Effects Of Indomethacin Administration Research Articles

Effects of Indomethacin Administration on the Small Intestines of 40-Week-Old Mice

Effects of Indomethacin Administration on the Small Intestines of 40-Week-Old Mice

Effects of Indomethacin Administration on Some Biochemical and Brain Histological Changes in Male Rats

Effects of Indomethacin Administration on Some Biochemical and Brain Histological Changes in Male Rats

Bacterial translocation in experimental acute pancreatitis: Effects of indomethacin administration

Bacterial translocation in experimental acute pancreatitis: Effects of indomethacin administration

Effects of indomethacin administration on bone turnover and bone mass in adjuvant-induced arthritis in rats.

We examined the bone turnover and bone mass in adjuvant-induced arthritis in rats and assessed the effects of indomethacin in this model. One hundred ten SD rats, 6 weeks of age, were assigned to 11 groups and injected with adjuvant or solvent in the right foot. Adjuvant-injected rats were orally administered indomethacin at doses of 0 (vehicle), 0.1 (low), 0.5 (medium), and 1.5 (high) mg/kg body weight from the start (day 0). Animals were sacrificed on days 0, 14 (acute phase), and 28 (chronic phase). In the arthritic-control group, serum osteocalcin level and bone mineral content of the fourth lumbar body (L4) and the femur were significantly reduced on day 14. Serum alkaline-phosphatase was increased on day 28. Trabecular bone volume of L4 was decreased on day 14, and the value was further decreased on day 28. Bone formation rate (BFR/BS) was significantly reduced on day 14, and then osteoclast number (Oc.N/BS) increased on day 28. Indomethacin treatment dose-dependently prevented increases in paw volume and osteoclast number. In the high dose group, these indices were maintained at the same level with those in the normal group. However, indomethacin treatments were not able to maintain the parameters of bone formation such as serum osteocalcin and BFR/BS values, and the trabecular bone mass decrease was only partially prevented. These data clearly indicated both reduced bone formation and increased bone resorption as the causes of bone loss in adjuvant-induced arthritis in rats. Increased bone resorption seemed to be due to the increased activity of prostaglandins, but bone formation defect would be related to other factors in this animal model.

The effect of indomethacin administration on the splenic changes induced by estradiol supplementation in ovariectomized New Zealand white rabbits.

In an effort to elucidate the mechanism by which indomethacin (IN) lessens the stimulatory effect of estradiol (E2) on rabbit splenic red pulp macrophages (RPMs), 39 female New Zealand White rabbits were divided into 10 groups: ovariectomized (OVX) and OVX/IN at 0.1 and 5.0 mg/kg body weight (bw)/day; sham OVX (SOVX) and SOVX/IN at 0.1 and 5.0 mg/kg bw/day; OVX/25 mg E2 and OVX/25 mg E2/IN at 0.1 and 5.0 mg/kg bw/day; and intact control. Changes in RPM population in response to treatment were measured using a 0-4 histologic grade. Estradiol treatment resulted in increased RPM grade when compared to the OVX groups. Indomethacin addition lowered mean RPM grade in the SOVX/IN 5.0 group when compared to its E2 control group. Indomethacin administration had no significant effect on levels of prostaglandin E2 in spleen, urine, or blood. Hematocrits were reduced in both OVX and OVX/E2 groups; this decrease was exacerbated by the high IN dose. In summary, the results from this study suggest that the effect of IN on E2-induced RPM activation may be mediated through a nonprostaglandin pathway. The observed hematocrit changes are possibly the result of direct action of IN and E2 on erythrocytes, resulting in their accelerated clearance from the circulation by splenic RPM.

