Possible Protective Effect of TNF-α Inhibition and Triad NO/cGMP/VEGF Activation on Gastric Ulcer in Rats

A peptic ulcer is one of the world's major gastrointestinal disorders, embracing both gastric and duodenal ulcers, and affecting 10% of the world population. The current study aimed to investigate the possible protective effect of tadalafil and pentoxifylline on indomethacin-induced peptic ulcers. Male albino rats were divided into five groups. Control group, ulcerated group. Indomethacin+ Tadalafil, in which animals were pretreated with tadalafil orally before indomethacin. Indomethacin+ PTX, in which animals were pretreated with PTX orally before indomethacin. Indomethacin + combination of two drugs. Indomethacin revealed histopathological changes, ulcer scoring, and ulcer index were markedly increased. Serum levels of PGE2 and HO-1 were significantly decreased. The ulcerogenic also induced marked oxidative stress as evident from the increased MDA, decreased in gastric GSH content and SOD activity, while the gastric MPO was increased. Gastric NO content was decreased and the expression of VEGF was downregulated while the TNF-a level was dramatically increased. Pretreatment of the ulcerative group by either tadalafil or pentoxifylline or their combination improved all these pathological changes. Tadalafil or PTX may have a role in protecting gastric mucosa damage caused by indomethacin which may be useful in the future for the treatment of gastric ulceration.

Combined but not single administration of vitamin C and l-carnitine ameliorates cisplatin-induced gastric mucosa damage in male rats

Although cisplatin is a potent anticancer drug, it instigates oxidative and pro-inflammatory reactions that pose significant and distressing clinical symptoms. Therefore, this study investigated the effects of vitamin C and (or) l-carnitine on cisplatin-induced gastric mucosa damage in rat. The rats were allocated into 6 groups (n = 5). The control group received distilled water, while the treatment groups received cisplatin alone (CIP), or cisplatin with vitamin C, l-carnitine, or their combination. Cisplatin caused disruption of the gastric mucosa histoarchitecture and altered the mucus barrier function. Moreover, the stomach tissue of the CIP-treated group showed increased levels of oxidative stress markers (malondialdehyde and H2O2) and decreased activities of antioxidant (superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase) and non-antioxidant (reduced glutathione) enzymes. These deleterious events were accompanied with significant increases in pro-inflammatory cytokines and inflammatory infiltration markers, myeloperoxidase and inducible nitric oxide synthase. However, the administration of both vitamin C and l-carnitine, and not either of the two showed additive effects in attenuating the adverse effects of cisplatin. The histological results agreed with the biochemical assays. The study concluded that the combined administration of vitamin C and l-carnitine, but not the single therapy, could prevent the adverse effects of cisplatin on gastric tissue.

IMMUNOHISTOCHEMICAL APPROACH REVEALS LOCALIZATION OF CYSTATHIONINE-?-LYASE AND CYSTATHIONINE-ß-SYNTHETASE IN ETHANOL-INDUCED GASTRIC MUCOSA DAMAGE IN MICE

Context Hydrogen sulphide (H2S) has been proved to be a neuromodulator and contributes to the maintenance of gastric mucosal integrity in damage caused by anti-inflammatory nonsteroidal drugs. Previously, we demonstrated that H2S synthesis is essential to gastric protection against ethanol. Objective To better understanding the role of H2S and the detailed localization of its production in both normal and injured stomach due to ethanol injection, we studied the expression of cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS) isoforms in gastric mucosa of mice treated with saline or 50% ethanol. Methods Mice were treated by gavage with saline or 50% ethanol (0.5 mL/25 g). After 1 hour, mice were sacrificed, and gastric tissue was evaluated by histological and immunohistochemical analysis specific for CSE and CBS. Results We have demonstrated a non-specific expression of CBS in the normal gastric mucosa and expression of CSE occurring mainly in the parietal cells of the animals treated with ethanol. Conclusion Thus, we demonstrated that the expression of CBS appears to be constitutive and diffuse across the gastric epithelium, while the expression of CSE appears to be induced in parietal cells by damage agents such as ethanol.

Anti-inflammatory and Gastroprotective Properties of Hypericum Richeri Oil Extracts

Oil extracts of flowering tops of Hypericum richeri Vill. prepared in three different ways were evaluated for chemical composition, and Anti-inflammatory and Gastroprotective activities. An HPLC method was developed for determination of two dominant flavonoids, quercetin and I3,II8-biapigenin. The carrageenan-induced rat paw edema test was used for screening the antiinflammatory activity, while indomethacin-induced rat gastric mucosa damage test was used for evaluation of gastroprotective activity. The oil extract prepared by maceration with 96% ethanol, followed by extraction with sunflower oil by heating on a water bath, exhibited the highest antiinflammatory (38.4 %) and gastroprotective activities (gastric damage score of 0.9). The same oil extract had the highest content of quercetin (49 μg/mL) and I3,II8-biapigenin (60 μg/mL). These results approve the usage of oil extracts of H. richeri as an antiinflammatory and gastroprotective agent.