Purpose: Streptozotocin (STZ) is a naturally occurring chemical that, when injected intracerebroventricularly (ICV-STZ), is known to induce cognitive and memory deficits. Decreased the levels of antioxidant indexes including GSH is considered to be a major outcome of oxidative damage induced by ICV-STZ. N-Acetylcysteine (NAC), a derivative of the amino acid L-cysteine, is widely recognized as the most extensively utilized antioxidant in both experimental and clinical studies. It exhibits neuroprotective properties and functions as a radical scavenger by replenishing GSH. The study intends to investigate whether N-acetylcysteine administration can mitigate the negative effects of streptozotocin, such as memory impairment and oxidative stress, by evaluating its potential neuroprotective and antioxidant properties. Methods and Materials: In this study, 30 male Wistar rats weighing approximately 180-250 gr were obtained from the Pasteur Institute in Amol, Iran. The animals were divided into three control groups (distilled water orally), Saline (STZ) group (stereotaxic injection of 3 mg/kg of STZ and Saline orally) and NAC group (stereotaxic injection of 3 mg/kg of STZ and 50 mg/kg of NAC orally). After 21 days of treatment, passive avoidance memory test and GSH content measurement was performed. Results: The results of the research show that the Saline (STZ) group had significantly (P < 0.001) less delay to enter the dark area and spent more time in the dark area than the control group. Also, NAC at a dose of 50 mg/kg showed a similar result in this indexes compared to the control group. In addition, treatment with NAC showed a significant increase in the delay of entering the dark area (P < 0.01) and a significant decrease in the time spent in the dark area (P < 0.001) compared to the Saline (STZ) group. Statistical analysis indicated that the Saline (STZ) group significantly decreased (P < 0.01) the hippocampal GSH level compared with control group. NAC group significantly increased (P < 0.05) the hippocampal GSH level compared with Saline (STZ) group. Conclusion: The findings of the present study demonstrate that the administration of NAC at a dosage of 50 mg/kg leads to a significant improvement in memory decline. Also counteracts the oxidative stress by increasing the GSH content in an animal model of Alzheimer's disease.