Accelerated Hematopoietic Recovery and Protective Effect of the Cyclooxygenase Inhibitor Indomethacin in Bacterial Infection of Neutropenic Mice

The effects of indomethacin administration on Pseudomonas aeruginosa infection were investigated in neutropenic mice. Cyclophosphamide-treated mice received the drug at 2.5 to 12 mg/kg according to different regimens, to be challenged with a lethal intraperitoneal inoculum of P. aeruginosa 5 days after myelosuppression. A single exposure of the neutropenic mice to 7 mg/kg indomethacin during the first 6 to 48 hr after myelosuppression was found to optimally restore the animals' antibacterial resistance, both in terms of survival of infected mice and clearance of the organisms from the peritoneal cavity. However, when administered 24 hr before challenge, the same drug dosage had no effect in enhancing survival. Cure was associated with accelerated hematopoietic recovery, as revealed by peripheral blood leukocyte counts, spleen weight and cellularity, cellular response to infection in the peritoneal cavity, and enumeration in vitro of bone marrow and splenic granulocyte-macrophage colony-forming cells. Following indomethacin administration, a rapid burst in the levels of colony-stimulating activity was detected in the bloodstream, and exposure of splenic macrophages or marrow cells to indomethacin in vitro was found to result in enhanced expression of transcripts specific for granulocyte-macrophage colony-stimulating factor. These data support the notion that the administration of cyclooxygenase inhibitors may be useful in promoting hematopoiesis and reducing the risk of opportunistic infections in myelosuppressed hosts.

Effect of indomethacin pretreatment on acute mortality in experimental brain injury.

The effect of indomethacin administration on the mortality rate of brain-injured rats was studied in four groups of animals subjected to a level of injury with a fluid-percussion apparatus predetermined to cause 50% mortality (50% lethal dose, or LD50). There were 24 animals in each of the following groups: 1) a control group, on which the LD50 was evaluated; 2) an ethanol-treated group with a mean blood serum level of 0.32 +/- 0.03 gm% (+/- standard error of the mean); 3) an indomethacin-treated group at a dose level of 3 mg/kg body weight administered intraperitoneally 10 to 15 minutes before injury; and 4) an indomethacin/ethanol-treated group. Significant differences in mortality rates were found in these experimental groups; namely, 50%, 58%, 8.3% (p less than 0.005), and 25% (p less than 0.05), respectively. The predetermined LD50 level of a 2.5- to 2.6-atm peak pressure pulse produced immediate apnea in all animals, which was either sustained (Type III), followed by temporary respiratory recovery (Type II), or followed by permanent resumption of breathing (Type I). The most important effect of indomethacin on respiratory function was manifested by a much higher percentage of Type I respiratory responses and a much lower percentage of Type II and III responses (hence a lower mortality rate). There was also a more rapid return to normal breathing in the postapneic period of recovery. Suppression of prostaglandin synthesis and of superoxide anion production at the of trauma may explain, at least in part, these favorable effects of indomethacin.

Effect of Indomethacin Administration on Glucose Homeostasis and Pancreatic Hormones in Lactating Goats1,2

To determine glucogenic and hormonal responses in ruminants to indomethacin, a prostaglandin synthetase inhibitor, four lactating Toggenburg goats were used in a crossover design. Fifteen milligrams of indomethacin or 3ml of saline were injected subcutaneously twice daily with propionate infused intrajugularly at a rate of 2mM/min for 75min as a challenge. Plasma glucose concentrations were increased by indomethacin injections. Plasma concentrations of insulin, glucagon, and 6-keto-prostaglandin F1α were not affected by indomethacin injections. Propionate infusion elevated plasma glucose, insulin, and glucagon concentrations. A decreased insulin release in response to propionate challenge was observed with indomethacin injections.

Indomethacin in canine acute hemorrhagic pancreatitis.

