. The control group (vehicle treated) received normal saline (0.1 ml/day, ). In the experimental groups, DF was administered during the first (group 2) and last (group 3) three weeks of the study. However, in group 4, melatonin was administered for 3 weeks, after 3 weeks of treatment with DF. DF and melatonin were administered at 1 and 10 mg/kg b.w./day () respectively. The results showed that unlike melatonin, DF had no effect on gonadotrophins; however, it caused significant decreases in GNRH and testosterone, but a significant increase in prolactin. Melatonin attenuated the pro-antioxidant and pro-inflammatory effects of DF, which caused significant decreases in SOD, TAC, CAT, but significant elevations in LDH, MDA, uric acid and CRP. Moreover, the hormone reversed the adverse effect of DF on sperm count, sperm motility and sperm morphology. There were slight evidence of the precipitation of imbalance in lipid metabolism by DF and the antidyslipidaemic action of melatonin. Compared to DF, DF recovery showed more adverse effects on prolactin, testosterone, LDH, MDA, UA, CRP, semen parameters (except sperm motility), TC, LDL-c, HDL-c and phospholipid. The histological results agreed with the biochemical assays. In conclusion, the reproductive toxicity effects of DF seem to escalate after withdrawal; however, these effects could be attenuated by treatment with melatonin.

摘要

尽管有几篇关于双氯芬酸钠(DF)毒性作用的报道,但关于其对雄性生殖系统影响的信息却很匮乏。因此,本研究调查了DF和褪黑素对雄性大鼠的影响。本研究使用了20只大鼠,为期6周。对照组(接受载体处理)给予生理盐水(0.1毫升/天)。在实验组中,在研究的前三周(第2组)和后三周(第3组)给予DF。然而,在第4组中,在DF治疗3周后给予褪黑素3周。DF和褪黑素分别以1毫克/千克体重/天和10毫克/千克体重/天的剂量给予。结果表明,与褪黑素不同,DF对促性腺激素没有影响;然而,它导致促性腺激素释放激素(GnRH)和睾酮显著降低,但催乳素显著升高。褪黑素减弱了DF的抗氧化和促炎作用,DF导致超氧化物歧化酶(SOD)、总抗氧化能力(TAC)、过氧化氢酶(CAT)显著降低,但乳酸脱氢酶(LDH)、丙二醛(MDA)、尿酸和C反应蛋白(CRP)显著升高。此外,该激素逆转了DF对精子数量、精子活力和精子形态的不利影响。有轻微证据表明DF会导致脂质代谢失衡,而褪黑素具有抗血脂异常作用。与DF相比,DF停药后对催乳素、睾酮、LDH、MDA、尿酸、CRP、精液参数(精子活力除外)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-c)、高密度脂蛋白胆固醇(HDL-c)和磷脂产生了更不利的影响。组织学结果与生化分析结果一致。总之,DF的生殖毒性作用在停药后似乎会加剧;然而,褪黑素治疗可以减轻这些影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/374b/6595233/3407f0261b2e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/374b/6595233/137eb166d4dc/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/374b/6595233/90a7f2776e9e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/374b/6595233/e4cc8390a5d6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/374b/6595233/3407f0261b2e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/374b/6595233/137eb166d4dc/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/374b/6595233/90a7f2776e9e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/374b/6595233/e4cc8390a5d6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/374b/6595233/3407f0261b2e/gr4.jpg

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