Abstract
Backgrounds: Several
studies have recently revealed that cognitive function can be affected by
paracetamol (APAP) treatment. However, the exact impact of this drug treatment
on learning and memory has not been clarified. This study aimed to investigate
the effect of APAP treatment on the alteration of synapses and oxidative stress
in the rat frontal cortex and hippocampus.
Methods: APAP at a dose of 200 mg/kg bw was fed to
adult male Wistar rats through either acute (0 days, n = 10), sub-chronic (15
days, n = 10) or chronic (30 days, n = 10) treatment regimens. The synaptic
ultrastructure and proteins, synaptophysin (SYP) and postsynaptic density-95
(PSD-95), were monitored. The amount of protein carbonyl oxidation (PCO) and
glutathione (GSH) levels were examined. Our results demonstrated that acute
treatment with APAP had no effect on the synapses and oxidative stress.
However, the synapses obtained from rats with subchronic APAP treatment showed
a marked shortening of active zones and widening of the synaptic cleft. Decrement
of SYP and PSD-95 proteins were demonstrated in these rats as well. With 30-day
APAP treatment, the alteration of the synaptic ultrastructure and proteins was
more evident. Moreover, the depletion of GSH and the elevation of PCO levels
were demonstrated in the rats treated chronically with APAP.
Conclusions: These results suggest that chronic APAP treatment can induce synaptic degeneration in the hippocampus and frontal cortex. The increase in oxidative stress in these brain areas may be due to the deleterious effect of this drug.