Corresponding author: Dr. Supang Maneesri-le Grand Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand Telephone: +66 2 256 4000 ext. 3519 Facsimile: +66 2 252 7854
E-mail: le firstname.lastname@example.org
Received : 20 August 2013; Accepted : 8 October 2013
Background: Paracetamol is one of the most popular drugs used for treatment of pain and headaches. Recent evidences have indicated that long term treatment with this drug can induce the neurotoxic effect in the brain including in the hippocampal neurons, however the mechanism underlying its neurotoxic effect is still unclear. The present study aimed to investigate the effect of long term treatment with paracetamol on the expression of pro-inflammatory cytokines IL-1a and TNF-a in the hippocampus using immunohistochemistry.
Methods: Male Wistar rats (250-300 g) were divided into control and paracetamol treated groups. A single dose for 0 day and a single daily paracetamol (200 mg/kg BW, intraperitoneally) treatment for a period of 5, 15, and 30 days was injected into the paracetamol-treated group (n=5, each) whereas the control group received vehicle injections at the same volume. After finishing the treatment, all rats were humanely killed by injection of a sodium pentobarbital overdose (i.p.). The expression of pro-inflammatory cytokines (IL-1a/TNF-a) in hippocampus was studied by immunohistochemical techniques.
Results: The results showed that short-term exposure with paracetamol (0 and 5 days) had no effect on the expression of IL-1a. However, long-term paracetamol treatment for 15 and 30 days induced a significant increase in the expression of IL-1a in the hippocampus compared with those observed in the control group. The expression of TNF-a showed an overall similar pattern with the immunohistochemical study of IL-1a. Interestingly, when comparing the level of pro-inflammatory cytokine expression in the paracetamol treated group between15 and 30 days of treatment, the expression of IL-1a and TNF-a in the 30 days paracetamol treated group was higher.
Conclusions: The present study demonstrates that long-term exposure with paracetamol induces an increase in the expression of pro-inflammatory cytokines (both IL-1a and TNF-a) in hippocampus. Since the increase of pro-inflammatory cytokines is associated with the degeneration of hippocampal neurons, with our present results it could be concluded that the abnormality of learning and memory in patients with long term exposure of paracetamol possibly exists.