Abstract
This study aimed at studying the potential neuroprotective effect of Rutin hydrate (RH) alone or in conjugation with α-tocopherol against cadmium chloride (CdCl2)-induced neurotoxicity and cognitive impairment in rats and to investigate the mechanisms of action. Rats intoxicated with CdCl2 were treated with the vehicle, RH, α-tocopherol or combined treatment were examined, and compared to control rats received vehicle or individual doses of either drug. Data confirmed that RH improves spatial memory function by increasing acetylcholine availability, boosting endogenous antioxidant potential, activating cell survival and inhibiting apoptotic pathways, an effect that is more effective when RH was conjugated with α-tocopherol. Mechanism of RH action includes activation of PP2A mediated inhibiting of ERK1/2 and JNK apoptotic pathways and inhibition of PTEN mediated activation of mTOR survival pathway. In conclusion, RH affords a potent neuroprotection against CdCl2-induced brain damage and memory dysfunction and co-administration of α-tocopherol enhances its activity.
Acknowledgements
Authors thank the technical staff of the animal house facilities at the College of Medicine at King Khalid University for their help in the management, taking care and feeding of the animals used in this study. In addition, the authors wish to thank the technical staff at the Department of Biochemistry, College of Medicine and those at the Department of physiology at the College of Medicine, in King Khalid University for their help in this study. The authors extend their appreciation to the deanship of scientific research at King Khalid University for funding this work through general research project under grant number (520).
Disclosure statement
No potential conflict of interest was reported by the authors.