Lipid peroxidation level and histological changes in rat liver after the cisplatin and dexamethasone separate and combined action

Abstract

Cisplatin is known to exhibit pro-oxidative properties, which are responsible for various toxicities caused by this drug, including hepatotoxicity. Dexamethasone, which is known as anti-inflammatory and immunomodulatory drug, is used with cisplatin to mitigate its side effects. However, dexamethasone, like other glucocorticoids, can induce oxidative stress and lipid peroxidation processes. In addition, it is known that dexamethasone causes liver damage and hepatotoxicity.
The aim of this study was to clarify how dexamethasone, having a similar effect to cisplatin, alleviates the side effects caused by this antitumor drug.
Our studies have shown that cisplatin and dexamethasone increase the formation of lipid peroxidation products conjugated dienes and trienes of rat’s liver to varying degrees extent in the case of separate and combined injection. In addition, cisplatin and dexamethasone were shown to increase the amount of lipid peroxidation marker malondialdehyde (MDA), in the rat liver tissue homogenate after separate and combined administration. These changes, as well as a decrease in the activity of the antioxidant enzyme catalase, confirm the pro-oxidative nature of cisplatin and dexamethasone. Moreover, the histopathological studies also testify to their hepatotoxic effect.
However, contrary to the expected synergistic enhancement of both lipid peroxidation processes, and histological changes, a reduction in cisplatin effect by dexamethasone was observed.
Thus, it is hypothesized that this “deterrent” effect of dexamethasone, combined with its anti-inflammatory and immunomodulatory properties, allows mitigating the side effects of cisplatin.