No abstract

Treatment with small doses of topical capsaicin protects the gastric mucosa from the damage by strong irritants but functional ablation of sensory nerves by pretreatment with larger dose of parenteral capsaicin augments the formation of gastric lesions via unknown mechanism. This study was designed to determine the role of gastric acid secretion, mucosal blood flow (GBF) and prostaglandins (PG) generation in the gastroprotection induced by small doses of topical or parenteral capsaicin in rats with intact or capsaicin-deactivated sensory nerves. Gastric lesions were produced in rats with intact sensory nerves (series A) or capsaicin-deactivated nerves (series B) using intragastric (i.g.) application of 100% ethanol, acidified aspirin (ASA) or water immersion and restraint stress (WRS). Pretreatment with i.g. capsaicin (0.12-1.0 mg/kg) in rats with intact sensory nerves (series A) reduced dose-dependently the mucosal damage caused by ethanol, ASA or WRS, the dose inhibiting the lesion area by 50% (ID₅o) being 0.3, 0.5 and 0.7 mg/kg, respectively. This protection was accompanied by a significant rise in gastric mucosal blood flow (GBF). Parenteral application of capsaicin (1.2-10 mg/kg s.c.) that in intact rats dose-dependently increased GBF, also dose-dependently reduced gastric damage induced by ASA or WRS (but not by ethanol), the ID₅₀ being 5 and 3 mg/kg, respectively. The reduction by i.g. capsaicin of ethanol- or WRS-induced mucosal lesions was accompanied by a rise in GBF and this effect was reversed by indomethacin at a dose that suppressed endogenous PG biosynthesis by about 90%, indicating that PG are involved in the protective activities of topical capsaicin. Furthermore, topical and to a lesser extent parenteral capsaicin given to rats with intact or deactivated sensory nerves inhibited gastric acid and pepsin outputs, suggesting that this inhibition could contribute to the capsaicin-induced gastroprotection against acid-dependent mucosal lesions (ASA or WRS). Capsaicin deactiva-tion of sensory nerves aggravated mucosal lesions induced by all three ulcerogens and this effect was accompanied by a marked decrease in GBF. In such capsaicin-deactivated rats, topical capsaicin also reduced ethanol-, ASA- or WRS-induced lesions, while parenteral capsaicin was effective only in the protection against the damage induced by acidified ASA and WRS but not by ethanol. The protection against WRS lesions and accompanying rise in GBF by parenteral capsaicin were also reversed by the pretreatment with indomethacin applied in a dose suppressing the generation of PG. We conclude that capsaicin is capable of protecting gastric mucosa in rats with both intact and capsaicin-deactivated rats and that this protective activity depends, at least in part, upon its hyperemic and antisecretory effects that may be mediated, at least in part, by endogenous release of PG.

Capsaicin and papaverine are potent vasorelaxants with strong gastroprotective activity against damage induced by absolute ethanol. This protection was originally attributed to the increase in gastric mucosal blood flow (GBF) and the present study was designed to determine the possible role of nitric oxide (NO) and prostaglandins (PG) in the protective and hyperemic effects of capsaicin and papaverine on rat gastric mucosa. We found that the pretreatment with capsaicin (0.1-0.5 mg/kg i.g.) or papaverine (0.1-2 mg/kg i.g.) reduced dose dependently the area of ethanol-induced lesions, the ED₅₀ being 0.3 and 1 mg/kg, respectively. This protection was accompanied by a gradual increase in the GBF. Intravenous injection of N^ω-nitro-L-arginine (L -NNA; 1.2-5 mg/kg), a selective blocker of NO synthase, which by itself caused only a small increase in ethanol lesions, reversed dose dependently the protective and hyperemic effects of capsaicin and papaverine against ethanol-induced damage and attenuated the increase in GBF induced by each of these agents alone. This deleterious effect of L -NNA on the gastric mucosa and the GBF was fully antagonized by L -arginine (200 mg/kg i.v.) but not by D-arginine. L -arginine partly restored the decrease in GBF induced by L -NNA. Pretreatment with indomethacin (5 mg/kg i.p.), which suppressed the generation of PG by 85%, slightly enhanced the mucosal lesions induced by ethanol but failed to affect the fall in GBF induced by this irritant. Gastroprotective and hyperemic effects of capsaicin and papaverine were partly reversed by indomethacin suggesting that endogenous PG are also implicated in these effects. Addition of L -NNA to indomethacin completely eliminated both the protective and hyperemic effects of capsaicin and papaverine. We conclude that both NO and PG contribute to the gastroprotective and hyperemic effects of capsaicin and papaverine on the gastric mucosa.

Introduction Increased oxidative stress has been implicated in the pathogenesis of Crohn disease (CD). Except for C‑reactive protein (CRP), good biological markers of CD activity are lacking. Objectives We aimed to investigate the diagnostic usefulness of selected markers of oxidative stress in the serum and saliva of patients with active and inactive CD. Patients and methods A total of 58 patients with confirmed CD (32 with active CD, 26 with inactive CD, and 26 healthy controls) were prospectively enrolled to the study. The markers examined were malondialdehyde (MDA), ferric reducing ability of plasma (FRAP), reduced glutathione (GSH), and catalase (CAT). Results MDA levels were higher in the serum and saliva of patients with active CD than in those with inactive CD and controls and were positively correlated with the Crohn's Disease Activity Index (r = 0.8, P <0.001) and CRP (P <0.001). Serum and saliva antioxidant indicators (FRAP and GSH) were decreased in both CD groups compared with controls and were negatively correlated with clinical activity and inflammation (FRAP, r = -0.5, P <0.001; GSH, r = -0.5, P <0.001; and CAT, r = -0.5, P <0.001). Conclusions The increased lipid peroxidation and decreased antioxidant activity in serum and saliva confirm that CD patients are under oxidative stress. The positive correlations of MDA with the clinical activity and inflammation, as well as the comparison of the receiver operating characteristic curves for MDA and CRP, suggest that MDA could be a good diagnostic marker of CD.

IntroductIon Crohn's disease (CD) is a chronic granulomatous inflammatory disease of the entire gastrointestinal tract. Its etiology is unknown. The disease manifests itself with exacerbation (and then remission) of such symptoms as abdominal pain, fever, and weight loss, and is associated with many general and gastrointestinal complications. 1 Therapy involves the use of mesalazine and azathioprine. In active CD, corticosteroids and anti-tumor necrosis factor α (TNF-α) are introduced. 2,3 Since the first description of inflammatory lesions in the oral cavity of patients with CD, it has been well established that the mouth may be involved in the disease. 4 The prevalence of oral lesions is particularly common in children (48%-80%) compared with adults (0.5%-20%), but only a small proportion of lesions with granulomatous inflammation is characteristic of oral CD. 5-10 Nonspecific lesions, including aphthous stomatitis, ulcerations, and atrophic glossitis,