Abstract
Background: Growing evidences indicate that endogenous oxidants and antioxidant defense interact in a vicious cycle, which plays a critical role in the pathogenesis of cognitive dysfunction. In this study, we examined the effect of N-acetyl cysteine (NAC) against the intracerebroventricular infusion of streptozotocin (ICV STZ)-induced cognitive impairment and mitochondrial oxidative damage in rats.
Methods: Male adult Wistar rats were injected with STZ (3 mg/kg) bilaterally through ICV. NAC (50 and 100 mg/kg) was administered for 3 weeks post-surgery. The rats were sacrificed on the 21st day following the last behavioral test, and cytoplasmic fractions of the hippocampus and cortex were prepared for the quantification of acetylcholinesterase, oxidative stress parameter, mitochondrial enzymes, inflammatory mediators and caspase-3 activity.
Results: ICV STZ resulted in poor retention of memory in Morris water maze. It also increased the mito-oxidative damage and tumor necrosis factor-α, interleukin 6 and caspase-3 levels in the hippocampus and cortex compared to sham animals. NAC significantly improved memory retention and attenuated oxidative damage parameters, inflammatory markers in STZ-treated rats.
Conclusions: The results of the present study strongly indicate the effectiveness of NAC in preventing cognitive impairment as well as mito-oxidative stress and may be considered as a potential agent in the management of cognitive-related disorders.
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