Screening of cardioprotective diseases bioactive components from Danshen extracts and LC-MS analysis.

A rapid and efficient analysis and screening method is adopted for cell affinity capture coupled with HPLC-MS (CAC-HPLC-MS) analysis of bioactive components that have possible efficiency against cardiovascular diseases. This method involves affinity capture, concentration, and separation of bioactive components from Danshen library using oxidatively damaged endothelial cells induced by H2 O2 , as well as analysis and identification of targeted compounds with HPLC and MS. It combines the specific interaction between cell membrane receptors and bioactive components with the powerful analysis and identification function of HPLC-MS. The CAC-HPLC-MS method was also used for analysis and screening of bioactive components from crude extracts of Danshen. A total of 19 components were found to be bound to oxidatively damaged endothelial cells with seven of these identified. Existing literature confirms that these seven components have many activities related to cardioprotective diseases. Therefore, the combination of biological affinity capture with HPLC-MS should be regarded as an attractive method with great potential for rapid and efficient screening of bioactive components related to anti-cardiovascular diseases from natural product libraries.

Association of dietary fat and carbohydrate consumption and predicted ten-year risk for developing coronary heart disease in a general Japanese population.

We examined the relationships between dietary carbohydrate, protein, fat, and the ratio of n6/n3 fatty acid intakes with the predicted 10-year coronary heart disease (CHD) risk in a general Japanese population. We used the Framingham risk score to determine the 10-year CHD risk of the subjects, who were employees of 6 companies in a single prefecture in Japan. After excluding the subjects who reported any history of angina pectoris, myocardial infarction, diabetes, or cancer, and those with missing data resulting in the inability of estimation of 10-year CHD risk and food intakes, the final data analysis was carried out for 809 subjects. The logistic regression models revealed a significantly increased odds ratio of 10-year CHD risk in the subjects with the highest tertile of carbohydrate intake (% energy) (odds ratio 3.64, 95% CI, 2.07-6.40); after adjustment for other variables, the odds ratio for the 10-year CHD risk was also higher in the subjects with the highest tertile of carbohydrate intake (odds ratio 1.72, 95% CI, 0.70-4.25). We also found that fat intake and the ratio of n6/n3 fatty acids were inversely associated with the predicted 10-year CHD risk (p for trend<0.01). The present findings added evidence of a positive association of dietary carbohydrate and inverse associations of total fat and n6/n3 fatty acid ratio with the predicted 10-year CHD risk in a general Japanese population.

Relationship between ceruloplasmin and oxidative biomarkers including ferritin among healthy Japanese.

Serum ceruloplasmin (CP), a marker relevant to copper metabolism, is one of famous inflammation markers with a reduction in Wilson's disease, whereas serum ferritin is a marker relevant to iron metabolism. Recently, ferritin is pointed out to be related with oxidative stress. However, there is still no population research which showed the relation of CP and ferritin. Therefore, we investigated the relationship between CP and ferritin including oxidative stress biomarkers among healthy Japanese (n = 389). We measured serum CP, ferritin, Fe, high-sensitivity C-reactive protein (hs-CRP), and urinary oxidative stress biomarkers [H2O2, 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-isoprostane] and so on. Subjects showed that age; 41.7 ± 10.0 (year), CP; 31.9 ± 6.8 (mg/dl), ferritin; 123.5 ± 121.0 (ng/ml), hs-CRP; 0.89 ± 2.53 (mg/l), 8-OHdG; 10.2 ± 4.4 [ng/mg creatinine (Cre)] and H2O2; 6.5 ± 10.9 (µM/g Cre), (All data mentioned above were expressed as mean ± SD). CP was significantly and positively correlated with hs-CRP and inversely correlated with ferritin, Fe and 8-OHdG. By a multiple logistic regression analysis, odds ratio of CP according to quartiles of hs-CRP was 4.86, and according to quartiles of 8-OHdG was 0.39 after adjusting for age and other confounding factors. In conclusion, our findings suggest that CP was an antioxidative biomarker which controls oxidative stress, whereas ferritin was a marker which may participate in the generation of oxidative stress.

Acatalasemic mice are mildly susceptible to adriamycin nephropathy and exhibit increased albuminuria and glomerulosclerosis.

