Yoshiji Ohta

The preventive effect of teprenone (6,10,14,18-teramethyl-5,9,13,17-nonadecatetaene-2-one), an anti-ulcer drug, on acute gastric mucosal lesion progression was examined in rats with a single intraperitoneal (i.p.) injection of compound 48/80 (0.75 mg/kg). Teprenone (20, 100 or 200 mg/kg), which was orally administered 0.5 h after compound 48/80 treatment at which time gastric mucosal lesions appeared, prevented gastric mucosal lesion development at 3 h after the treatment dose-dependently. Gastric mucosal tissues of compound 48/80-treated rats showed increases in myeloperoxidase (an index of neutrophil infiltration) and xanthine oxidase activities and thiobarbituric acid reactive substances (an index of lipid peroxidation) content and decreases in Se-glutathione peroxidase activity and hexosamine and vitamin E contents at 3 h after the treatment. Post-administered teprenone attenuated all these changes dose-dependently. These results indicate that teprenone prevents acute gastric mucosal lesion progression in compound 48/80-treated rats possibly by suppressing gastric mucus depletion, neutrophil infiltration and oxidative stress in the gastric mucosal tissue. (C) 2004 Elsevier B.V. All rights reserved.

The preventive effect of teprenone (6,10,14,18-teramethyl-5,9,13,17-nonadecatetaene-2-one), an anti-ulcer drug, on acute gastric mucosal lesion progression was examined in rats with a single intraperitoneal (i.p.) injection of compound 48/80 (0.75 mg/kg). Teprenone (20, 100 or 200 mg/kg), which was orally administered 0.5 h after compound 48/80 treatment at which time gastric mucosal lesions appeared, prevented gastric mucosal lesion development at 3 h after the treatment dose-dependently. Gastric mucosal tissues of compound 48/80-treated rats showed increases in myeloperoxidase (an index of neutrophil infiltration) and xanthine oxidase activities and thiobarbituric acid reactive substances (an index of lipid peroxidation) content and decreases in Se-glutathione peroxidase activity and hexosamine and vitamin E contents at 3 h after the treatment. Post-administered teprenone attenuated all these changes dose-dependently. These results indicate that teprenone prevents acute gastric mucosal lesion progression in compound 48/80-treated rats possibly by suppressing gastric mucus depletion, neutrophil infiltration and oxidative stress in the gastric mucosal tissue. (C) 2004 Elsevier B.V. All rights reserved.

We examined whether short-term ascorbic acid deficiency induces oxidative stress in the retinas of young guinea pigs. Four-week-old guinea pigs were given a scorbutic diet (20 g/animal/day) with and without adequate ascorbic acid (400 mg/animal/day) in drinking water for 3 weeks. The serum concentrations of the reduced form of ascorbic acid and the oxidized form of ascorbic acid in the deficient group were 14.1 and 4.1%, respectively, of those in the adequate group. The retinal contents of the reduced form of ascorbic acid and the oxidized form of ascorbic acid in the deficient group were 6.4 and 27.3%, respectively, of those in the adequate group. The retinal content of thiobarbituric acid-reactive substances, an index of lipid peroxidation, was 1.9-fold higher in the deficient group than in the adequate group. Retinal reduced glutathione and vitamin E contents in the deficient group were 70.1 and 69.4%, respectively, of those in the adequate group. This ascorbic acid deficiency did not affect serum thiobarbituric acid-reactive substances and reduced glutathione concentrations but increased serum vitamin E concentration. These results indicate that short-term ascorbic acid deficiency induces oxidative stress in the retinas of young guinea pigs without disrupting systemic antioxidant status. Copyright (C) 2004 National Science Council, ROC and S. Karger AG, Basel.

We examined whether short-term ascorbic acid deficiency induces oxidative stress in the retinas of young guinea pigs. Four-week-old guinea pigs were given a scorbutic diet (20 g/animal/day) with and without adequate ascorbic acid (400 mg/animal/day) in drinking water for 3 weeks. The serum concentrations of the reduced form of ascorbic acid and the oxidized form of ascorbic acid in the deficient group were 14.1 and 4.1%, respectively, of those in the adequate group. The retinal contents of the reduced form of ascorbic acid and the oxidized form of ascorbic acid in the deficient group were 6.4 and 27.3%, respectively, of those in the adequate group. The retinal content of thiobarbituric acid-reactive substances, an index of lipid peroxidation, was 1.9-fold higher in the deficient group than in the adequate group. Retinal reduced glutathione and vitamin E contents in the deficient group were 70.1 and 69.4%, respectively, of those in the adequate group. This ascorbic acid deficiency did not affect serum thiobarbituric acid-reactive substances and reduced glutathione concentrations but increased serum vitamin E concentration. These results indicate that short-term ascorbic acid deficiency induces oxidative stress in the retinas of young guinea pigs without disrupting systemic antioxidant status. Copyright (C) 2004 National Science Council, ROC and S. Karger AG, Basel.

