Increase In Thiobarbituric Acid Reactants Research Articles

Protective effect of rebamipide on indomethacin-induced intestinal damage in rats.

We evaluated the effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid), a novel anti-ulcer drug, on indomethacin-induced small intestinal lesions in rats. The animals were administered indomethacin (10 mg/kg, s.c.), and they were killed 24 h later. Rebamipide (30-300 mg/kg) was administered p.o. twice, 30 min before, and 6 h after indomethacin. Indomethacin caused hemorrhagic lesions in the rat small intestine, accompanied by an increase in enterobacterial translocation, inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) activities, as well as thiobarbituric acid (TBA) reactants, and these changes were significantly prevented by the supplementation with 16,16-dimethyl prostaglandin E2 (dmPGE2; 10 microg/kg, i.v.) or the pretreatment of animals with the antibiotic ampicillin. Treatment of the animals with rebamipide dose-dependently prevented the development of intestinal lesions, and this effect was mimicked by i.v. administration of superoxide dismutase (SOD: 3000 U/kg) + catalase (CAT: 5000 U/kg). The protection by rebamipide was accompanied by a significant suppression of the increase in both MPO and iNOS activities, and a complete inhibition of the increase in TBA reactants, while SOD + CAT significantly inhibited the increase of MPO activity and TBA reactants, but not iNOS activity. The bacterial translocation following indomethacin was also significantly decreased by either rebamipide or SOD + CAT. These results confirmed the importance of enterobacteria and iNOS/NO in the pathogenesis of indomethacin-induced small intestinal lesions, and suggested that rebamipide prevents the development of these lesions, probably by its radical scavenging action.

Plasma fatty acid status in Moroccan children: increased lipid peroxidation and impaired polyunsaturated fatty acid metabolism in protein-calorie malnutrition

In previous studies on plasma fatty acid and antioxidant status in 29 malnourished Moroccan children (12 with mild protein-calorie malnutrition, 17 with severe protein-calorie malnutrition) compared to 15 healthy control children from the same area, we pointed out that these populations were heterogeneous in terms of their essential fatty acid and antioxidant status. The aim of the present study was to classify the children using the Waterlow classification and their essential fatty acid status. The discrepancies in lipid parameters, nutritional and inflammatory markers, blood oxidative indexes, antioxidant micronutrients or trace elements (selenium, zinc, vitamin E) related to polyunsaturated fatty acids were checked in these populations. Eight of the control subjects and nine of the severe protein-calorie malnutrition children were essential fatty acid-deficient, compared to only one of the mild protein-calorie malnutrition group. Examination of the essential fatty acid-sufficient subjects with mild protein-calorie malnutrition, compared to the essential fatty acid-sufficient control subjects, showed only a decrease in Z scores and a non-significant decrease in selenium and vitamin E. In severely malnourished children, albumin, cholesterol and low density lipoprotein (LDL) cholesterol, plasma selenium, vitamin E and zinc were low, whereas inflammatory proteins and triglycerides were high. These features worsened with essential fatty acid deficiency. In all protein-calorie malnutrition subjects, there was oxidative stress (increase in thiobarbituric-acid reactants, imbalance between plasma polyunsaturated fatty acid, vitamin E and selenium levels), even in the absence of essential fatty acid deficiency. Monounsaturated fatty acids, oleic acid/stearic acid (C18:1 n-9/C18:0) Δ9 desaturase and n-3 and n-6 elongase activity indexes increased. The C18:1/C18:0 Δ9 desaturase activity index was negatively correlated to Z scores (r = –0.44, P < 0.01 for Z score weight, r = –0.39, P < 0.01 for Z score height), albumin (r = –0.82, P < 0.01) and zinc (r = –0.51, P < 0.01) levels. In essential fatty acid-deficient, severe protein-calorie malnutrition subjects, Δ6 desaturase activity was impaired, and there was a non-significant decrease in arachidonic acid. Essential fatty acid deficiency is a type of malnutrition, and is associated with an aggravation of all parameters in severe protein-calorie malnutrition. The increase in the C18:1/C18:0 Δ9 desaturase activity and enhanced lipid peroxidation without any essential fatty acid deficiency could be early markers of protein-calorie malnutrition.

Healing-Promoting Action of the Zinc-Cimetidine Complex on Acetic Acid-Induced Gastric Ulcers in Rats

We investigated the effect of the zinc-cimetidine complex on the healing of acetic acid-induced gastric ulcers in rats. When the effects of test drugs were assessed on the 15th day after acetic acid injection, the zinc-cimetidine complex at oral doses of 15.0 (11.4 mg as cimetidine), 30.0 and 60.0 mg/kg twice daily promoted the ulcer healing in a dose-dependent manner. Cimetidine was effective at oral doses of over 45.4 mg/kg twice daily. ZnCl2 was ineffective on all ulcer parameters. The effect of the combination of cimetidine and ZnCl2 was similar to that of cimetidine alone. The zinc-cimetidine complex had already inhibited the increase in thiobarbituric acid reactants in the ulcerated region before the ulcer-healing effect of this compound was recognized. A single oral administration of the complex at 15 and 30 mg/kg to normal rats was ineffective in inhibiting acid secretion and in increasing serum gastrin levels, although cimetidine was markedly effective on both parameters. These results indicate that the zinc-cimetidine complex at about 1 /4 the dose of cimetidine was as effective as cimetidine when the ulcer-healing effects of both compounds were compared with the same dose of cimetidine. In addition, the ulcer-healing effect of this complex may be due, at least in part, to the inhibition of lipid peroxidation but not due to the inhibition of acid secretion or the trophic effect of gastrin.

