misoprostol and Necrosis

The aim of this study was to investigate the effect of misoprostol, silymarin or the co-administration of misoprostol + silymarin on the carbon tetrachloride (CCl(4))-induced hepatic injury in rats. Misoprostol (10, 100, 1000 microg/kg), silymarin (25 mg/kg) or misoprostol (100 microg/kg) + silymarin (25 mg/kg) was given once daily orally simultaneously with CCl(4) and for 15 days thereafter. The results showed that misoprostol (10, 100 or 1000 microg/kg) conferred significant protection against the hepatotoxic actions of CCl(4) in rats, reducing serum alanine aminotransferase (ALT) levels by 24.7%, 42.6% and 49.4%, respectively compared with controls. Misoprostol, given at 100 or 1000 microg/kg, decreased aspartate aminotransferase (AST) by 28 and 43.6% and alkaline phosphatase (ALP) by 19.3% and 53.4% respectively. Meanwhile, silymarin reduced ALT, AST and ALP levels by 62.7%, 66.1% and 65.1% respectively. The co-administration of misoprostol (100 microg/kg) and silymarin (25 mg/kg) resulted in 61.4%, 66.1% and 57.5% reduction in ALT, AST and ALP levels respectively. Histopathological alterations and depletion of hepatocyte glycogen and DNA content by CCl(4) were markedly reduced after treatment with misoprostol, silymarin or misoprostol + silymarin. Image analysis of liver specimens revealed a marked reduction in liver necrosis; area of damage: 32.4%, 24% and 10.2% after misoprostol (10, 100 or 1000 microg/kg), 7.2% after silymarin and 10.9% after treatment with misoprostol 100 microg/kg + silymarin, compared with CCl(4) control group (46.7%). These results indicate that treatment with misoprostol protects against hepatocellular necrosis induced by CCl(4). This study suggests a potential therapeutic use for misoprostol in liver injury.

Topics: Animals; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; DNA; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glycogen; Liver Diseases; Liver Function Tests; Male; Misoprostol; Necrosis; Protective Agents; Rats; Rats, Sprague-Dawley; Silymarin

Misoprostol is an important drug in obstetrics and gynecology because of its uterotonic and cervical-ripening activities. The side effects are dose-related, usually transitory, and well tolerated. The toxic dosage in humans is unknown, and there is no specific antidote.. An adolescent developed upper gastrointestinal bleeding after self-medication with misoprostol orally (12 mg) to cause abortion. She presented with multiorgan failure, acute abdominal signs, and hemodynamic instability. Emergency laparotomy showed gastric and esophageal necrosis. After several episodes of cardiac arrest, and despite resuscitation efforts, the patient died.. Temporal relationship (48 hours after the beginning of medication) strongly suggests that misoprostol was the agent directly involved in the maternal death. The mechanism implicating misoprostol in gastrointestinal ischemia and necrosis is unknown.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Adolescent; Diagnosis, Differential; Esophagus; Fatal Outcome; Female; Gastrointestinal Hemorrhage; Humans; Misoprostol; Multiple Organ Failure; Necrosis; Pregnancy; Stomach

To better understand the risk of fatal toxic shock caused by Clostridium sordellii in women who had a recent medical abortion with mifepristone and misoprostol.. We performed active and passive surveillance for cases of toxic shock associated with medical or spontaneous abortion. To identify the cause of toxic shock, immunohistochemical assays for multiple bacteria were performed on formalin-fixed surgical and autopsy tissues. We extracted DNA from tissues, performed Clostridium species-specific polymerase chain reaction assays, and sequenced amplified products for confirmation of Clostridium species.. We report four patients with toxic shock associated with Clostridium species infection after medical or spontaneous abortion. Two women had fatal Clostridium perfringens infections after medically induced abortions: one with laminaria and misoprostol and one with the regimen of mifepristone and misoprostol. One woman had a nonfatal Clostridium sordellii infection after spontaneous abortion. Another woman had a fatal C sordellii infection after abortion with mifepristone and misoprostol. All four patients had a rapidly progressive illness with necrotizing endomyometritis.. Toxic shock after abortion can be caused by C perfringens as well as C sordellii, can be nonfatal, and can occur after spontaneous abortion and abortion induced by medical regimens other than mifepristone and misoprostol.. III.

