Mechanistic evaluation of gastro-protective effects of KangFuXinYe on indomethacin-induced gastric damage in rats

KangFuXinYe(KFX),the ethanol extract of the dried whole body of Periplaneta americana,is a well-known important Chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for many years in China.However,its therapeutic effect and mechanism are not yet well understood.Thus,the aim of this study was to investigate the gastroprotective effects of KangFuXinYe(KFX)in indomethacin-induced gastric damage.Rats were randomly divided into six groups as follows:control,treated with indomethacin(35 mg·kg^-1),different dosages of KFX(2.57,5.14 and 10.28 mL·kg^-1,respectively)plus indomethacin,and sucralfate(1.71 mL·kg^-1)plus indomethacin.After treatment,rat serum,stomach and gastric homogenates were collected for biochemical tests and examination of histopathology firstly.Rat serum was further used for metabolomics analysis to research possible mechanisms.Our results showed that KFX treatment alleviated indomethacin-induced histopathologic damage in rat gastric mucosa.Meanwhile,its treatment significantly increased cyclooxygenase-1(COX-1),prostaglandin E2(PGE2)and epidermal growth factor(EGF)levels in rat serum and gastric mucosa.Moreover,KFX decreased cyclooxygenase-2(COX-2)and interleukin-6(IL-6)levels.Nine metabolites were identified which intensities significantly changed in gastric damage rats,including 5-hydroxyindoleacetic acid,indoxylsulfuric acid,indolelactic acid,4-hydroxyindole,pantothenic acid,isobutyryl carnitine,3-methyl-2-oxovaleric acid,sphingosine 1-phosphate,and indometacin.These metabolic deviations came to closer to normal levels after KFX intervention.The results indicate that KFX(10.28 mL·kg^-1)exerts protective effects on indomethacin-induced gastric damage by possible mechanisms of action(regulating tryptophan metabolism,protecting the mitochondria,and adjusting lipid metabolism,and reducing excessive indomethacin).

Suicidal ingestion of potassium permanganate

BACKGROUND:Potassium permanganate is used clinically as an antiseptic and antifungal agent.Ingestion of potassium permanganate may result in damage to the upper gastrointestinal tract.Burns and ulceration of the mouth,esophagus and stomach occur due to its action.Emergency endoscopy is useful to assess the severity of damage and also to guide management.METHODS:We reported a patient presenting to the emergency department after suicidal ingestion of potassium permanganate.RESULTS:After treatment,the patient was discharged home on the 7th day after admission.CONCLUSION:Early emergency endoscopy should be considered to determine the extent of upper gastrointestinal damage in the emergency department.

Organic carbon monoxide prodrug, BW-CO-111, in protection against chemically-induced gastric mucosal damage

Metal-based carbon monoxide(CO)-releasing molecules have been shown to exert antiinflammatory and anti-oxidative properties maintaining gastric mucosal integrity.We are interested in further development of metal-free CO-based therapeutics for oral administration.Thus,we examine the protective effect of representative CO prodrug,BW-CO-111.in rat models of gastric damage induced by necrotic ethanol or aspirin,a representative non-steroidal anti-inflammatory drug.Treatment effectiveness was assessed by measuring the microscopic/macroscopic gastric damage area and gastric blood flow by laser flowmetry.Gastric mucosal mRNA and/or protein expressions of HMOX1,HMOX2,nuclear factor erythroid 2-related factor 2,COX1,COX2,iNos,Anxa1 and serum contents of TGFB1,TGFB2,IL1 B,IL2,IL4,IL5,IL6,IL10,IL12,tumor necrosis factorα,interferonγ,and GM-CSF were determined.CO content in gastric mucosa was assessed by gas chromatography.Pretreatment with BW-CO-111(0.1 mg/kg,i.g.)increased gastric mucosal content of CO and reduced gastric lesions area in both models followed by increased GBF.These protective effects of the CO prodrug were supported by changes in expressions of molecular biomarkers.However,because the pathomechanisms of gastric damage differ between topical administration of ethanol and aspirin,the possible protective and anti-inflammatory mechanisms of BW-CO-111 may be somewhat different in these models.

Effect of oxytocin on gastric ischemia-reperfusion injury in rats

The effect of peripherally administered oxytocin(OT)on gastric ischemia-reperfusion injury(GI-RI)and its possible mechanism were investigated.The Sprague-Dawley(SD)rats were randomly divided into different treatment groups(n=6).The animal GI-RI model was established by clamping the celiac artery for 30 min to induce ischemia and then released to allow reperfusion for 1 h,and the degree of GI-RI was assessed by scoring the gastric mucosal damage index(GMDI),the gastric fluid output,gastric fluid output,gastric acidity were measured and the surgical preparations of vagotomy and sympathectomy were used to investigate the possible mechanism of OT on GI-RI.The results were as follows.Compared with the control group(NS plus GI-R only,GMDI 121.33P10.40,n=6),the intra peritoneal(ip)administration of oxytocin(20,100μg/0.5 mL)obviously attenuated GI-RI(P<0.05),GMDI were 82.33P14.26,53.5P5.58 respectively(n=6);the gastric fluid output and the gastric acidity(evaluated by pH)of the control group were(430.17P87.36)μL,1.55P0.25(n=6),and those of the OT group were(102.45P48.00)μL,2.65P0.40(n=6)res pectively;differences had statistical significance(P<0.01).The effect of oxytocin was reversed by atosiban,a selective oxytocin receptor antagonist.The GMDI of the group given atosiban 10 min before OT was 138.17P24.06(n=6),which had no significant difference with the control group.Oxytocin further attenuated GI-RI after vagotomy and sympathectomy(GMDI 6.83P8.89,29.67P5.54,n=6),compared with the GI-R group and the oxytocin group(P<0.01).These results indicated that the oxytocin could significantly protect gastric mucosal against injury induced by ischemia-reperfusion,and the oxytocin receptor was involved.This effect of oxytocin may be mediated through the vagus and sympathetic nerve,and then lead to the reduction of gastric juice output and the depression of gastric acidity.