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奥利司他与二甲双胍联合使用可通过抑制雄性大鼠的肾脏氧化应激来改善肥胖诱导的肾损伤。

Orlistat and metformin combination ameliorates obesity-induced renal injury via suppressing renal oxidative stress in male rats.

作者信息

Alsolami Khadeejah, Hamza Reham Z

机构信息

Pharmacology and Toxicology Department, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

Biology Department, College of Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

出版信息

Toxicol Res (Camb). 2024 Aug 21;13(4):tfae135. doi: 10.1093/toxres/tfae135. eCollection 2024 Aug.

DOI:10.1093/toxres/tfae135
PMID:39175812
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11336066/
Abstract

BACKGROUND

Orlistat (ORS) and metformin (MEF) are robustly used as well-established clinical drugs for the treatment for both obesity and the consequences of diabetes mellitus. Additionally, no study has been conducted to explore the consequence of the combination of both ORS and MEF on the kidneys of rats with obesity-induced renal injury (OBS).

OBJECTIVES

Therefore, the objective of the current research was designed to explore the possible ameliorative effects of either ORS and/or MEF or their combination against obesity (OBS) induced experimental renal oxidative stress.

METHODS

Renal oxidative stress was investigated at redox histopathological and immunohistological points in the kidney tissues.

RESULTS

The levels of urea, uric acid, and creatinine increased with the obesity effect; in addition, the myeloperoxidase (MPO) and xanthine oxidase (XO) activators were elevated significantly with the induction of OBS. The levels of non-enzymatic antioxidants (glutathione and thiol) declined sharply in OBS rats as compared to the normal group.

CONCLUSION

The data displayed that the combination of both ORS and MEF declined the obesity effects significantly by reducing the level of peroxidation (MDA), and enhancement intracellular antioxidant enzymes. These biochemical findings were supported by histopathology, immunohistochemistry, and Masson-Trichrome evaluation, which showed minor morphological changes in the kidneys of rats.

摘要

背景

奥利司他(ORS)和二甲双胍(MEF)作为成熟的临床药物,被广泛用于治疗肥胖症和糖尿病的并发症。此外,尚未有研究探讨ORS和MEF联合使用对肥胖诱导的肾损伤(OBS)大鼠肾脏的影响。

目的

因此,本研究的目的是探讨ORS和/或MEF或它们的组合对肥胖(OBS)诱导的实验性肾氧化应激的可能改善作用。

方法

在肾脏组织的氧化还原组织病理学和免疫组织学层面研究肾氧化应激。

结果

尿素、尿酸和肌酐水平随肥胖效应而升高;此外,随着OBS的诱导,髓过氧化物酶(MPO)和黄嘌呤氧化酶(XO)激活剂显著升高。与正常组相比,OBS大鼠的非酶抗氧化剂(谷胱甘肽和硫醇)水平急剧下降。

结论

数据显示,ORS和MEF联合使用通过降低过氧化水平(MDA)和增强细胞内抗氧化酶,显著降低了肥胖效应。这些生化结果得到了组织病理学、免疫组织化学和Masson三色染色评估的支持,这些评估显示大鼠肾脏的形态变化较小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4fd/11336066/ce0a60a35201/tfae135ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4fd/11336066/ce0a60a35201/tfae135ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4fd/11336066/ce0a60a35201/tfae135ga1.jpg

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本文引用的文献

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Efficacy and safety of orlistat in male patients with overweight/obesity and hyperuricemia: results of a randomized, double-blind, placebo-controlled trial.奥利司他在超重/肥胖合并高尿酸血症男性患者中的疗效与安全性:一项随机、双盲、安慰剂对照试验的结果
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Impact of metformin on cardiovascular and kidney outcome based on kidney function status in type 2 diabetic patients: a multicentric, retrospective cohort study.
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Ameliorative effects of Orlistat and metformin either alone or in combination on liver functions, structure, immunoreactivity and antioxidant enzymes in experimentally induced obesity in male rats.奥利司他和二甲双胍单独或联合使用对雄性大鼠实验性诱导肥胖模型的肝功能、肝脏结构、免疫反应性及抗氧化酶的改善作用
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