BACKGROUND: Catalase is an important antioxidant enzyme that regulates the level of intracellular hydrogen peroxide and hydroxyl radicals. The effects of catalase deficiency on albuminuria and progressive glomerulosclerosis have not yet been fully elucidated. The adriamycin (ADR) nephropathy model is considered to be an experimental model of focal segmental glomerulosclerosis. A functional catalase deficiency was hypothesized to exacerbate albuminuria and the progression of glomerulosclerosis in this model. METHODS: ADR was intravenously administered to both homozygous acatalasemic mutant mice (C3H/AnLCs(b)Cs(b)) and control wild-type mice (C3H/AnLCs(a)Cs(a)). The functional and morphological alterations of the kidneys, including albuminuria, renal function, podocytic, glomerular and tubulointerstitial injuries, and the activities of catalase were then compared between the two groups up to 8 weeks after disease induction. Moreover, the presence of a mutation of the toll-like receptor 4 (tlr4) gene, which was previously reported in the C3H/HeJ strain, was investigated in both groups. RESULTS: The ADR-treated mice developed significant albuminuria and glomerulosclerosis, and the degree of these conditions in the ADR-treated acatalasemic mice was higher than that in the wild-type mice. ADR induced progressive renal fibrosis, renal atrophy and lipid peroxide accumulation only in the acatalasemic mice. In addition, the level of catalase activity was significantly lower in the kidneys of the acatalasemic mice than in the wild-type mice during the experimental period. The catalase activity increased after ADR injection in wild-type mice, but the acatalasemic mice did not have the ability to increase their catalase activity under oxidative stress. The C3H/AnL strain was found to be negative for the tlr4 gene mutation. CONCLUSIONS: These data indicate that catalase deficiency plays an important role in the progression of renal injury in the ADR nephropathy model.

Relation of prenatal and postnatal status to calcaneus quantitative ultrasound in adolescents.

This study aimed to elucidate the relationship of prenatal and/or postnatal factors, including acquired factors, with the calcaneus stiffness index as measured by quantitative ultrasound (QUS-SI) in adolescents. We recruited 1,143 adolescents with a mean age of 14.8 ± 1.8 years (501 boys and 642 girls). The subjects' calcaneus QUS-SI was measured using an ultrasound bone densitometer. We also measured the subjects' height, weight, and grip strength. Data on prenatal and postnatal factors were obtained from maternal and child health handbooks. A self-reporting questionnaire was used to obtain information on subjects' secondary sexual characteristics and lifestyle factors. We found that maternal weight gain during pregnancy was independently associated with calcaneus QUS-SI in girls, and that grip strength was also significantly associated with calcaneus QUS-SI in both sexes. The present findings suggest that excessive restriction of maternal weight gain would have a negative effect on the calcaneus QUS-SI of girls, and that exercise and strength-building activities are likely to result in a higher calcaneus QUS-SI in both sexes of adolescents.

Association of Vegetable and Fruit Consumption with Urinary Oxidative Biomarkers in Teenaged Girls: A School-Based Pilot Study in Japan.

Hexanoyl-lysine (HEL), 8-hydroxy-2'deoxyguanosine (8-OHdG), and dityrosine (DT) have served as potential biomarkers for detecting oxidative modified lipids, DNA, and proteins in biological samples, respectively. Whether regular higher levels of consumption of vegetables/fruit (V/F) would decrease oxidative modification of these biomolecules in the body remain unelucidated. To examine the association of regular V/F consumption with the generation of these reactive oxygen species-induced biomarkers, this study evaluated V/F consumption in a school-based sample of teenaged girls (mean age 15.6 ± 1.7 years, n = 103), and quantified the formation of oxidative stress biomarkers in their urine. Only 19.4% and 23.3% of participants reported that they consumed the recommended daily amount of vegetables and fruits, respectively. Individuals who consumed lower levels of fruit (<100g/day) or vegetables (<250g/day) had significantly higher HEL excretion in their urine than those who consumed higher levels of fruit (≥100g/day) (p < 0.05) or vegetables (≥250g/day) (p = 0.057). The results of a multiple regression analysis showed that vegetable consumption was an important inhibiting factor of early lipid peroxidation measured as HEL in urine, independent of various confounders (ß = - 0.332, p < 0.05). The findings suggest that relatively higher consumption of vegetables would help in the prevention of early lipid peroxidation in adolescents.

Microwave Irradiation: Effects on the Change of Colour Characteristics and Main Phenolic Compounds of Cabernet Gernischt Dry Red Wine during Storage.

