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非诺贝特改善了阿托伐他汀和胡椒碱诱导的雄性Wistar大鼠的活性氧介导的生殖毒性。

Fenofibrate ameliorated atorvastatin and piperine-induced ROS mediated reproductive toxicity in male Wistar rats.

作者信息

Ghosh Sanjib, Sarkar Sweata, Biswas Maharaj

机构信息

Endocrinology Laboratory, Department of Zoology, University of Kalyani, West Bengal 741235, India.

Department of Zoology (PG Studies), Rishi Bankim Chandra College, West Bengal 743165, India.

出版信息

Toxicol Rep. 2024 Dec 10;14:101861. doi: 10.1016/j.toxrep.2024.101861. eCollection 2025 Jun.

DOI:10.1016/j.toxrep.2024.101861
PMID:39758804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11699439/
Abstract

Atorvastatin and fenofibrate are well-known lipid-lowering drugs. Atorvastatin acts by reducing the production of cholesterol through the inhibition of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG Co-A reductase) enzyme, whereas fenofibrate is a PPAR-α agonist. Piperine is an alkaloid mostly found in black pepper fruits. The present study was planned to evaluate the activities of atorvastatin, fenofibrate, and piperine on the male reproductive system. A total of 35 male Wistar rats were obtained for the experiment. Rats were randomly divided into 7 groups, each group with 5 rats. The experiment was run for 28 days. Group I rat got normal meals for 28 days; Group II received atorvastatin (08 mg/kg/day); Group III received piperine (10 mg/kg/day); and Group IV received fenofibrate (20 mg/kg/day). Group V received atorvastatin (8 mg/kg/day) and piperine (10 mg/kg/day); Group VI received piperine (10 mg/kg/day) and fenofibrate (20 mg/kg/day). VII received fenofibrate (20 mg/kg bw/day) and atorvastatin (8 mg/kg/day). After sacrifice, serum and testicular cholesterol and testosterone levels assessed by ELISA, ROS generation analysed by using flow cytometry, MDA, SOD, and catalase were measured. Histological, sperm-parameter analysis, and spermatogenic evaluations were also done. Activities of atorvastatin and piperine revealed reproductive toxicity upon treatment. Fenofibrate treatment, along with atorvastatin and piperine, showed protective effects. In conclusion, atorvastatin and piperine affected reproductive potential, whereas fenofibrate might have protective efficacy against atorvastatin and piperine-induced reproductive toxicity.

摘要

阿托伐他汀和非诺贝特是著名的降脂药物。阿托伐他汀通过抑制3-羟基-3-甲基戊二酰辅酶A还原酶(HMG Co-A还原酶)来减少胆固醇的生成,而非诺贝特是一种过氧化物酶体增殖物激活受体-α(PPAR-α)激动剂。胡椒碱是一种主要存在于黑胡椒果实中的生物碱。本研究旨在评估阿托伐他汀、非诺贝特和胡椒碱对雄性生殖系统的影响。总共获得35只雄性Wistar大鼠用于实验。大鼠被随机分为7组,每组5只。实验持续28天。第一组大鼠28天给予正常饮食;第二组给予阿托伐他汀(08毫克/千克/天);第三组给予胡椒碱(10毫克/千克/天);第四组给予非诺贝特(20毫克/千克/天)。第五组给予阿托伐他汀(8毫克/千克/天)和胡椒碱(10毫克/千克/天);第六组给予胡椒碱(10毫克/千克/天)和非诺贝特(20毫克/千克/天)。第七组给予非诺贝特(20毫克/千克体重/天)和阿托伐他汀(8毫克/千克/天)。处死后,通过酶联免疫吸附测定法(ELISA)评估血清和睾丸中的胆固醇及睾酮水平,使用流式细胞术分析活性氧(ROS)的生成,测定丙二醛(MDA)、超氧化物歧化酶(SOD)和过氧化氢酶的含量。还进行了组织学、精子参数分析和生精评估。阿托伐他汀和胡椒碱的治疗显示出生殖毒性。非诺贝特与阿托伐他汀和胡椒碱联合治疗显示出保护作用。总之,阿托伐他汀和胡椒碱影响生殖潜能,而非诺贝特可能对阿托伐他汀和胡椒碱诱导的生殖毒性具有保护功效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/69aef48bacf0/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/db5d715f4b3a/ga1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/20712905a1af/gr2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/3c2457e894e6/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/3e63342d5603/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/f28bcdb02056/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/69aef48bacf0/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/db5d715f4b3a/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/111ee7f4f6ae/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/20712905a1af/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/9f1ca2f3eacd/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/c46ad6e1bace/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/3c2457e894e6/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/3e63342d5603/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/f28bcdb02056/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dfc/11699439/69aef48bacf0/gr8.jpg

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Fenofibrate and Diosmetin in a rat model of testicular toxicity: New insight on their protective mechanism through PPAR-α/NRF-2/HO-1 signaling pathway.
非诺贝特和地奥司明在睾丸毒性大鼠模型中的作用:通过 PPAR-α/NRF-2/HO-1 信号通路探讨其保护机制的新见解。
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Fenofibrate reduces cisplatin-induced apoptosis by inhibiting the p53/Puma/Caspase-9 pathway and the MAPK/Caspase-8 pathway rather than by promoting autophagy in murine renal proximal tubular cells.非诺贝特通过抑制p53/Puma/半胱天冬酶-9途径和丝裂原活化蛋白激酶/半胱天冬酶-8途径,而非通过促进小鼠肾近端小管细胞自噬,来减少顺铂诱导的细胞凋亡。
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