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Pattern differences between newborn and adult rats in cisplatin-induced hepatorenal toxicity
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2018-08-17 , DOI: 10.1016/j.cbi.2018.08.011
Bruna Cruz Weber Fulco , Juliano Ten Kathen Jung , Pietro Maria Chagas , Caroline Brandão Quines , Cristina Wayne Nogueira , Gilson Rogério Zeni

Although cisplatin (CIS) has been associated with serious adverse effects, such as hepatotoxicity and nephrotoxicity in adult rats, there is few reports on its use in newborn rats. The aim of this study was to evaluate acute toxic effects of CIS in newborn rats. Adult and newborn Wistar rats received CIS by the i. p. route, at the dose of 5 or 10 mg/kg. After 24 h of treatment, blood, kidney, and liver were excised from the animals and parameters of renal and hepatic functions, oxidative stress markers were determined. Acute administration of CIS caused an increase of AST activity and urea levels, suggesting hepatorenal toxicity in newborn and adult rats. However, the pattern and intensity of damage was different between ages and tissues. Newborn rats showed more pronouncedly oxidative stress damage, characterized by an increase in reactive species and protein carbonyl levels, lower NPSH content and highest inhibition in δ-ALA-D and CAT activities. Besides that, it was observed a faster molecular response in protein levels involved with apoptosis and oxidative stress response; whereas in the beginning the damage was less severe in the kidney than in the liver of adult rats. Thus, the present study shows that there are body response differences between adult and newborn rats to CIS acute exposure being that newborn rats are more susceptible than adults.



中文翻译:

新生大鼠和成年大鼠在顺铂诱导的肝肾毒性中的模式差异

尽管顺铂(CIS)与成年大鼠的肝毒性和肾毒性等严重不良反应有关,但有关在新生大鼠中使用顺铂的报道很少。这项研究的目的是评估CIS对新生大鼠的急性毒性作用。成年和新生Wistar大鼠通过ip途径接受CIS,剂量为5或10 mg / kg。治疗24小时后,从动物中切出血液,肾脏和肝脏,并测定肾和肝功能参数,确定氧化应激标志物。CIS的急性给药引起AST活性和尿素水平增加,提示新生大鼠和成年大鼠的肝肾毒性。但是,损伤的方式和强度在年龄和组织之间是不同的。新生大鼠表现出更明显的氧化应激损伤,其特点是反应物种和蛋白质羰基水平增加,NPSH含量降低,δ-ALA-D和CAT活性得到最大抑制。除此之外,还观察到与凋亡和氧化应激反应有关的蛋白质水平具有更快的分子反应。刚开始时,成年大鼠的肾脏损害不如肝脏严重。因此,本研究表明,成年和新生大鼠对CIS急性暴露的身体反应存在差异,因为新生大鼠比成年大鼠更易感。刚开始时,成年大鼠的肾脏损害不如肝脏严重。因此,本研究表明,成年和新生大鼠对CIS急性暴露的身体反应存在差异,因为新生大鼠比成年大鼠更易感。刚开始时,成年大鼠的肾脏损害不如肝脏严重。因此,本研究表明,成年和新生大鼠对CIS急性暴露的身体反应存在差异,因为新生大鼠比成年大鼠更易感。

更新日期:2018-08-17
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