Lipid peroxidation in neonatal mouse brain subjected to two different types of hypoxia

To elucidate the role of free radicals in the pathogenesis of neonatal hypoxic encephalopathy, we determined the content of thiobarbituric acid reactants (TBARs), as an index of lipid peroxidation related with a free radical reaction, in the brains of newborn mice during hypoxia and recovery from hypoxia. Hypoxic stress was induced by 100% nitrogen gas breathing (N2 group) or 100% carbon dioxide gas breathing (CO2 group). TBARs increased with 20 minutes of hypoxia and returned to the control level during the recovery period in both groups. The increase in TBARs in the CO2 group was greater than that in the N2 group. These results may suggest that free radical reaction occurs during the hypoxic period and that CO2 hypoxia is more effective on free radical production in the newborn brain than N2 hypoxia.

Role of oxygen radicals in the pathogenesis of gastric mucosal lesions induced by water-immersion restraint stress and burn stress in rats.

The formation of gastric mucosal lesions and the increase in thiobarbituric acid (TBA)-reactive substances induced by water-immersion restraint stress or burn stress in rats were significantly inhibited by the treatment with superoxide dismutase (SOD) and/or catalase. Allopurinol inhibited the formation of gastric mucosal injury induced by burn stress, but not the increase in TBA reactants. A drop in the polymorphonuclear leukocyte (PMN) count induced by an injection of anti-rat PMN antibody did not inhibit the aggravation of gastric mucosal lesions or the increase in TBA reactants in either of the stress models. These results suggest that active oxygen species and lipid peroxidation may play a role in the formation of gastric mucosal damage induced by stress. Reduced microcirculation of the gastric mucosa induced by water-immersion restraint or burn stress did not change following treatment with SOD and/or catalase, suggesting that the effectiveness of SOD and catalase on the gastric mucosal lesions induced by stress may occur via the scavenging of oxygen radicals, and not through an effect on gastric mucosal microcirculation.

Selenium modulates peroxidation in the absence of glutathione peroxidase in Musca domestica

Adult houseflies fed a low-selenium diet showed a 73% decrease in total Se compared to those given 1.0 ppm Se in their drinking water. This decrease was associated with a 84.4% increase in thiobarbituric acid reactants and a 16.3% increase in conjugated dienes. These increases were unrelated to activities of glutathione S-transferases, superoxide dismutases and catalase and to levels of reduced and oxidized glutathione, all of which were unaltered by Se deficiency. Since houseflies lack glutathione peroxidase, Se apparently modulates peroxidation in these animals independent of the antioxidant enzymes and glutathione.

Role of oxygen-derived free radicals in gastric mucosal injury induced by ischemia or ischemia-reperfusion in rats.

Oxygen-derived free radicals have been implicated as possible mediators in the development of tissue injury induced by ischemia and reperfusion. Clamping of the celiac artery in rats reduced the gastric mucosal blood flow to 10% of that measured before the clamping. The area of gastric erosions and thiobarbituric acid (TBA) reactants in gastric mucosa were significantly increased 60 and 90 min after clamping. These changes were inhibited by treatment with SOD and catalase. Thirty and 60 min after reoxygenation. produced by removal of the clamps following 30 min of ischemia, gastric mucosal injury and the increase in TBA reactants were markedly aggravated compared with those induced by ischemia alone. SOD and catalase significantly inhibited these changes. The serum alpha-tocopherol/cholesterol ratio, an index of in vivo lipid peroxidation, was significantly decreased after long periods of ischemia (60 and 90 min), or after 30 and 60 min of reperfusion following 30 min of ischemia. These results indicated that active oxygen species and lipid peroxidation may play a role in the pathogenesis of gastric mucosal injury induced by both ischemia alone and ischemia-reperfusion. Although, allopurinol inhibited the formation of gastric mucosal injury and the increase in TBA reactants in gastric mucosa, the depletion of polymorphonuclear leukocytes (PMN) counts induced by an injection of anti-rat PMN antibody did not inhibit these changes. As compared with the hypoxanthine-xanthine oxidase system. PMN seem to play a relatively small part in the formation of gastric mucosal injury induced by ischemia-reperfusion.

Effect of zinc-carnosine chelate compound (Z-103) on burn-induced gastric mucosal injury in rats.

The protective effect of a novel synthetic zinc-carnosine chelate compound, zinc N-(3-aminopropionyl)-L-histidine (Z-103), on the gastric injury induced by burn stress was studied in rats. Gastric lesions were produced by immersion of half of the animal's body into 80°C water for 10s. The increase in total area of the erosions 3h after the stress and the increase in thiobarbituric acid reactants in the gastric mucosa were significantly inhibited by the administration of Z-103 at doses of 30, 100, and 300mg/kg. The decrease in blood flow in the gastric mucosa was not influenced by the treatment with Z-103. These results suggest that the protective effect of Z-103 against the aggravation of burn-induced gastric mucosal injury may be due to its inhibitory effect on lipid peroxidation.

Role of Lipid Peroxidation and Oxygen Radicals in Compound 48/80-Induced Gastric Mucosal Injury in Rats

Repeated administration of a small dose of compound 48/80 induced acute gastric mucosal injury in rats. Thiobarbituric acid (TBA) reactants in the gastric mucosa were significantly increased and serum alpha-tocopherol was significantly decreased after the treatment. The total area of gastric lesions and the increase in TBA reactants in the gastric mucosa were significantly reduced by pretreatment with superoxide dismutase (SOD) and/or catalase, allopurinol and anti-rat polymorphonuclear leukocytes (PMN) antibody. Lipid peroxidation and oxygen radicals derived from both the xanthine-xanthine oxidase system and PMN may be involved in the pathogenesis of compound 48/80-induced gastric mucosal injury.