A possible role to nitric oxide in the anti-inflammatory effects of amitriptyline.
Antidepressants are reported to display anti-inflammatory effects. Nitric oxide (NO), in turn, has a key role in inflammation. The objective of the present study was to evaluate the effect of amitriptyline co-administered with L-NAME (a NO synthase inhibitor) on certain parameters of acute inflammatory response in rats, as a form to investigate a possible participation of NO in the anti-inflammatory effects of amitriptyline. For this, two animal models were used: carrageenan-induced paw edema and acute peritonitis. In the last one, peritoneal exudate, adhesion molecules expression by peripheral blood leukocytes and serum cytokines levels were evaluated. In a noninflammatory condition, serum levels of nitrates were determined. L-NAME induced a potentiation of the anti-inflammatory effects of amitriptyline (p < 0.05) in the paw edema model; however, these effects were not abrogated when L-NAME was substituted by L-arginine administration. A decrease in both leukocyte concentration and total number of cells in the peritoneal exudate and a reduction in the total serum levels of nitrates were observed with co-administration of L-NAME and amitriptyline (p < 0.05). No significant differences among groups were found concerning the expression of adhesion molecules by peripheral blood leukocytes (p > 0.05). There was a significant decrease on IL-1β and TNF-α serum levels in the experimental groups when compared to the control animals. Together the present results and the literature suggest that the anti-inflammatory effects of amitriptyline may be due to a decrease in NO production. A decrease in IL-1β/TNF-α serum levels may also be implicated in the results observed.
Department of Pathology, São Paulo University, Av. Prof. Dr. Orlando Marques de Paiva, Cidade Universitária, São Paulo, Brazil.
Luciana
L
Vismari
Glaucie J
GJ
Alves
Marcelo N
MN
Muscará
João
J
Palermo-Neto
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004487:Edema / Q000097:blood / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood*; D010538:Peritonitis / Q000097:blood / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012871:Skin Diseases / Q000097:blood / Q000188:drug therapy*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000929:Antidepressive Agents, Tricyclic; D016207:Cytokines; D004791:Enzyme Inhibitors; D000639:Amitriptyline; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester