Bothrops jararaca and Crotalus durissus terrificus venoms elicit distinct responses regarding to production of prostaglandins E2 and D2, and expression of cyclooxygenases.
Prostaglandins (PGs), synthesized by cyclooxygenases, play important roles in many pathophysiological processes including inflammation and hyperalgesia. In this study the profiles of PGE(2) and PGD(2) production secondary to injection of Bothrops jararaca venom (BjV), with inflammatory activity or Crotalus durissus terrificus venom (CdtV), with anti-inflammatory and antinociceptive properties, into mice were evaluated, and the ability of these venoms to induce expression of cyclooxygenases-1 (COX-1) and -2 (COX-2) was investigated. Intraperitoneal injection of BjV but not of CdtV induced the release and PGD(2) at 30 min and of PGE(2) from 3 up to 12 h after injection. Moreover, BjV up-regulated expression of COX-2 but not of the constitutive COX-1, suggesting that expressed COX-2 provides more substrate for synthesis of PGs by the respective terminal synthases, being the critical enzyme for PGs production in the late periods of BjV effect. In contrast, CdtV does not have any effect on constitutive COX-1 and do not induce expression of COX-2. Therefore, differences between BjV and CdtV in the ability to regulate PGs synthesis can account for their distinct effects with regard to inflammation. Moreover, inhibition of COX-2 by selective drugs may be of value to counteract the severe local inflammation induced by BjV in the victims.
Moreira
Vanessa
V
Laboratory of Pharmacology, Butantan Institute, Ave Vital Brazil, 1500, 05503-900 Sao Paulo, Brazil.
Zamuner
Stella Regina
SR
Wallace
John L
JL
Teixeira
Catarina de Fátima Pereira
Cde F
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D017837:Bothrops; D003435:Crotalid Venoms / Q000633:toxicity*; D017839:Crotalus; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D051379:Mice; D015230:Prostaglandin D2 / Q000096:biosynthesis*
D003435:Crotalid Venoms; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D015230:Prostaglandin D2