Topics: Abortifacient Agents; Abortion, Therapeutic; Administration, Intravaginal; Bacterial Toxins; Clostridium Infections; Clostridium perfringens; Clostridium sordellii; Fatal Outcome; Female; Humans; Laminaria; Mifepristone; Misoprostol; Necrosis; Pregnancy; Shock, Septic; Uterus

Treatment with non-steroid anti-inflammatory drugs associated with a prostaglandin analogue is common, but the potential cardiovascular effects are largely unknown. The authors report a case of myocardial necrosis and anaphylactic shock due to treatment with diclofenac and misoprostol. The reintroduction of the treatment in hospital led to the recurrence of the initial cutaneous and cardiac symptoms in this patient.

Topics: Aged; Anaphylaxis; Anti-Ulcer Agents; Diclofenac; Humans; Male; Misoprostol; Myocardium; Necrosis

In the present study, the protective effect of omeprazole on gastric mucosa injury induced by ethanol.HCl in rats and the putative mechanisms involved in this action were investigated. Misoprostol and ranitidine were used as reference drugs. The morphometric analysis of histological sections showed that omeprazole caused a significant reduction of mucosal necrotic damage, this effect being associated with a marked increase in Alcian blue recovery from gastric bound mucus. In addition, omeprazole elicited a significant inhibition of gastric acid secretion from pylorus-ligated rats. Misoprostol exerted similar effects to those obtained with omeprazole, even if the Alcian blue recovery and the acid output were affected to a lesser extent. By contrast, ranitidine failed to influence both the mucosal damage and the Alcian blue recovery, while it exerted a marked inhibition on acid secretion. The present results indicate that omeprazole is effective in protecting gastric mucosa from necrotic damage induced by ethanol.HCl and suggest that an enhancement of gastric mucus barrier may account for this protective action.

Topics: Animals; Ethanol; Gastric Acid; Gastric Mucosa; Gastritis; Hydrochloric Acid; Male; Misoprostol; Mucus; Necrosis; Omeprazole; Ranitidine; Rats; Rats, Wistar

The hepatoprotective effects of misoprostol on acetaminophen (APAP)-induced toxicity were studied in the rat. Liver injury was evaluated at 36 hr after APAP administration by measuring serum ornithine carbamoyltransferase (OCT) and alanine aminotransferase (ALT) levels, by using tetranitroblue tetrazolium (TNBT) staining and by histological analysis. After APAP administration, peak serum levels of the drug were detected at 15 min. Liver GSH was depleted from control levels of 448 +/- 48 micrograms/g to 82 +/- 2 micrograms/g (P < 0.01) within 3 hr. Serum ALT levels increased significantly after 16 hr and H&E staining revealed significant hepatic necrosis after 12 hr. Rats treated with misoprostol before and after APAP administration showed reduced OCT and ALT levels at 36 hr of overdose (454 +/- 446 IU/liter and 2571 +/- 2944 IU/liter, respectively) compared to those without misoprostol treatment (1348 +/- 480 IU/liter and 6077 +/- 3025 IU/liter, respectively, P < 0.01). TNBT staining showed a reduced area of damage from 28.6 +/- 22.3% to 7.3 +/- 8.9% (P < 0.01), and H&E staining also showed less extensive hepatic necrosis in rats treated with misoprostol before and after the overdose. In a time sequence study, misoprostol treatment starting within 10 hr of overdose showed the same protective effect as when it was given before and after APAP ingestion. No protection was detected when the treatment was started during the development of hepatic injury. However, misoprostol given when injury was established seemed to be protective. Our results show that misoprostol protects the liver against APAP-induced injury if given within 10 hr of overdose.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetaminophen; Alanine Transaminase; Animals; Disease Models, Animal; Drug Overdose; Liver; Male; Misoprostol; Necrosis; Ornithine Carbamoyltransferase; Rats

