Noboru Harada

Inhibitory effect of green tea catechins in combination with sucralfate on Helicobacter pylori infection in Mongolian gerbils

BackgroundThe occurrence of antibiotic-resistant Helicobacter pylori has been reported. It is desirable to develop an effective method to prevent the occurrence of resistant strains of Helicobacter pylori. Green tea catechins (GTCs) have been reported to have an antibacterial effect. Therefore, the possibility of eradicating Helicobacter pylori by the oral administration of GTCs was investigated.MethodsSolutions of GTCs and solutions of GTCs adsorbed to sucralfate (GTC-scf), at concentrations of 20 mg GTCs and/or 20 mg sucralfate/ml were prepared. Then 1 ml of the GTC-scf or the GTC solution was administered daily, for 10 days to Mongolian gerbils infected with Helicobacter pylori. Then the stomachs were extirpated and homogenized. The homogenate was spread on selective medium plates. After 5-day culture, colony-forming units (CFU) of Helicobacter pylori were counted.ResultsThe CFU of Helicobacter pylori was significantly decreased by GTC-scf.ConclusionsGTC-scf may have a bactericidal effect on Helicobacter pylori infection.

Effect of green tea catechins on the amount of 8-hydroxydeoxyguanosine (8-OHdG) in pancreatic and hepatic DNA after a single administration of N-nitrosobis(2-oxopropyl)amine (BOP).

Effects of green tea catechins on N-nitrosobis(2-oxopropyl)amine (BOP)-induced oxidative stress in pancreas and liver were examined. Hamsters were divided into two groups: one group was given free access to a 0.1% solution of green tea catechins as drinking water (c-ham) and the other to plain tap water (w-ham) for 1 week before subcutaneous injection of BOP 20 mg/kg body weight. Zero, 1, 2, 6, 12, 24, and 48 h after BOP injection, the pancreas and liver were excised and the tissue concentration of lipid peroxides (TBA values) and the amount of 8-hydroxydeoxyguanosine (8-OHdG) in nuclear DNA were measured. The concentration of lipid peroxides and the amount of 8-OHdG in the pancreas showed similar patterns of change between c-and w-ham. Soon after BOP injection, the concentration of lipid peroxides and the amount of 8-OHdG increased with a peak at 1 and 6 h, respectively. Their peak values of c-ham were significantly depressed compared with those of w-ham. Both levels returned to steady-state levels by 24 h. In the liver, the concentration of lipid peroxides and the amount of 8-OHdG were not affected by BOP administration. These results suggest that BOP induces oxidative damages in the target organ and oral intake of green tea catechins has a protective effect on the oxidative stress.

Effects of green tea catechins (Polyphenon 100) on cerulein-induced acute pancreatitis in rats.

Effects of green tea catechins (GTC) on cerulein-induced acute pancreatitis in rats were examined. The acute pancreatitis induced by cerulein (cerulein pancreatitis) was characterized by interstitial edema and vacuolation. When cerulein pancreatitis was induced, prior administration of 0.1% GTC in drinking water for 1 week before the induction significantly decreased the wet weight of the pancreas, the serum level of amylase, and the tissue concentration of lipid peroxides in the pancreas compared with those in nonmedicated rats supplied with plain tap water only. Furthermore, the pancreatic tissue alterations of the medicated rats were milder than those of the nonmedicated rats. These data suggest that GTC have a protective effect on the pathogenesis of cerulein pancreatitis.

Accumulation of 8-Oxo-2’-Deoxyguanosine (as a Biomarker of Oxidative DNA Damage) in the Tissues of Aged Hamsters and Change in Antioxidant Enzyme Activities after Single Administration of N-Nitrosobis(2-Oxopropyl) Amine

Background: It has been reported that DNA oxidative damage accumulates with age. Two reasons for this phenomenon are the decline in the antioxidant system and the decline in the repair system. It is not clear which of these is the main reason. Objective: To study whether the decline in antioxidant enzyme activities causes the accumulation of DNA oxidative damage, an experimental study was performed with hamsters. Methods: Seventy-four female Syrian golden hamsters were divided into 2 groups: a young group (28 hamsters), and an aged group (46 hamsters). The hamsters in the aged group were kept in our laboratory until they were 18 months old. The levels of 8-oxo-2′-deoxyguanosine (8-oxodG) and the activities of antioxidant enzymes, i.e. catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx), were measured in both groups. Furthermore, the same parameters were measured in the pancreas and liver following administration of N-nitrosobis(2-oxopropyl)amine (BOP), an inducer of oxidative stress in the hamster pancreas. Results: In the mid brain, cerebellum, lung, heart, spleen and kidney, the 8-oxodG contents in aged hamsters were significantly higher than those in young hamsters. GPx activity decreased with age in the lung, liver and kidney, whereas SOD activity increased in the lung and liver but decreased in the kidney of aged animals. Catalase activity increased in the cerebrum, heart, pancreas and kidney but decreased in the lung and spleen of aged hamsters. When the pancreatic levels of 8-oxodG and antioxidant enzymes were measured after BOP administration, there was no clear-cut relation between the changes in those levels. Conclusions: From these results the increase in 8-oxodG contents in aged hamsters does not seem to be related to the antioxidant system but rather to a possible decline in the repair system against oxidative damage.

