Tablet of Spondias mombin L. Developed from Nebulized Extract Prevents Gastric Ulcers in Mice via Cytoprotective and Antisecretory Effects.

Spondias mombin L. (Anacardiaceae) has a worldwide distribution and is present in all regions of Brazil. Its leaves, flowers and bark are used as teas in folk medicine to treat diseases of the digestive system. This study aimed to evaluate the acute non-clinical toxicity, gastroprotective activity, and the related mechanisms of action of nebulized extract and tablets based on dried Spondias mombin (SmNE). SmNE screening showed the presence of flavonoids (0.65%), polyphenols (25.50%), where the major compound is gallic acid. In the acute oral toxicity assay, a dose of 2000 mg/kg of SmNE administered orally in Swiss mice did not induce any behavioral changes. SmNE (250 or 500 mg/kg p.o) significantly reduced the ulcerative lesion area when compared to the control group in ethanol and non-steroidal anti-inflammatory drug (NSAIDs) models. Results showed that treatment with SmNE (250 mg/kg) reduced acid secretion and gastric content, accompanied with an increase in pH. Previous administration of indomethacin and glibenclamide reversed the protection provided by SmNE, confirming the participation of prostaglandins (PGs) and ATP-sensitive potassium channels (KATP) in its gastroprotective effect. The SmNE tablets met the pharmacopeial quality requirements with gastroprotective activity and similar protection in comparison to the isolated extract administrated. In conclusion, SmNe has a gastroprotective activity related to cytoprotective mechanisms, such as the participation of endogenous prostaglandins and KATP channels, having an anti-secretory effect with systemic action. The formulation obtained presented gastroprotective effects similar to the administration of the extract, the tablets showed favorable compression characteristics by the direct route and met the pharmacopeial quality requirements.

Bombax Costatum extract abrogates piroxicam-mediated hepatic and gastric toxicities in rats.

OBJECTIVE: Concurrent administration of orthodox drugs and herbs is common in tropical Africa. This study investigates the effect of co-administration of piroxicam and Bombax costatum on hepatic and gastric toxicities and levels of oxidative stress markers. MATERIALS AND METHODS: Twenty male wistar rats were grouped into four. Rats in group one were administered 1mL/kg distilled water as normal control; group two were treated with 400mg/kg of extract; group three were treated with 20mg/kg of piroxicam; while those in group four were treated with both extract and piroxicam at 400mg/kg and 20mg/kg, respectively. All treatments were given orally for 14 days. At the end of the treatment period, the rats were euthanised; blood samples and stomach were collected for determination of hepatic and gastro-toxicity alongside with oxidative stress markers. RESULTS: Treatment with piroxicam alone shows the presence of oxidative stress with marked hepatic and gastric toxicities. Oxidative stress markers, hepatic and gastric toxicity indices after treatment with extract alone and in combination with piroxicam appear like that of the control group. CONCLUSION: Concurrent administration of piroxicam and Bombax costatum prevents piroxicam-induced hepatic and gastric toxicities with a positive effect on antioxidant levels. This may indicate important health benefits of this drug-herb combination.

Histological study of the protective role of ginger on piroxicam-induced liver toxicity in mice.

BACKGROUND: Piroxicam is a non-steroidal anti-inflammatory drug widely used in rheumatic diseases. It has analgesic and antipyretic activity, and is one of the drugs being introduced in clinical practice. Piroxicam-hepatotoxicity has been reported as one of its principal side effects. Several natural antioxidants were found to be effective against drug induced toxicity. Ginger is known by its antioxidant activities and hepatoprotective effects. The present study aimed at studying the protective effect of Ginger on Piroxicam-induced histopathological changes in livers of male mice. METHODS: Forty adult mice were randomly divided into 4 groups: Group I served as the control group. Group II received Ginger orally in a dose of 200 mg/kg per day for four weeks. Group III received Piroxicam intraperitoneally in a dose of 0.3 mg/kg per day for four weeks. Group IV received (Piroxicam + Ginger). At the end of the experiment, liver functions were estimated and then the liver was removed, and sampled for histopathological, immunohistochemistry and biochemical studies. RESULTS: Administration of ginger decreased elevated serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and immunoexpression of the proapoptotic protein (Bax), induced by piroxicam. It increased immunoexpression of the antiapoptotic protein (Bcl2). It also ameliorated the morphological changes induced by piroxicam. CONCLUSION: Piroxicam has toxic effects on the liver as indicated by biochemical, histological and immunohistochemical results. Ginger has protective effects against piroxicam-hepatotoxicity by reducing serum marker enzymes, liver fibrosis and apoptosis.

Gastroprotective effect of zinc acexamate against damage induced by nonsteroidal antiinflammatory drugs. A morphological study.

The gastroprotective effect of zinc acexamate against gastric damage induced by different nonsteroidal antiinflammatory drugs (indomethacin, diclofenac, and piroxicam) was morphologically assessed in the rat glandular stomach by light and scanning electron microscopy. In addition, the capability of these antiinflammatory drugs to inhibit gastric prostaglandin E2 production was compared with their ability to induce gastric lesions. Microscopically, disappearance of mucus glycoprotein and exfoliation of the mucosal surface were the most common findings. Surface ultrastructural lesions varied from minimal lesions of the surface epithelial cells to deep erosions of the gastric mucosa with release of associated cellular elements and sloughing of the denuded lamina propria. Diclofenac elicited the most powerful inhibitory activity on mucosal prostaglandin E2 (98% inhibition vs control), closely followed by piroxicam (97.8%) and indomethacin (91.05%). Pretreatment of animals with zinc acexamate significantly increased the presence of mucus glycoprotein, maintained the continuity of the surface epithelial cells, and decreased the depth of the mucosal erosions. The degree of protection exerted by zinc acexamate varied with the antiinflammatory, but was always evident.

Overview of the pharmacological properties, pharmacokinetics and animal safety assessment of lornoxicam.

Lornoxicam is a new, highly potent antirheumatic agent which is an oxicam derivative. Although highly potent as a cyclo-oxygenase inhibitor, the compound does not cause inhibition of 5-lipoxygenase and does not appear to shunt arachidonic acid through this cascade. This powerful inhibition of cyclo-oxygenase has manifested itself as highly potent analgesic and anti-inflammatory effects in animal studies and also prevented the bone destruction which normally occurs in the adjuvant polyarthritic rat. To explain this finding, studies have demonstrated that lornoxicam inhibits polymorphonuclear (PMN)-leukocyte migration; inhibits the release of superoxide from human PMN-leukocytes; inhibits the release of platelet derived growth factor (PDGF) from human platelets and stimulates the synthesis of proteoglycans in cartilage in tissue culture. Lornoxicam is well absorbed and has a plasma t1/2 in man of 4 hours which is distinctly different from other oxicams. It is metabolized in animals and in man to the 5'-hydroxy-metabolite which is inactive in pharmacological tests. In vitro and in vivo animal safety studies have demonstrated both subchronically and chronically that lornoxicam manifests no unusual toxicity, is not a mutagen nor is it tumorigenic and causes no fetal teratogenicity in reproduction studies.