Cancer Chemotherapeutic Drugs Induced Peripheral Neuropathy in Mice Effect of Flavone and its Monohydroxy Derivatives

Abstract

ABSTRACT newline newlineFlavonoids are group of compounds with established antioxidant and anti-inflammatory activity.Aim of the study is to investigate the effect of flavone and a few of its monohydroxy derivatives on CIPN induced by three important cancer chemotherapeutic drugs in mice. newlineFlavones and its monohydroxy derivatives were screened for their efficacy against the expression of certain neuropathic behavioral changes induced by paclitaxel, oxaliplatin and vincristine in mice for mechanical allodynia (von-Frey s hair aesthesiometer test, cold allodynia (Acetone bubble test) and thermal hyperalgesia (hot water tail immersion test). newlineProminent expression of the symptoms of CIPN evident in animals were attenuated by treatment with flavone and its derivatives to varying degrees in doses of 50, 100 and 200 mg/kg. The overall efficacy of 5-hydroxy flavone and#8805; 6-hydroxy flavone gtFlavone gt7-hydroxy flavone against CIPN in mice indicated structure activity relationship newlineNeuronal mechanisms involved in the action of flavone derivatives on paclitaxel induced CIPN in mice indicated the possible involvement of opioid, GABAergic, K+ATP channel, serotonergic and adrenergic systems. The degenerative changes in sciatic nerve resulting from paclitaxel administration were reversed to a major extent by flavones. newlineThe results of the present study revealed the protective effect of flavone and its monohydroxy derivatives against CIPN induced by three most commonly used cancer chemotherapeutic drugs. Different neuronal mechanisms involved in the protective effect of flavone derivatives have been identified. It was also established that structural changes in sciatic nerve resulting from paclitaxel administration in mice were attenuated by the investigated flavones. newlineThus, a new group of chemical scaffold flavones have been explored as a potential source of drug candidates in the treatment of CIPN.