Background: Zinc oxide Nanoparticles (NPs) present irreversible effects on the nervous system, memory, and learning. Objective: The current study aimed to investigate the effects of pentoxifylline on memory impairments, CA1 hippocampal pyramidal cells, and blood serum antioxidant enzymes in male rats treated with zinc oxide NPs. Methods: Male Wistar rats were divided into the control, zinc oxide NPs (1.25 mg/kg), pentoxifylline (50 mg/kg), and pentoxifylline with zinc oxide NPs groups. In all study groups, saline, zinc oxide NPs, and pentoxifylline were intraperitoneally injected 30 minutes before training. In the co-treatment group, pentoxifylline was injected one hour before injecting Zno NPs. After performing the behavioral test, the tested animals’ brains were fixed and the number of healthy neurons in the CA1 region of the hippocampus was counted. In all research groups, malondialdehyde levels, total antioxidant power, superoxide dismutase levels, and glutathione peroxidase in blood serum were measured. Results: Zinc oxide nanoparticles decreased memory and the number of healthy neurons in the CA1 region of the hippocampus and increased oxidative stress in blood serum, compared to the controls. In the co-treatment group, using pentoxifylline improved the above-mentioned factors and reached the level of the control group. Pentoxifylline alone presented no significant effect on the aforementioned characteristics, compared to the control group. Conclusion: ZnO NPs may decrease memory retrieval and cause cell death in the pyramidal neurons of the CA1 region of the hippocampus by increasing oxidative stress. Pentoxifylline, as a potent antioxidant, can prevent the harmful effects of ZnO NPs.