Omeprazole, a proton pump inhibitor is known to function not only as a proton pump inhibitor but also as an anti-inflammatory agent, an antioxidant or a stimulator of gastric mucus secretion. We have shown that the pathogenesis of acute gastric mucosal lesions induced by compound 48/80, a mast cell degranulator, in rats involves neutrophil infiltration, lipid peroxidation, and mucin depletion, but not acid secretion, in the gastric mucosal tissue. Therefore, we examined whether omeprazole protects against acute gastric mucosal lesions induced by compound 48/80 in rats. Rats were injected with omeprazole (10 or 50 mg kg(-1), i.p.) at 0.5 h before injection of compound 48/80 (0.75 mg kg(-1), i.p.). Omeprazole prevented gastric mucosal lesion development at 0.5 and 3 h after compound 48/80 injection. Omeprazole attenuated decreased nonprotein sulfhydryl content and increased myeloperoxidase and xanthine oxidase (XO) activities and lipid peroxide (LPO) content in the gastric mucosa at 0.5 h after compound 48/80 injection and increased myeloperoxidase and XO activities and LPO content, but not decreased hexosamine and adherent mucus contents, in the gastric mucosa at 3 h. These results indicate that omeprazole protects against compound 48/80-induced acute gastric mucosal lesions in rats possibly through its anti-inflammatory and antioxidant actions. (C) 2002 Elsevier Science Ltd. All rights reserved.

Omeprazole, a proton pump inhibitor is known to function not only as a proton pump inhibitor but also as an anti-inflammatory agent, an antioxidant or a stimulator of gastric mucus secretion. We have shown that the pathogenesis of acute gastric mucosal lesions induced by compound 48/80, a mast cell degranulator, in rats involves neutrophil infiltration, lipid peroxidation, and mucin depletion, but not acid secretion, in the gastric mucosal tissue. Therefore, we examined whether omeprazole protects against acute gastric mucosal lesions induced by compound 48/80 in rats. Rats were injected with omeprazole (10 or 50 mg kg(-1), i.p.) at 0.5 h before injection of compound 48/80 (0.75 mg kg(-1), i.p.). Omeprazole prevented gastric mucosal lesion development at 0.5 and 3 h after compound 48/80 injection. Omeprazole attenuated decreased nonprotein sulfhydryl content and increased myeloperoxidase and xanthine oxidase (XO) activities and lipid peroxide (LPO) content in the gastric mucosa at 0.5 h after compound 48/80 injection and increased myeloperoxidase and XO activities and LPO content, but not decreased hexosamine and adherent mucus contents, in the gastric mucosa at 3 h. These results indicate that omeprazole protects against compound 48/80-induced acute gastric mucosal lesions in rats possibly through its anti-inflammatory and antioxidant actions. (C) 2002 Elsevier Science Ltd. All rights reserved.

The antilipid peroxidative action of the ethanol extract of Brazilian propolis at a concentration of 47% (w/v) was evaluated by examining the inhibitory effect of the extract on the formation of hydroperoxide- and endoperoxide-type lipid peroxides during heating of authentic polyunsaturated fatty acids and on Fe3+-ADP/ascorbic acid- and Fe3+-ADP/NADPH-dependent lipid peroxidation reactions in rat liver microsomes. Hydroperoxide-type lipid peroxides were measured by the haemoglobin-methylene blue method and endoperoxide-type lipid peroxides by the thiobarbituric aicd (TBA), Fe3+-TBA and LPO-586 methods. Propolis ethanol extract inhibited dose-dependently the formation of hydroperoxide- and endoperoxide-type lipid peroxides during heating of linoleic acid, linolenic acid or arachidonic acid and the amount of the extract causing a half inhibition of these lipid peroxide formations ranged between 20 and 75 mug. Propolis ethanol extract inhibited dose-dependently both Fe3+-ADP/ascorbic acid- and Fe3+- ADP/NADPH-dependent lipid peroxidation reactions in rat liver microsomes when lipid peroxides produced in both reactions were measured by the TBA method. The amount of propolis extract causing a half inhibition of the Fe3+-ADP/ascorbic acid-dependent lipid peroxidation was about 5 mug, while that of the extract causing a half inhibition of the Fe3+-ADP/NADPH-dependent lipid peroxidation was about 0.15 mug. These results indicate that the propolis ethanol extract exerts an antilipid peroxidative action at very low doses. Copyright (C), 2002 John Wiley Sons, Ltd.

