Ulcerogenic effects of indomethacin in pregnant rats.

The high risk of developing gastric ulcers by various non-steroidal anti-inflammatory drugs has affected their common application in the treatment of collagen diseases like arthritis. Indomethacin, a potent anti inflammatory agent, has been found to induce gastric irritation and ulceration (1). In humans, it is expected that pregnancy which may exert physiologic stress would aggravate gastric ulcer. Instead, pregnant mothers are protected from gastric ulceration under normal conditions. Stress or restraint has been found also to induce ulcers in laboratory animals (2, 3). In the mechanism of indomethacin-induced ulcers, Djahanguiri et al. (4) found adrenalectomy to have no effect, while Urushidani (5) contrasted these findings by implicating the deficiency of glucocorticoids. In another study, Vane (6) proposed the inhibition of prostaglandin biosynthesis as a mechanism of action for aspirin-like drugs. Several other drugs have been claimed to aggravate or suppress indomethacin-induced ulcers (4). The present study was undertaken to investigate the ulcerogenic effects of indomethacin in pregnant rats and to suggest a possible mechanism. Forty mature female Wistar rats (150-190 g) were kept with mature males capable of mating (number of females were more than males). Vaginal smears were examined on the following morning, and the day on which sperms were detected in the smear was considered to be the first day of pregnancy (7). The animals were separated into two groups: 20 were treated during mid-term (9-10 days of pregnancy), and the other 20 mice treated with drugs during late pregnancy (19-20 days of pregnancy). Ten mice from such a group served as the control, while the other ten mice received the drug. Indome thacin (Polfa) at a dose of 15 mg/kg in 1 % CMC suspension containing a trace of Tween 80 was used to induce ulcers using the method of Urushidani. The method of Main and Whittle (8) was used to determine the ulcer index. The control group was treated with 0.5 ml/kg of 1% CMC sus pension containing a trace of Tween 80. Results are shown in Table 1 as the mean ulcer index ±S.E. The study was repeated with 20 nonpregnant rats. Ten of them received single s.c. doses of 15 mg/kg of the drug, while the rest served as the control and were treated with 0.5 ml/kg containing a trace of Tween 80 in 1 % CMC. The results were compared with the previous work by Aguwa and Mittal (9). The significance of the …