This study reports the histological effects of topical misoprostol, a synthetic PGE1 analog, administered in varying dosages on the resting canine gastric mucosa. Misoprostol did not macroscopically or microscopically damage the mucosa but its presumed permeability effects on the gastric vasculature induced marked edema of the mucosa and submucosa. Consistent features included increased thickness of both layers, dilated interglandular regions of the lamina propria, marked subepithelial edema, reduced depth and width of gastric foveolae, vasodilation of the vascular channels, reduced height of surface epithelial cells, swelling of their basolateral intercellular spaces, and increased amounts of surface adherent mucus. It is speculated that the mucosal edema, in addition to an increased mucus layer, may be important in the mechanism of gastric cytoprotection by increasing the distance of penetration or absorption for a mucosal-damaging agent, diluting its concentration, and disseminating any focal accumulations of red blood cells.

Topics: Administration, Topical; Animals; Dogs; Gastric Mucosa; In Vitro Techniques; Misoprostol; Necrosis

The role of the prostaglandin E1 (PGE1) analog misoprostol in hepatocellular injury induced by carbon tetrachloride (CCl4) was investigated in isolated rat hepatocytes. Exogenously added PGE1 at nanomolar concentrations attenuated significantly liver cell injury and death induced by CCl4. This cytoprotection, however, was accomplished only when a "crude" liver cell preparation was used. When the small nonparenchymal liver cell fraction (Kupffer and endothelial cells) was eliminated, the beneficial effects of PGE1 could no longer be observed. The results indicate that nonparenchymal liver cells play an important role in the cytoprotection provided by PGE1 at the initial stage of cellular damage in our isolated rat liver cell system.

Topics: Alprostadil; Animals; Carbon Tetrachloride; In Vitro Techniques; Liver; Male; Misoprostol; Necrosis; Rats; Rats, Inbred Strains

Mycobacterial lesions and skin sites challenged with soluble mycobacterial antigen are very sensitive to the necrotizing effect of tumour necrosis factor (TNF). We have used a model that permits separate quantitative assessment of swelling and haemorrhage to show that when these reactions are elicited in mice that have not been deliberately immunized, pretreatment of the mice with lipopolysaccharide (LPS), or with a MoAb to CR3 which blocks emigration of myeloid cells into the tissues, will block both the swelling and the haemorrhage. On the other hand, treatment with an inhibitor of platelet-activating factor (PAF), or with misoprostol (a synthetic prostaglandin E1 analogue), or with cobra venom factor (CVF) which depletes complement, preferentially blocks the haemorrhagic component, while leaving the swelling relatively unaltered. As swelling occurs before the haemorrhage is seen, it is possible that these factors act at a late stage in the cascade of events leading to the tissue damage. However, LPS and CVF were able to inhibit swelling and haemorrhage in the massive reactions elicited in pre-immunized animals, whereas the PAF inhibitor had no detectable effect.

Topics: Animals; Antigens, Bacterial; Complement System Proteins; Elapid Venoms; Female; Hemorrhage; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Misoprostol; Mycobacterium; Necrosis; Platelet Activating Factor; Skin Diseases; Tumor Necrosis Factor-alpha

This study was designed to determine whether prostaglandins can stimulate the repair of human duodenal epithelium. Ten healthy volunteers were given 50 ml 40% ethanol through an endoscope onto the duodenal mucosa 1-7 cm from the pyloric sphincter; 3 min later, misoprostol (200 micrograms) or inert vehicle (5 ml) was given locally in the same way. One and 5 h later, endoscopy was repeated to evaluate the damage. The conditions of the mucosa were evaluated by endoscopy and by scanning and transmission electron microscopy in biopsies taken at time 0 and 3 min, 1 and 5 h after ethanol. The study was double-blind with a cross-over balanced design. Three minutes after ethanol administration, the duodenal mucosa showed hyperemia with hemorrhagic lesions. Under the electron microscope, the lesions were caused by vascular engorgement or red blood cell extravasation into the submucosa; the epithelium underlining lesions showed loss of superficial cells and damage to the upper layer of the mucosa. One hour after ethanol, there was a striking difference between the two treatment groups, with a substantial recovery of the duodenal epithelium in the misoprostol-treated volunteers. Although spontaneous recovery was evident in the control group, there was also a significant difference at 5 h. Our results suggest that prostaglandins are able to stimulate the recovery of the duodenal epithelium after acute damage.

