Eicosanoid and gastroprotection by copper derivatives and NDGA.
We investigated the effect of oral administration of graded doses of: nordihydroguaiaretic acid (NDGA), CuNSN, a bis(2-benzimidazolyl)thioether and CuCl2 on ethanol-induced gastric damage in the rat and the role of leukotrienes and prostaglandins in attenuating this damage. In the experiments we determined ex-vivo eicosanoid release in the rat gastric mucosa pretreated with the above-mentioned compounds. The results indicate that the gastric lesion is accompanied by an increase in mucosa-synthesize LTC4, while PGE2 formation remains unchanged. Pretreatment with NDGA, CuNSN and CuCl2, protects the gastric mucosa from damages and reduces the increase in LTC4 mucosal formation. CuNSN and CuCl2 increase the PGE2 release, while NDGA has no effect on this pathway. These results suggest that one of the possible mechanisms of the NDGA protective effect is related to the inhibition of LTC4 formation, while the PGE2 increase in synthesis together with the leukotriene inhibition could contribute to the protective effect of CuNSN and CuCl2.
Franco
L
L
Institute of Pharmacology, University of Verona, Policlinico di Borgo Roma, Italy.
Velo
G P
GP
D000284:Administration, Oral; D000818:Animals; D003300:Copper / Q000008:administration & dosage / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007213:Indomethacin / Q000008:administration & dosage / Q000633:toxicity; D017997:Leukotriene C4 / Q000378:metabolism; D008297:Male; D009637:Masoprocol / Q000008:administration & dosage / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009942:Organometallic Compounds; C095494:bis(2-benzimidazolyl)thioter copper complex; D017997:Leukotriene C4; D000431:Ethanol; D003300:Copper; D009637:Masoprocol; D015232:Dinoprostone; C029892:cupric chloride; D007213:Indomethacin