Long-term treatment with paracetamol induces cell death in cerebral cortex of rat brain

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Tipthanan Chotipinit
Weera Supronsinchai
Laddawan La-lert
Wilawan Ji-au
Preecha Reuangwechvorachai
Supang Maneesri le Grand


Background : Paracetamol (APAP) is the most widely used for treatment of pain and fever. In the last decade, several studies have demonstrated the effect of the drug in several systems including the nervous system. However, the effect is still controversial.

Objective : The present study aimed to investigate the effects of APAP for shortterm (0 and 5 days) and long-term (15 and 30 days) treatment on cell death in rat’s cerebral cortex

Methods : In this study, adult male Wistar rats were divided into two groups: control and APAP-treated groups. In the APAP-treated group, the animals were singly intraperitoneally injected with APAP at the dose of 200 mg/kg in
0 - day. In the APAP-treated group and the once daily injection at the same dose was performed in 5, 15 and 30 days APAP-treated group, respectively. After completion of the treatment, all rats were humanely killed, and the fresh specimens were collected to determine the expression of caspase-3. While the 4% paraformaldehyde fixed samples were collected for Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and immunohistochemical study.

Results : The results obtained from this study demonstrated that short-term treatment (0 and 5 days) with APAP had no effect on the caspase-3 expression and TUNEL-immunoreactive cells in the cerebral cortex. However, the results demonstrated that the expression of caspase-3 and the TUNEL-immunoreactive cells in the long-term APAP-treated groups were significantly greater than those in the control.

Conclusion : Based on these results, it can be suggested that short-term APAP treatment had no effect on the neurons in the cerebral cortex. However, long-term treatment with the drug can induce an increment of caspase-3
expression and neuronal cell death in this brain region.

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