Tempol effect on oxidative and mitochondrial markers in preclinical models for prostate cancer.

IF 2.2 4区 医学 Q3 TOXICOLOGY Toxicology Research Pub Date : 2024-04-01 DOI:10.1093/toxres/tfae056
I. Rossetto, F. Santos, Heloina Nathalliê Mariano da Silva, Elaine Minatel, Mariana Mesquitta, Marcos José Salvador, F. Montico, V. Cagnon
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Abstract

Background Tempol is a redox-cycling nitroxide considered a potent antioxidant. The present study investigated the tempol effects on oxidative stress and mitochondrial markers on prostate cancer (PCa). Methods PC-3 and LnCaP cells were exposed to tempol. Cell viability test, western blot and Amplex Red analyses were performed. In vivo, five experimental groups evaluated tempol effects in the early (CT12 and TPL12 groups) and late stages (CT20, TPL20-I, and TLP20-II) of PCa development. The TPL groups were treated with 50 or 100 mg/kg tempol doses. Control groups received water as the vehicle. The ventral lobe of the prostate and the blood were collected and submitted to western blotting or enzymatic activity analyses. Results In vitro, tempol decreased cell viability and differentially altered the H2O2 content for PC-3 and LNCaP. Tempol increased SOD2 levels in both cell lines and did not alter Catalase protein levels. In vivo, tempol increased SOD2 levels in the early stage and did not change Catalase levels in the different PCa stages. Systemically, tempol decreased SOD2 levels in the late-stage and improved redox status in the early and late stages, which was confirmed by reduced LDH in tempol groups. Alterations on energetic metabolism and oxidative phosphorylation were observed in TRAMP model. Conclusion Tempol can be considered a beneficial therapy for PCa treatment considering its antioxidant and low toxicity properties, however the PCa progression must be evaluated to get successful therapy.
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坦泊对前列腺癌临床前模型中氧化和线粒体标记物的影响
背景Tempol是一种氧化还原循环亚硝基化合物,被认为是一种有效的抗氧化剂。本研究探讨了 tempol 对前列腺癌(PCa)氧化应激和线粒体标志物的影响。方法 PC-3 和 LnCaP 细胞暴露于 tempol,进行细胞活力测试、Western 印迹和 Amplex Red 分析。在体内,五个实验组分别评估了 tempol 对 PCa 早期(CT12 组和 TPL12 组)和晚期(CT20、TPL20-I 和 TLP20-II)的影响。TPL组接受50或100毫克/千克剂量的tempol治疗。对照组以水为载体。收集前列腺腹叶和血液并进行 Western 印迹或酶活性分析。结果体外试验中,tempol 降低了 PC-3 和 LNCaP 的细胞活力,并不同程度地改变了 H2O2 的含量。Tempol提高了这两种细胞系的SOD2水平,但没有改变过氧化氢酶蛋白水平。在体内,tempol 增加了早期 PCa 中的 SOD2 水平,但没有改变不同 PCa 期的过氧化氢酶水平。在体内,tempol可降低晚期PCa细胞的SOD2水平,改善早期和晚期PCa细胞的氧化还原状态,tempol组LDH的降低证实了这一点。TRAMP模型中观察到了能量代谢和氧化磷酸化的改变。
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来源期刊
Toxicology Research
Toxicology Research TOXICOLOGY-
CiteScore
3.60
自引率
0.00%
发文量
82
期刊介绍: A multi-disciplinary journal covering the best research in both fundamental and applied aspects of toxicology
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