Pretreatment with L-arginine (150-600 mg kg(-1), i.p.), but not D-arginine (600 mg kg(-1), i.p.), protected against gastric mucosal lesions in rats with water immersion restraint stress over a 6-h period. This protective effect occurred in a dose-dependent manner. Increases in the activities of inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO), an index of tissue neutrophil infiltration, and the concentration of nitrite/nitrate, breakdown products of nitric oxide, and a decrease in the activity of constitutive nitric oxide synthase (cNOS) occurred in the gastric mucosal tissue with the development of gastric mucosal lesions. The L-arginine pretreatment attenuated the increases in iNOS and MPO activities and nitrite/nitrate concentration and the decrease in cNOS activity in the gastric mucosal tissue in a dose-dependent manner, while the D-arginine pretreatment did not. Both the protective effect of L-arginine (300 mg kg(-1)) against stress-induced gastric mucosal lesions and the attenuating effect of the amino acid on the increases in gastric mucosal iNOS and MPO activities and the decrease in gastric mucosal cNOS activity with the lesion development were counteracted by pretreatment with NG-monomethyl-L-arginine (100 mg kg(-1), s.c.), a nitric oxide synthase inhibitor, but not its D-isomer (100 mg kg(-1), s.c.). These results suggest that the protective effect of exogenously administered L-arginine against stress-induced gastric mucosal lesions in rats is, at least in part, due to nitric oxide-mediated inhibition of neutrophil infiltration into the gastric mucosal tissue. (C) 2001 Academic Press.

Pretreatment with L-arginine (150-600 mg kg(-1), i.p.), but not D-arginine (600 mg kg(-1), i.p.), protected against gastric mucosal lesions in rats with water immersion restraint stress over a 6-h period. This protective effect occurred in a dose-dependent manner. Increases in the activities of inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO), an index of tissue neutrophil infiltration, and the concentration of nitrite/nitrate, breakdown products of nitric oxide, and a decrease in the activity of constitutive nitric oxide synthase (cNOS) occurred in the gastric mucosal tissue with the development of gastric mucosal lesions. The L-arginine pretreatment attenuated the increases in iNOS and MPO activities and nitrite/nitrate concentration and the decrease in cNOS activity in the gastric mucosal tissue in a dose-dependent manner, while the D-arginine pretreatment did not. Both the protective effect of L-arginine (300 mg kg(-1)) against stress-induced gastric mucosal lesions and the attenuating effect of the amino acid on the increases in gastric mucosal iNOS and MPO activities and the decrease in gastric mucosal cNOS activity with the lesion development were counteracted by pretreatment with NG-monomethyl-L-arginine (100 mg kg(-1), s.c.), a nitric oxide synthase inhibitor, but not its D-isomer (100 mg kg(-1), s.c.). These results suggest that the protective effect of exogenously administered L-arginine against stress-induced gastric mucosal lesions in rats is, at least in part, due to nitric oxide-mediated inhibition of neutrophil infiltration into the gastric mucosal tissue. (C) 2001 Academic Press.

Teprenone, an anti-ulcer drug, has been reported to promote the healing of acetic acid-induced chronic gastric ulcers in rats by stimulating gastric mucus synthesis and secretion. Recently, it has been implicated that neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues have an inhibitory effect on the healing of acetic acid-induced chronic gastric ulcers in rats. Therefore, we attempted to clarify whether teprenone exerts a healing-promoting effect on acetic acid-induced chronic gastric ulcers through its inhibitory effect on neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues. In rats with chronic gastric ulcers made by applying acetic acid to the stomach, gastric ulcer healing started later than 3 days after the acetic acid application. Gastric mucosal myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration, and lipid peroxide content were higher in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application. Gastric mucosal non-protein SH content was lower in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application, and gastric mucosal adherent mucus content was lower in the ulcerated region than in the intact region on the 8th and 15th day. Daily oral administration of teprenone (100 mg kg(-1) x 2) for 7 or 14 days, starting on the 8th day after the application of acetic acid to the stomach, enhanced the reduction of the ulcer area with attenuation of all these biochemical changes found in the ulcerated region. The teprenone administration caused a decrease in MPO activity and an increase in adherent mucus content in the gastric mucosa of the intact region. These results suggest that the healing-promoting effect of teprenone on acetic acid-induced chronic gastric ulcers in rats could be due not only to stimulation of gastric mucus secretion but also to inhibition of neutrophil infiltration and enhanced lipid peroxidation in the ulcerated gastric tissue. (C) 2001 Academic Press.