The neuroprotective and cognitive effects of pirfenidone in a streptozotocin (STZ)-induced Alzheimer's disease model.

AIM: Alzheimer's disease (AD) is a neurodegenerative condition marked by cognitive deficits, including impairments in memory and orientation. Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) is a compound with demonstrated antifibrotic, anti-inflammatory, and antioxidant properties, primarily by suppressing various cytokines and mediators. This study investigates the effects of pirfenidone on hippocampal morphology, learning, memory, and inflammation in a Streptozotocin (STZ)-induced AD model. METHODS: 28 adult male Wistar albino rats were divided into four groups (n=7): Group 1, control group; Group 2, ICV-SF group; Group 3, ICV-STZ group; and Group 4, ICV-STZ + Pirfenidone (325 mg/kg, i.p) group. The AD model was created by administering STZ (3 mg/kg) intracerebroventricularly (ICV). The ICV-STZ + Pirfenidone group received pirfenidone (325 mg/kg) intraperitoneally for 15 days. Cognitive performance was assessed with the passive avoidance test (PAL). The neuron count in the right hippocampus and TNF-α, IL-6, and NF-κB levels in the left hippocampus and blood samples were measured. RESULTS: The ICV-STZ group showed decreased PAL latency, increased TNF-α, IL-6, and NF-κB levels, and a reduction in hippocampal neuron counts. Pirfenidone treatment significantly reduced IL-6 levels. It also tended to decrease TNF-α levels and modulate NF-κB expression; however, these changes did not reach statistical significance. CONCLUSION: Pirfenidone shows neuroprotective and cognitive benefits in an AD model, suggesting its potential as a complementary treatment for cognitive impairment and neurodegenerative diseases.