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质子泵抑制剂对男性生育能力的有害影响:来自埃索美拉唑和兰索拉唑对Wistar大鼠亚慢性毒性研究的证据。

Harmful Consequences of Proton Pump Inhibitors on Male Fertility: An Evidence from Subchronic Toxicity Study of Esomeprazole and Lansoprazole in Wistar Rats.

作者信息

Mumtaz Namra, Akhtar Muhammad Furqan, Saleem Ammara, Riaz Amjad

机构信息

Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, Pakistan.

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan.

出版信息

Int J Endocrinol. 2022 Apr 28;2022:4479261. doi: 10.1155/2022/4479261. eCollection 2022.

DOI:10.1155/2022/4479261
PMID:35529080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9072022/
Abstract

Proton pump inhibitors (PPIs) are frequently prescribed as gastric acid-suppressing agents. Nevertheless, there is limited evidence supporting the risk of detrimental effects of PPIs on male fertility. The purpose of the current study was to evaluate the effect of subchronic use of proton pump inhibitors on male fertility. Seventy adult male Wistar rats were assigned into seven groups. The normal control group orally received solvent only. Groups 2, 3, and 4 were orally given esomeprazole while groups 5, 6, and 7 received lansoprazole at 2.5, 5, and 10 mg/kg/day, respectively. After 45 days of treatment, blood samples, epididymis, and testis were collected. Sperm count, motility, and morphology were determined. The level of hormones such as testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) and oxidative status of testis tissue, such as superoxide dismutase, catalase, reduced glutathione, malondialdehyde (MDA), and nitric oxide (NO) were estimated. Results demonstrated a significant decline in sperm count, motility, morphology, testosterone, and catalase at 10 mg/kg/day and GSH at 2.5 mg/kg/day. A significant increase in FSH, LH, and MDA at 10 mg/kg/day and NO at 2.5 mg/kg/day was found as compared to the control group. The pathological alterations specifically dilation of Leydig cells, vacuolization, and degeneration of the seminiferous tubules were also evident. It is concluded that PPIs had caused male reproductive toxicity in Wistar rats due to altered levels of hormones such as testosterone, FSH, and LH, elevated levels of NO, and oxidative stress.

摘要

质子泵抑制剂(PPIs)常被用作胃酸抑制剂。然而,支持PPIs对男性生育产生有害影响风险的证据有限。本研究的目的是评估亚慢性使用质子泵抑制剂对男性生育能力的影响。将70只成年雄性Wistar大鼠分为7组。正常对照组仅口服溶剂。第2、3和4组口服埃索美拉唑,而第5、6和7组分别以2.5、5和10mg/kg/天的剂量接受兰索拉唑。治疗45天后,采集血液样本、附睾和睾丸。测定精子数量、活力和形态。评估睾酮、促卵泡激素(FSH)和促黄体生成素(LH)等激素水平以及睾丸组织的氧化状态,如超氧化物歧化酶、过氧化氢酶、还原型谷胱甘肽、丙二醛(MDA)和一氧化氮(NO)。结果表明,在10mg/kg/天剂量下精子数量、活力、形态、睾酮和过氧化氢酶显著下降,在2.5mg/kg/天剂量下谷胱甘肽显著下降。与对照组相比,在10mg/kg/天剂量下FSH、LH和MDA显著增加,在2.5mg/kg/天剂量下NO显著增加。睾丸间质细胞的特异性扩张、空泡化和生精小管的变性等病理改变也很明显。结论是,由于睾酮、FSH和LH等激素水平改变、NO水平升高以及氧化应激,PPIs在Wistar大鼠中导致了雄性生殖毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8156/9072022/b4793491a58d/IJE2022-4479261.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8156/9072022/11a577f0c163/IJE2022-4479261.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8156/9072022/b4793491a58d/IJE2022-4479261.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8156/9072022/11a577f0c163/IJE2022-4479261.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8156/9072022/11630adce61c/IJE2022-4479261.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8156/9072022/45012d7c85f0/IJE2022-4479261.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8156/9072022/0afdcdaa6fdb/IJE2022-4479261.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8156/9072022/b2d02dbc2785/IJE2022-4479261.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8156/9072022/b4793491a58d/IJE2022-4479261.006.jpg

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