Beta-carotene ameliorates diabetic nephropathy in rats: involvement of AMPK/SIRT1/autophagy pathway.

IF 2.9 4区 医学 Q3 IMMUNOLOGY
Salma A El-Marasy, Hadir Farouk, Marwa S Khattab, Passant E Moustafa
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引用次数: 0

Abstract

Objective: This study aimed to demonstrate the protective effect of beta-carotene against STZ-induced DN in rats and explore the possible underlying mechanisms that may have mediated such condition.

Material and methods: Wistar rats were allocated into four groups. Normal group received distilled water for 3 weeks. The other three groups were rendered diabetic by an intraperitoneal dose of STZ (50 mg/kg), 48 h later, group 2: received the vehicle and served as control, groups (3 &4) received orally beta-carotene in doses of 10 and 20 mg/kg, respectively for 3 weeks. Then serum and renal tissue were collected for biochemical, molecular, immunohistopathological, and histopathological examination.

Results: Beta-carotene ameliorated the reduction in body weight, reduced blood glucose, elevated serum insulin, reduced blood urea nitrogen, and serum creatinine levels. Beta-carotene elevated phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK)/AMPK, alleviated phosphorylated mammalian target of rapamycin (p-mTOR)/mTOR, reduced interleukin 1 beta (IL-1β), increased Beclin 1, LC3II/LC3I, and reduced p62 renal contents. Moreover, it elevated renal SIRT1 gene expression and reduced renal tumor necrosis factor-alpha (TNF-α) and caspase-3 protein expressions.

Conclusion: Beta-carotene exerted renoprotective effect against STZ-induced DN and histopathological alterations through alleviating hyperglycemia, attenuating inflammation, activating AMPK/SIRT1/autophagy pathway, and combating apoptosis.

β-胡萝卜素改善大鼠糖尿病肾病:AMPK/SIRT1/自噬途径的参与
研究目的本研究旨在证明β-胡萝卜素对STZ诱导的大鼠DN具有保护作用,并探讨可能导致这种情况的潜在机制:将 Wistar 大鼠分为四组。正常组接受蒸馏水治疗 3 周。其他三组在 48 小时后腹腔注射 STZ(50 毫克/千克)使大鼠患糖尿病,第 2 组接受载体作为对照,第 3 组和第 4 组分别口服剂量为 10 毫克/千克和 20 毫克/千克的 beta-胡萝卜素,连续 3 周。然后采集血清和肾组织进行生化、分子、免疫组织病理学和组织病理学检查:结果:β-胡萝卜素可改善体重下降、血糖降低、血清胰岛素升高、血尿素氮和血清肌酐水平降低的情况。β-胡萝卜素提高了磷酸化 5'单磷酸腺苷激活的蛋白激酶(p-AMPK)/AMPK,减轻了磷酸化哺乳动物雷帕霉素靶标(p-mTOR)/mTOR,降低了白细胞介素 1 beta(IL-1β),增加了 Beclin 1、LC3II/LC3I,降低了 p62 肾脏含量。此外,β-胡萝卜素还能提高肾脏SIRT1基因的表达,降低肾脏肿瘤坏死因子-α(TNF-α)和caspase-3蛋白的表达:结论:β-胡萝卜素通过缓解高血糖、减轻炎症反应、激活AMPK/SIRT1/自噬通路和抑制细胞凋亡,对STZ诱导的DN和组织病理学改变具有肾脏保护作用。
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来源期刊
CiteScore
5.40
自引率
0.00%
发文量
133
审稿时长
4-8 weeks
期刊介绍: The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).
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