The effects of green tea catechins (polyphenon) on DL-ethionine-induced acute pancreatitis

The effects of green tea catechins (Polyphenon) on dl-ethionine-induced acute pancreatitis in rats were examined. The acute pancreatitis induced in this study was characterized by moderate inter- and intrastitial edema and patchy acinar cell necrosis. In rats induced with acute pancreatitis by an intraperitoneal injection of dl-ethionine, the wet weight of the pancreas (0.47±0.059 g/100 g body weight; p < 0.05), the serum amylase (10,432±996 IU/L; p < 0.001), and the tissue concentration of lipid peroxides (19.5±1.78 nmol/mg tissue DNA; p < 0.001) were significantly increased compared with values obtained in control rats (0.39±0.037 g/100 g body weight, 5,639±1,568 IU/L, and 10.7±1.04 nmol/mg tissue DNA, respectively) injected with isotonic saline. In contrast, in rats injected with dl-ethionine and supplied with a green tea catechin solution as a beverage instead of water during the experimental period, the tissue of pancreas was almost-correct, and the wet weight of the pancreas (0.39±0.054 g/100 g body weight; p < 0.05), the serum amylase (5,716±708 IU/L; p < 0.001), and the concentration of lipid peroxides in tissue (11.5±2.15 nmol/mg tissue DNA; p < 0.001) were significantly decreased compared with values obtained in rats injected with dl-ethionine and supplied with water as a beverage. These data suggest that green tea catechins may have a protective effect on the pathogenesis of experimental acute pancreatitis.

Suppression of 8-oxo-2'-deoxyguanosine formation and carcinogenesis induced by N-nitrosobis (2-oxopropyl)amine in hamsters by esculetin and esculin

Effects of esculetin (6,7-dihydroxycoumarin) and its glycoside, esculin, on 8-oxo-2′-deoxyguanosine (8-oxodG) formation and carcinogenesis induced by a chemical carcinogen, N-nitrosobis(2-oxopropyl)amine (BOP), were examined in the pancreas of female Syrian golden hamsters. Animals were administered esculetin by gastric intubation into the stomach 30 min before BOP administration or ingestion of a diet containing esculin for 7 days before BOP administration, and killed 1 or 4 h after BOP treatment, and the contents of thiobarbituric acid-reacting substrates (TBARS) and 8-oxodG in the pancreas were determined. Both compounds suppressed significantly the BOP-induced increases in 8-oxodG and TBARS contents in hamster pancreas. We further investigated the effect of esculin on pancreatic carcinogenesis by the rapid production model induced by augmentation pressure with a choline-deficient diet, ethionine, methionine and BOP. Esculin was given ad libitum as a 0.05% aqueous solution in either the initiation or promotion phases. The incidence of invasive tumors in animals given esculin during the initiation phase was significantly smaller than in the control group, while esculin given during the promotion phase showed no apparent effects. These results suggest that the intake of esculin has an inhibitory effect on BOP-induced oxidative DNA damage and carcinogenesis in hamster pancreas.

Effect of black tea aqueous non-dialysate onHelicobacter pylori infection in Mongolian gerbils.

ObjectivesRecently, the appearance ofHelicobacter pylori (H. pylori) resistant to antibiotics has been reported. The development of an antibiotic therapy which would not induce resistant strains ofH. pylori is anticipated. In the present study, the antibiotic effect of black tea aqueous non-dialysate (BTND), the fraction different from tea catechins, onH. pylori was investigated using Mongolian gerbils infected withH. pylori.MethodsBTND was extracted from black tea leaves. A 0.1 w/v% solution of BTND or green tea catechins (GTC) was provided as drinking water to male NGS/Sea Mongolian gerbils infected withH. pylori (ATCC43504) for two weeks. Their stomachs were then excised, the mucosal surfaces were macroscopically observed, and colony forming units (CFU) ofH. pylori were counted. The data were compared between the BTND and GTC groups.ResultsThe CFU ofH. pylori were significantly decreased by intake of BTND. The body weight of the animals tended to be larger in the group supplied with BTND than in that supplied with GTC. Gastric mucosal injury tended to be smaller in the animals supplied with BTND than in those with GTC.ConclusionsThese results suggest that BTND may have an inhibitory effect onH. pylori infection.