通过抑制氧化损伤、炎症和凋亡,黄芩素能够减轻紫杉醇诱导的大鼠肝肾毒性。
Chrysin attenuates paclitaxel-induced hepatorenal toxicity in rats by suppressing oxidative damage, inflammation, and apoptosis.
发表日期:2023 Sep 14
作者:
Selim Çomaklı, Selçuk Özdemir, Meryem Güloğlu
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
紫杉醇(Pax)是紫杉醇家族中的一种化疗药物,用于治疗人类癌症,包括卵巢癌、乳腺癌和非小细胞肺癌。染料木素(CR)具有抗氧化、抗炎、抗凋亡、抗糖尿病和抗致癌性质,以及肝保护和肾保护活性。本研究评估了CR对Pax诱导的肝肾毒性中炎症、凋亡、抗氧化水平、氧化性DNA损伤和组织病理学的保护作用。将三十五只雄性Sprague-Dawley大鼠分为五组(n=7),第一组(正常对照组),第二组(CR单独给予剂量为50mg/kg),第三组(Pax给予剂量为2mg/kg),第四组(Pax+CR 25组),和第五组(Pax+CR 50组)。采用RT-PCR从石蜡切片中评估了凋亡(Bax和Bcl-2)和抗氧化基因(SOD1、CAT、GPx3和GST)的表达。还通过免疫组织化学检查确定了Caspase 3、KIM-1、NF-kB、COX-2和8-OHdG的表达。
结果显示,Pax暴露导致大鼠肝肾损伤,表现为Caspase 3、Bax、KIM-1、NF-kB、COX-2和8-OHdG的显著升高。然而,Bcl-2、SOD1、CAT、GPx3和GST基因的表达明显下调。相反,联合给予CR的大鼠显示了更好的基因表达、组织结构和免疫组织化学染色结果。
因此,CR表现出减少氧化性DNA损伤、具有抗凋亡和抗炎性能,并减轻Pax诱导的肝肾毒性的毒性作用的能力。
版权所有 ©2023。由Elsevier Inc.发表。
Paclitaxel (Pax) is a chemotherapeutic drug from the taxane family that is used in the treatment of human cancer, including ovarian, breast, and non-small cell lung carcinoma. Chrysin (CR) has antioxidant, anti-inflammatory, anti-apoptotic, anti-diabetic, and anti-carcinogenic properties, as well as hepatoprotective and renoprotective activities. In the present study, we evaluated the protective effect of CR against Pax-induced hepatorenal toxicity on inflammation, apoptosis, antioxidant levels, oxidative DNA damage, and histopathology in rats.Thirty-five male Sprague-Dawley rats were divided into five groups (n = 7): Group I (normal control), Group II (CR alone at a dose of 50 mg/kg), Group III (Pax at a dose of 2 mg/kg), Group IV (Pax+CR 25), and Group V (Pax+CR 50). The expressions of apoptotic (Bax and Bcl-2) and antioxidant genes (SOD1, CAT, GPx3, and GST) were evaluated using RT-PCR from paraffin sections. Caspase 3, KIM-1, NF-kB, COX-2, and 8-OHdG were also determined by immunohistochemical examination.The results revealed that Pax exposure caused hepatic and renal damage in rats, which was indicated by a significant elevation of caspase 3, Bax, KIM-1, NF-kB, COX-2, and 8-OHdG. However, there was a marked downregulation in the expressions of the Bcl-2, SOD1, CAT, GPx3, and GST genes. In contrast, rats given CR in combination showed better gene expression, histological structure, and immunohistochemical staining results.Consequently, CR exhibited the ability to reduce oxidative DNA damage, exert anti-apoptotic and anti-inflammatory properties, and mitigate the toxic effects of Pax-induced hepatorenal toxicity.Copyright © 2023. Published by Elsevier Inc.