Melatonin-loaded nanoparticles reduce cisplatin-induced oxidative stress and lymphopenia: An experimental study in rats.

Abstract

This study aims to investigate the protective mechanisms of melatonin (Mel) and melatonin-loaded chitosan nanoparticles (ChitMelNPs) against cisplatin (CP)-induced oxidative stress and lymphopenia in rats. CP is a widely used chemotherapeutic drug known for its effectiveness in cancer treatment but associated with significant toxicities, particularly oxidative stress and hematological damage. Melatonin is noted for its ability to reduce inflammation and oxidative stress across various tissues. 40 male Wistar rats were divided into five groups: Control, Cisplatin (12 mg/kg), Melatonin (10 mg/kg), Melatonin-loaded chitosan nanoparticles (10 mg/kg), and Chitosan nanoparticles (10 mg/kg). They were gavaged for 15 days, received cisplatin (12 mg/kg, IP) on day sixteen, and were sacrificed after 48 h to obtain blood samples. Toxicity was assessed using hematological parameters, MDA, and TAC levels. Our findings showed that cisplatin induced decreases in body weight, WBC count, and TAC level, and increases in MDA levels (p < 0.001, p < 0.01, p < 0.05, and p < 0.001, respectively). Pretreatment with ChitMelNPs significantly reduced weight loss (-3.86 ± 0.98%) and lymphopenia (45.38 ± 14.98%) rather than CP group (-10 ± 1.37% and 13.67 ± 2.42% respectively). These ChitMelNPs improved TAC (208.5 ± 29.46 μmol/L) and reduced oxidative stress indicators, with a significant difference in CP group TAC levels (151.3 ± 28.47 μmol/L). They demonstrated increased antioxidant efficacy, indicating their potential to improve treatment outcomes. In conclusion, our research highlights the protective effects of Mel against cisplatin-induced toxicity, particularly in its nanoparticle form. As a treatment, ChitMelNPscan mitigate cisplatin-induced side effects.