Ameliorative effect of allopurinol on cisplatin-induced memory impairment in male Wistar rat

Document Type : Research Paper

Authors

1 Cellular and Molecular Research Center, Sbzevar University of Medical Sience, Sabzevar, Iran. Department of Physiology and Pharmacology, Sbzevar University of Medical Sience, Sabzevar, Iran.

2 Sabzevar university of medical science

3 Cellular and Molecular Research Center, Department of Physiology and Pharmacology, Sabzevar University of Medical Science, Sabzevar, Iran.

4 Department of Nutrition & BioChemistry, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

10.22034/ijps.2022.537410.1891

Abstract

Neurotoxicity is an adverse effect of chemotherapy drugs on the central nervous system. Many studies have
demonstrated that xanthine oxidase inhibitors prevent the formation of reactive oxygen species (ROS). The present
study aimed to investigate the effects of allopurinol as an oxidase inhibitor on the learning and memory impairment
induced by cisplatin. This study was conducted on 40 male Wistar rats, which were randomly divided into five
groups, as follows: 1) control injected with saline (1 ml/kg/i.p); 2) cisplatin (5 mg/kg/once a week; i.p.); 3) allopurinol
(ALP; 50 mg/kg/once a week; P.O.); 4) Cis+ALP 50 (cisplatin 5 mg/kg/i.p and allopurinol50 mg/kg/once a week;
P.O.) and 5) Cis+ALP 100 (cisplatin 5 mg/kg/i.p and allopurinol100 mg/kg/once a week; P.O.). Drugs were
administered for five weeks in all groups. The interval between administrations of drugs were half an hour. Morris
water maze (MWM) was used to evaluate the memory and learning of the animals. The tissue brain concentrations
of malondialdehyde (MDA), thiol, and superoxide dismutase (SOD) were measured using biochemical tests.
According to the results, the cisplatin group had longer escape latency and shorter time spent and traveled pathway
in the target quadrant compared to the control group. On the other hand, allopurinol treatment significantly reversed
the results of the spatial memory test. The biochemical data indicated that cisplatin increased MDA concentration
but decreased thiol and SOD activity compared to the control group. Administration of allopurinol decreased the
MDA level but increased the thiol levels in the cortex and hippocampus tissues. Therefore, it was concluded that
allopurinol could improve cisplatin-induced memory impairment by affecting the oxidative status of the brain tissue.

Keywords

Iranian Journal of Pharmaceutical Sciences
Volume 18, Issue 1
January 2022
Pages 35-45

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