Mechanistic evaluation of gastro-protective effects of KangFuXinYe on indomethacin-induced gastric damage in rats / 中国天然药物

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 gastro-protective 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), different dosages of KFX (2.57, 5.14 and 10.28 mL·kg, respectively) plus indomethacin, and sucralfate (1.71 mL·kg) 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 E (PGE) 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) 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).

The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm2); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm2); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels.

Role of the NO/K ATP pathway in the protective effect of a sulfated-polysaccharide fraction from the algae Hypnea musciformis against ethanol-induced gastric damage in mice

Seaweeds are the most abundant source of polysaccharides such as alginates and agar, as well as carrageenans. This study aimed to investigate the gastroprotective activity and the mechanism underlying this activity of a sulfated-polysaccharide fraction extracted from the algae Hypnea musciformis (Wulfen) J.V. Lamour. (Gigartinales-Rhodophyta). Mice were treated with sulfated-polysaccharide fraction (3, 10, 30, and 90 mg/kg, p.o.) and, after 30 min, they were administered 50% ethanol (0.5 mL/25 g, p.o.). After 1 h, gastric damage was measured using a planimeter. In addition, samples of the stomach tissue were obtained for histopathological examination and for assays to determine the glutathione and malondialdehyde levels. Other groups of mice were pretreated with N G-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p.), aminoguanidine (100 mg/kg, i.p.), or glibenclamide (10 mg/kg, i.p.). After 30 min to the aminoguanidine group and 1 h to the other groups, sulfated-polysaccharide fraction (30 mg/kg, p.o.) was administered and gastric damage was induced as described above. Sulfated-polysaccharide fraction prevented ethanol-induced gastric injury in a dose-dependent manner. However, treatment with L-NAME or glibenclamide reversed this gastroprotective effect. Administration of aminoguanidine did not influence the effect of sulfated-polysaccharide fraction. Our results suggest that sulfated-polysaccharide fraction exerts a protective effect against ethanol-induced gastric damage via activation of the NO/K ATP pathway.

Suicidal ingestion of potassium permanganate / 世界急诊医学杂志（英文）

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.

Comparison of Indomethacin, Diclofenac and Aspirin-Induced Gastric Damage according to Age in Rats

BACKGROUND/AIMS: Aging gastric mucosa is known to have decreased mucosal defenses and increased susceptibility to injury by nonsteroidal anti-inflammatory drugs. Depending on the type of nonsteroidal anti-inflammatory drug (NSAID), the underlying mechanisms and the extent of damage to the stomach or intestine may differ. This study was performed to evaluate the acute gastric damage caused by different doses of indomethacin, diclofenac and aspirin in rats of various ages. METHODS: For the acute models, indomethacin (10, 20 or 40 mg/kg), diclofenac (40 or 80 mg/kg) or aspirin (100 mg/kg) was given to 7- and 25-week-old and 1-year-old Sprague-Dawley rats by intragastric gavage. The gross ulcer index, damage area as assessed by imaging, histological index, myeloperoxidase (MPO) activity, and cytosolic phospholipase A2 (cPLA2) levels were measured after 24 hours. RESULTS: The gross ulcer index and damage area increased with age in the presence of three NSAIDs (p<0.05). The increases in MPO levels induced by diclofenac and aspirin were significantly higher in 1-year-old than 7-week-old rats (p<0.05). cPLA2 expression induced by indomethacin (10 and 40 mg/kg) was greater in the 1-year-old rats, compared with 7-week-old rats (p<0.05). CONCLUSIONS: NSAID-induced acute gastric damage increased in a dose- and age-dependent manner.