The effects of indomethacin administration on hemodynamics were investigated in canine acute hemorrhagic pancreatitis (AHP). Thirteen mongrel dogs were randomly divided into a fluid treatment group, an indomethacin prophylaxis group (IMP), and an indomethacin therapy (IM) group. Indomethacin (5 mg/kg) was administered as a bolus dosage 30 min before the induction of AHP in the IMP group. In the IM group, indomethacin was also given as a bolus (5 mg/kg) in 5 min starting 30 min after the induction of AHP. AHP was induced with a mixture of trypsin and sodium taurocholate infused into the pancreatic duct. Hemodynamics were monitored during the 4.5 h of surveillance time. Heart rate did not change significantly between the groups. Indomethacin prophylaxis maintained mean arterial pressure at a significantly higher level (P less than 0.05) and prevented the initial fall in blood pressure when compared to the fluid treatment or IM group. Indomethacin increased cardiac output (P less than 0.05) in the IM group, but did not differ significantly in the IMP group in comparison with the fluid treatment group. In conclusion, the inhibition of the initial fall in blood pressure by indomethacin in AHP suggests prostaglandins to play a role in hemodynamic changes and pancreatic shock to be "septic" as evaluated by hemodynamic changes.

The effects of indomethacin administration during pregnancy on women's and newborns' T-suppressor lymphocyte activity and on HLA class II expression by newborns' leukocytes.

It has been previously shown that T lymphocytes from human newborns and pregnant women exert a suppressive activity when assayed on the PWM-induced B cell maturation. The mechanisms of the suppression have remained entirely unknown. Prostaglandin E2, known to trigger T-cell mediated suppressive activity, may be involved. We took advantage of the treatment of pregnant women with indomethacin, because of premature labor or hydramnios, to investigate the role of prostaglandins in the activation of T suppressor (TS) activity. Administration of indomethacin (250 mg/day for 1-7 weeks, then 150 mg/day for 3-12 weeks) during the third trimester of pregnancy, abrogated the TS activity in the nine women and the three newborns tested. Abrogation of TS activity by indomethacin therapy led to normal PWM-induced B cell maturation in pregnant women but not in newborns. Moreover, the low expression of HLA class II antigens observed on normal newborn B lymphocytes and monocytes was corrected in newborns from indomethacin-treated mothers. Our results strongly suggest that prostaglandins may play a role in induction of TS activity observed in normal pregnant women and newborns and in the decreased expression of HLA class II antigens on newborns' leucocytes. Both phenomena could play a role in immunological interactions between mother and fetus.

The effects of indomethacin on plasma LH levels in female and male deermice ( [formula omitted

The purpose of this investigation was to determine (1) the approximate time of the preovulatory LH rise in cyclic deermice, (2) the effect of indomethacin administration on plasma LH levels during the expected preovulatory LH rise, and (3) the effect of indomethacin administration on plasma LH levels in castrated male deermice. The data indicate that the preovulatory LH rise occurred at about 2200 h on proestrus and that indomethacin pretreatment significantly reduced plasma LH levels during that time. In addition, indomethacin significantly reduced plasma LH levels in castrated male deermice. We conclude that plasma LH levels remain low throughout the estrous cycle with the exception of the preovulatory “surge”, that plasma LH levels in deermice are comparable to those reported for the rat, and that indomethacin pretreatment reduced plasma LH levels during periods when they were expected to be elevated (in castrated males and during the expected preovulatory LH rise in female deermice). The data are consistent with the hypothesis that the effect of indomethacin on plasma LH levels is due to an inhibitory effect on hypothalamic PG biosynthesis.

Effects of indomethacin administration on hepatic steroid and drug metabolism in male and female rats

Effects of indomethacin administration on hepatic steroid and drug metabolism in male and female rats

Basal and Histamine-Stimulated Human Gastric Acid Secretion

The effects of indomethacin administration on gastric acid secretion were studied in 22 patients with arthritic diseases. Twelve patients had rheumatoid arthritis, 8 had osteoarthritis, and 1 each had Reiter's syndrome and ankylosing spondylitis. Augmented histamine tests were performed before and after a 1-month trial of the drug, administered in dosage of 75 to 100 mg per day. Repeated augmented histamine tests also were performed in 11 control subjects after a similar interval of time. No statistically significant changes in basal or histamine-stimulated gastric acid secretion were found in either the patients with arthritis or the control subjects.