Topics: Alprostadil; Anti-Ulcer Agents; Double-Blind Method; Duodenoscopy; Duodenum; Epithelium; Ethanol; Female; Humans; Intestinal Mucosa; Male; Misoprostol; Necrosis; Reference Values

Six percent hydrogen peroxide (H2O2) was used as a generator of the *OH free radical, and as an aggressor of gastric mucosa, in 100 Wistar rats. The mucosal cytoprotector effect of sucralfate, misoprostol, enprostil, cimetidine, ranitidine, famotidine and 10% aluminum sulphate yielded almost complete macroscopic and histological protection to the gastric mucosa. Misoprostol or enprostil gave partial protection whereas the H2 blockers aggravated the gastric necrotic lesions produced by the H2O2. We conclude that sucralfate is a true anti-oxidant that protects the gastric mucosa through its aluminum and sulphydril components, the increment of gastric mucins and endogenous PGs.

Topics: Alum Compounds; Animals; Antioxidants; Cimetidine; Enprostil; Famotidine; Female; Free Radicals; Gastric Mucosa; Glycosaminoglycans; Hydrogen Peroxide; Hydroxides; Male; Misoprostol; Necrosis; Ranitidine; Rats; Rats, Inbred Strains; Sucralfate

The cytoprotective effects on the gastric mucosa of the Bromocriptine, a peripheral dopaminergic receptor agonist compared with Misoprostol against ethanol-induced injury were studied. Pretreatment with SCH 23390 (a DA1 receptor antagonist) and Domperidone (a DA2 receptor antagonist), showed that Misoprostol was peripheral dopaminergic receptor dependent in the gastric cytoprotective mechanism, and that Bromocriptine was a selective peripheral DA2 receptor agonist in the gastric cytoprotection mechanism; as well as, indomethacin pretreatment, showed that peripheral DA2 receptors were endogenous prostaglandin dependent. In conclusion, a prostaglandin-dopaminergic mechanism was postulated in gastric cytoprotection.

Topics: Alprostadil; Animals; Antipsychotic Agents; Benzazepines; Bromocriptine; Domperidone; Ethanol; Gastric Mucosa; Misoprostol; Necrosis; Random Allocation; Rats; Rats, Inbred Strains; Receptors, Dopamine

Fasted rats were given a single oral dose of one of the following: a synthetic prostaglandin E1 analog, misoprostol (low dose = 100 micrograms/kg, or high dose = 1 mg/kg), cimetidine (low dose = 100 micrograms/kg, or high dose = 50 mg/kg), phosphate buffer, or absolute ethanol. A second group of rats received a single oral dose of misoprostol, cimetidine, or phosphate buffer intragastrically, followed 30 min later by a second oral dose of absolute ethanol. Stomachs were either surgically removed and examined grossly or were fixed in situ and prepared for histological observation 15 or 30 min after the initial dose, or 15 or 30 min after the second dose. Absolute ethanol alone produced grossly visible hemorrhagic lesions and extensive hyperemia and microscopic damage to the glands, which was largely confined to the crests of the rugae. Microscopic examination of nonhemorrhagic areas showed extensive damage of the superficial and gastric pit epithelial cells as well as some endothelial cells and adjacent structures in the lamina propria. Pretreatment with phosphate buffer, or either dose of cimetidine, did not obviate the gross hemorrhagic lesions or the histologic damage produced by absolute ethanol. Both the low and high doses of misoprostol protected the stomach against ethanol-induced gross hemorrhagic lesions but did not completely protect against microscopic damage to the superficial mucosa.. the protective action of misoprostol involves mechanisms that prevent hemorrhagic lesions but do not completely shield the superficial mucosa from damage. These mechanisms appear to be independent of misoprostol's antisecretory effects.

Topics: Alprostadil; Animals; Anti-Ulcer Agents; Buffers; Cimetidine; Ethanol; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Misoprostol; Necrosis; Phosphates; Rats; Rats, Inbred Strains