Effects of cupric chloride and tamrabhasma, a traditional Indian preparation of copper, on eicosanoid production by human gastric and colonic mucosa.
Tamrabhasma is a traditional copper oxide-containing Indian preparation which has anti-ulcer activity. We have studied the effect of tamrabhasma and CuCl2.2H2O on prostaglandin formation by human gastric and colonic mucosa and submucosa, as prostaglandins have mucosal protective activity, and their release may contribute to the anti-ulcer effect. With the gastric mucosa, tamrabhasma 10 micrograms mL-1, but not 0.1 or 1 microgram mL-1, increased prostaglandin E (PGE) concentration by 38% (P < 0.05), with little or no effect on 6-keto-PGF1 alpha, thromboxane B2 or the leukotriene (LT) LTC4/LTD4. CuCl2.2H2O (10 micrograms mL-1) increased 6-keto-PGF1 alpha by 46% (P < 0.05), but 0.1, 1, 50 and 250 micrograms mL-1 did not significantly affect any of the prostanoids, and only the highest concentration reduced the amount of LTC4/LTD4. In the colon mucosa, tamrabhasma (0.1-10 micrograms mL-1) or CuCl2.2H2O (10-50 micrograms mL-1) increased all the prostanoids and this effect was greater than in the gastric mucosa but there was no significant change in LTC4/LTD4. CuCl2.2H2O showed a bell-shaped concentration-effect curve, with no significant effect at lower and higher amounts. Indomethacin (0.1-10 micrograms mL-1) caused a concentration-dependent reduction in the prostanoid amounts. The effect of tamrabhasma was probably not only due to the presence of Cu2+, as tamrabhasma was more effective than CuCl2.2H2O alone; in addition the solubility of CuO is very low. Increased prostanoid levels might explain, at least partly, the gastric mucosal protection by tamrabhasma. The results in the colon, however, raise the possibility that tamrabhasma should be examined for the treatment of inflammatory bowel disease.
Department of Surgery, King's College School of Medicine and Dentistry, Rayne Institute, London, UK.
R K
RK
Goel
I A
IA
Tavares
A
A
Bennett
D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D004338:Drug Combinations; D015777:Eicosanoids / Q000096:biosynthesis*; D005296:Ferrous Compounds / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D011863:Radioimmunoassay
D000897:Anti-Ulcer Agents; D004338:Drug Combinations; D015777:Eicosanoids; D005296:Ferrous Compounds; D011453:Prostaglandins; C040566:tamrabhasma; D003300:Copper; D001205:Ascorbic Acid; C029892:cupric chloride; D007213:Indomethacin