Pattern differences between newborn and adult rats in cisplatin-induced hepatorenal toxicity

Abstract

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.