Circadian time structure of circulating plasma lipid peroxides, antioxidant enzymes and other small molecules in peptic ulcers.

BACKGROUND: The circadian rhythm, as part of a broad time structure (chronome) of lipid peroxides and antioxidant defense mechanisms may relate to prevention, efficacy and management of preventive and curative chronotherapy. METHODS: Fifty newly diagnosed patients with peptic ulcers, 30-45 years of age, and 60 age-matched clinically healthy volunteers were synchronized for one week with diurnal activity from about 06:00 to about 22:00 and nocturnal rest. Breakfast was served around 08:30, lunch around 13:30 and dinner around 20:30. Drugs known to affect the free-radical systems were not taken. Blood samples were collected at 6-hour intervals for 24h under standardized, presumably 24-hour synchronized conditions. Plasma lipid peroxides, in the form of malondialdehyde (MDA), blood superoxide dismutase (SOD), glutathione peroxide (GPx), glutathione reductase (GR), catalase (CAT) activities, and serum total protein, albumin, ascorbic acid, total serum cholesterol, and HDL-cholesterol concentrations were determined. RESULTS: By population-mean cosinor analysis, a marked circadian variation was demonstrated for all variables in healthy subjects and in ulcer patients (p<0.001). As compared to controls, patients had a lower MESOR of MDA, SOD, GPx, GR, ascorbic acid, and HDL-C. They also had smaller circadian amplitude of SOD, CAT, GPx, GR, ascorbic acid, T-C, and HDL-C, but larger circadian amplitude of MDA and albumin. As compared to healthy subjects, the circadian acrophase of ulcer patients occurred later for MDA and GR and earlier for GPx. CONCLUSION: Mapping circadian rhythms, important chronome components that include trends with age and extra-circadian components characterizing antioxidants and pro-oxidants, is needed for exploring their putative role as markers in the treatment and management of peptic ulcers.

Gastroprotective effect of Neem (Azadirachta indica) bark extract: possible involvement of H(+)-K(+)-ATPase inhibition and scavenging of hydroxyl radical.

The antisecretory and antiulcer effects of aqueous extract of Neem (Azadirachta indica) bark have been studied along with its mechanism of action, standardisation and safety evaluation. The extract can dose dependently inhibit pylorus-ligation and drug (mercaptomethylimidazole)-induced acid secretion with ED(50) value of 2.7 and 2 mg Kg(-1) b.w. respectively. It is highly potent in dose-dependently blocking gastric ulcer induced by restraint-cold stress and indomethacin with ED(50) value of 1.5 and 1.25 mg Kg(-1) b.w. respectively. When compared, bark extract is equipotent to ranitidine but more potent than omeprazole in inhibiting pylorus-ligation induced acid secretion. In a stress ulcer model, it is more effective than ranitidine but almost equipotent to omeprazole. Bark extract inhibits H(+)-K(+)-ATPase activity in vitro in a concentration dependent manner similar to omeprazole. It offers gastroprotection against stress ulcer by significantly preventing adhered mucus and endogenous glutathione depletion. It prevents oxidative damage of the gastric mucosa by significantly blocking lipid peroxidation and by scavenging the endogenous hydroxyl radical ((z.rad;)OH)-the major causative factor for ulcer. The (z.rad;)OH-mediated oxidative damage of human gastric mucosal DNA is also protected by the extract in vitro. Bark extract is more effective than melatonin, vitamin E, desferrioxamine and alpha-phenyl N-tert butylnitrone, the known antioxidants having antiulcer effect. Standardisation of the bioactive extract by high pressure liquid chromatography indicates that peak 1 of the chromatogram coincides with the major bioactive compound, a phenolic glycoside, isolated from the extract. The pharmacological effects of the bark extract are attributed to a phenolic glycoside which is apparently homogeneous by HPLC and which represents 10% of the raw bark extract. A single dose of 1g of raw extract per kg b.w. (mice) given in one day and application of 0.6g raw extract per kg b.w. per day by oral route over 15 days to a cumulative dose of 9g per kg was well tolerated and was below the LD(50). It is also well tolerated by rats with no significant adverse effect. It is concluded that Neem bark extract has therapeutic potential for the control of gastric hyperacidity and ulcer.

[Prophylactic effects of a long-term therapy with vitamin A in stress ulcer? (author's transl)]. / Zur prophylaktischen Wirkung einer Langzeittherapie mit Vitamin A beim Stress-Ulkus

The possibility of a protective effect on the development of stress ulcers by increased vitamin A supplements was investigated in albino rats. No differences were found between vitamin A treated and control animals as regards frequency and size of the induced ulcers. Neither did vitamin A pre-treatment lead to increased staining of PAS-positive substances in the gastric mucosa. Measured activity of lysosomal enzymes in the gastric secretion was significantly higher for chitobiase and acid phosphatase in animals pretreated with 10,000 IU of vitamin A than in control animals.