Pioglitazone improves tamoxifen-induced renal injury in rat model through modulating oxidative stress, inflammation, and apoptosis signaling

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-09-29 DOI:10.1016/j.tice.2025.103154

Gellan Alaa Mohamed Kamel , Shaimaa Hussein

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引用次数: 0

Abstract

One prevalent chemotherapeutic medication used to treat breast cancer is tamoxifen (TAM), and several off-label uses. However, when used as an antineoplastic drug in clinical settings, it causes harmful cellular effects such as renal damage. The mechanisms underlying TAM-induced kidney injury primarily involve oxidative stress and inflammatory pathways. Pioglitazone (PIO), an agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ), is a medication primarily indicated for type 2 diabetes mellitus. Beyond its hypoglycemic actions, PIO exhibits potent anti-inflammatory and antioxidant effects, which have been documented in various tissues. Hence, this study investigates the potential protective effects of PIO on TAM-induced renal impairment, revealing their possible protective mechanisms. The rats were orally administered doses of PIO (10 mg/kg) and TAM (45 mg/kg) over ten days. Renal histopathological changes, kidney function, and biochemical examination are conducted. TAM raised serum creatinine and urea levels, leading to histopathological changes, renal oxidative stress, and elevated expression of NF-κB p65 and proinflammatory cytokines. Conversely, PIO treatment exerted a protective effect and attenuated TAM-induced nephrotoxicity. Significantly, malondialdehyde (MDA) and proinflammatory markers were reduced while enhancing renal antioxidant activity. Furthermore, renal Nrf2, HO-1, Bcl-2 expression while lowering NF-κB, KIM-1, Bax and caspase-3 levels. In conclusion, PIO demonstrated significant nephroprotective effects against TAM-induced renal damage by inhibiting apoptosis, reducing inflammation, and counteracting oxidative stress.

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吡格列酮通过调节氧化应激、炎症和细胞凋亡信号通路改善他莫昔芬诱导的大鼠肾损伤模型。

用于治疗乳腺癌的一种流行的化疗药物是他莫昔芬（TAM），以及一些未经核准的用途。然而，当临床上用作抗肿瘤药物时，它会引起有害的细胞效应，如肾损伤。tam诱导肾损伤的机制主要涉及氧化应激和炎症途径。吡格列酮（PIO）是一种过氧化物酶体增殖物激活受体γ (PPAR-γ)的激动剂，主要用于2型糖尿病。除了它的降糖作用，PIO还显示出有效的抗炎和抗氧化作用，这在各种组织中都有记载。因此，本研究探讨PIO对tam所致肾损害的潜在保护作用，揭示其可能的保护机制。大鼠连续10天口服PIO（10 mg/kg）和TAM（45 mg/kg）。进行肾脏组织病理改变、肾功能及生化检查。TAM升高血清肌酐和尿素水平，导致组织病理改变，肾脏氧化应激，NF-κB p65和促炎细胞因子表达升高。相反，PIO治疗发挥保护作用并减轻tam引起的肾毒性。显著降低丙二醛（MDA）和促炎标志物，增强肾脏抗氧化活性。此外，肾Nrf2、HO-1、Bcl-2表达降低NF-κB、KIM-1、Bax和caspase-3水平。综上所述，PIO通过抑制细胞凋亡、减少炎症和对抗氧化应激，对tam诱导的肾损伤具有显著的肾保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.