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Evaluation of Toxic Effects of Novel Platinum (IV) Complexes in Female Rat Liver: Potential Protective Role of Resveratrol
Cell Biochemistry and Biophysics ( IF 1.8 ) Pub Date : 2020-10-22 , DOI: 10.1007/s12013-020-00953-y
Milica G Paunović 1 , Miloš M Matić 1 , Vesna D Stanković 2 , Marija D Milošević 1 , Verica V Jevtić 3 , Srećko R Trifunović 3 , Branka I Ognjanović 1
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The use of cisplatin in chemotherapy may provoke a deteriorating impact in many vital organs, suggesting the need for more selective derivatives and effective protective cotreatments. This study assesses the effects of three novel Pt(IV) complexes containing ethyl-, propyl- and butyl-esters of the ethylenediamine-N, N’-di-S, S- (2,2’-dibenzyl) acetic acid on liver injury markers, redox parameters, and cell morphology of female rat liver tissue in comparison to cisplatin. In addition, the study evaluates the possible protective effects of resveratrol as well. The rats were divided into ten groups and were administered intraperitoneally with a single dose of cisplatin (7.5 mg/kg) or Pt(IV) complexes (10 mg/kg) and/or resveratrol (25 mg/kg). All treatments caused changes in body weight, food intake, and liver/bw ratio. Acute treatment with novel complexes decreased the levels of TB and TP while elevated the activity of ALT, AST, GGT, ALP which subsequently indicated on the liver damage. All three complexes significantly reduced the levels of LPO, O2.−, NO2 and activity of CAT, while increasing the activity of SOD, GSH-Px, GR, GST, and level of GSH, implying that these compounds could provoke redox balance disruption in liver cells. Moreover, according to the histopathological observations, the novel Pt(IV) complexes exerted stronger hepatotoxicity than cisplatin. Possible protective effects of resveratrol were not detected and even combined with examined compounds it abolished the activity of the antioxidative system of the liver cells causing more intense toxicity. Further investigation is required to elucidate the effects of Pt-based drugs and resveratrol in the estradiol-rich environment of female rats as well their influence on male rats’ tissues.



中文翻译:

新型铂(IV)配合物对雌性大鼠肝脏的毒性作用评估:白藜芦醇的潜在保护作用

在化学疗法中使用顺铂可能在许多重要器官中引起恶化的影响,这表明需要更多的选择性衍生物和有效的保护性联合治疗。这项研究评估了三种新型的Pt(IV)配合物的效果,这些配合物包含乙二胺-N,N'--S,S的乙基,丙基和丁基酯-与顺铂相比,(2,2'-二苄基)乙酸对雌性大鼠肝组织的肝损伤标志物,氧化还原参数和细胞形态的影响。此外,该研究还评估了白藜芦醇的可能保护作用。将大鼠分为十组,并腹膜内给予单剂量的顺铂(7.5 mg / kg)或Pt(IV)复合物(10 mg / kg)和/或白藜芦醇(25 mg / kg)。所有治疗均引起体重,食物摄入量和肝/体重比的变化。新型复合物的急性治疗降低了TB和TP的水平,同时提高了ALT,AST,GGT,ALP的活性,这随后表明了对肝的损害。所有这三个复合显著降低LPO水平,O- 2 .-,NO 2 -CAT的活性,同时增加SOD,GSH-Px,GR,GST和GSH的活性,这暗示这些化合物可引起肝细胞氧化还原平衡的破坏。此外,根据组织病理学观察,新型Pt(IV)复合物比顺铂具有更强的肝毒性。没有检测到白藜芦醇的可能的保护作用,甚至与所检查的化合物组合使用时,它消除了肝细胞抗氧化系统的活性,引起了更强的毒性。需要进一步研究以阐明基于Pt的药物和白藜芦醇在雌性大鼠富含雌二醇的环境中的作用及其对雄性大鼠组织的影响。

更新日期:2020-10-30
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