Nucleosides rich extract from Cordyceps cicadae alleviated cisplatin-induced neurotoxicity in rats: A behavioral, biochemical and histopathological study

Abstract

This work explored the protective effects of nucleosides rich extract from C. cicadae (CCNE) against cisplatin-induced neurotoxicity. The rats were divided into four groups: normal control (NCA), cisplatin control (CCA), CCNE-L + cisplatin (CCNE-L) and CCNE-H + cisplatin (CCNE-H). The rats in CCNE-L and CCNE-H were orally administered with 100 and 400 mg/kg of CCNE, respectively for five weeks, while the rats in CCA, CCNE-L and CCNE-H groups received intraperitoneal injection of 2.5 mg/kg cisplatin once a week for four weeks starting from the second week of CCNE treatment. After the final treatment, the rats were subjected to behavioural task including Morris water maze test (MWMT), Y maze test, forced swimming (FST), open field test (OFT), rotarod test as well as heat and mechanical hyperalgesia test. Thereafter, the animals were sacrificed and oxidative stress biomarkers, inflammatory mediators and acetylcholinesterase activities were measured in the brain. The histopathological assessment of the brain issues was also performed using H&E staining. The results indicated that CCNE significantly ameliorative cisplatin induced learning and memory impairment (MWMT and Y maze test), depressive behaviours (FST and OFT), motor coordination as well as thermal (hot plate and tail withdrawal test) and mechanical hyperalgesia (von Frey filament test). Furthermore, CCNE decreased acetylcholinesterase level, proinflammatory cytokines levels and lipid peroxidation, with concomitant increase in antioxidant enzymes profiles in the brain tissues of cisplatin treated rats. Additionally, CCNE treatment alleviated histopathological alterations in the brain tissues caused by cisplatin treatment. These results suggested that CCNE ameliorated memory impairment deficits, neuropathy, increased oxidative stress, inflammation in cisplatin treated rats through the inhibition of oxidative stress and inflammation.