Wine colour is an essential organoleptic property considered by consumers. In this paper, the potential effects on colour characteristics and the content of main phenolic compounds in red wine under microwave irradiation were investigated during wine storage. The results showed that the changing trend of colour characteristics of microwave-treated and untreated wines was very similar. Moreover, total phenolic compounds, total monomeric anthocyanins, main anthocyanins, main flavonoids, and main phenolic acids (gallic acid; caffeic acid; syringic acid; (+)-catechin; Cy-3-glu; Mv-3-glu) also showed similar change trends during storage. In other words, microwave irradiation had a long-term effect on the colour properties and main phenolic compounds of red wine, changes that require long-time aging in traditional processing. In terms of the studied parameters, the changes in microwave-treated wine were faster than those in untreated wine. These results showed that microwave technology, as a promising artificial aging technology, could in a short time produce red wine of similar quality to traditional aging.

Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice.

Human acatalasemia may be a risk factor for the development of diabetes mellitus. However, the mechanism by which diabetes is induced is still poorly understood. The impact of catalase deficiency on the onset of diabetes has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of diabetogenic alloxan. The incidence of diabetes was higher in acatalasemic mice treated with a high dose (180 mg/kg body weight) of alloxan. A higher dose of alloxan accelerated severe atrophy of pancreatic islets and induced pancreatic beta cell apoptosis in acatalasemic mice in comparison to wild-type mice. Catalase activity remained low in the acatalasemic pancreas without the significant compensatory up-regulation of glutathione peroxidase or superoxide dismutase. Furthermore, daily intraperitoneal injection of angiotensin II type 1 (AT1) receptor antagonist telmisartan (0.1 mg/kg body weight) prevented the development of alloxan-induced hyperglycemia in acatalasemic mice. This study suggests that catalase plays a crucial role in the defense against oxidative-stress-mediated pancreatic beta cell death in an alloxan-induced diabetes mouse model. Treatment with telmisartan may prevent the onset of alloxan-induced diabetes even under acatalasemic conditions.

High serum arginase I levels in asthma: its correlation with high-sensitivity C-reactive protein.

BACKGROUND: Much attention has been directed to the induction of arginase I in the lung of asthmatic mice. However, there is no agreement on the changes of serum arginase activity in asthmatic patients among previous studies. OBJECTIVES: The aim of this study was to evaluate the clinical relevance of serum arginase I in asthmatic patients. METHODS: Serum arginase I was examined cross-sectionally in non-smoking asthmatic patients (n = 23) and healthy individuals (n = 30) using enzyme-linked immunosorbent assay (ELISA) and its correlations with several clinical parameters were investigated. RESULTS: Serum levels of arginase I were significantly increased in asthmatic patients (mean ± SD 67.4 ± 41.0 ng/mL) compared with healthy controls (27.2 ± 12.9 ng/mL). In healthy controls, a difference in arginase I levels was not observed between sex groups but was observed between age groups. In asthmatic patients, serum arginase I levels were not different between groups of age, sex, and inhalation steroid therapy but were different between groups of atopic status. Non-atopic asthmatic patients revealed significantly high serum arginase I levels compared with atopic asthmatic patients and healthy controls although no difference was observed between atopic asthmatic patients and healthy controls. Spearman's correlation analysis showed that serum arginase I level had a significant negative correlation with age and a positive correlation with red blood cell numbers in healthy controls, whereas in asthmatic patients, it had significant positive correlations with alanine aminotransferase (ALT), high-sensitivity C-reactive protein (hs-CRP) and a negative correlation with immunoglobulin-E (IgE). CONCLUSIONS: High serum arginase I levels in asthmatic patients may be associated with airway inflammation in non-atopic asthma.

The relationship between joint pain and climate conditions in Japan.

This study aimed to determine whether there was any association between the regional climate and the proportion of people with joint pain. Regional climate data between 1971 and 2000 were obtained from the Japan Meteorological Agency. The variables used in the cluster analysis included sunlight hours, amount of precipitation, number of days with precipitation, and temperature. The regional proportion of people with joint pain was obtained from the National Survey for Health in 2001. After performing a cluster analysis, one-way ANOVA and Welch's test were used to determine whether the climate characteristics of the clusters were significantly different. Within each cluster, stepwise multiple linear regression analyses were performed. We found that sunlight hours showed a direct, negative association with the proportion of people with joint pain (adjusted R2=0.532, p=0.016) in cluster 1, which was characterized as the region with the fewest total hours of sunlight, less precipitation, a modest number of rainy days, and low temperature. In the other clusters, the regional female population rate (cluster 2) and the senior population rate (cluster 3, 4) were the primary predictors. We concluded that the degree of exposure to sunlight may play a crucial role in prevention of joint pain. This finding should encourage people to set aside some time for staying outdoors in their daily lives.

Analysis of chemical compounds and toxicological evaluation of Forsythia suspensa leaves tea.

To determine the compositions of Forsythia suspensa leaves tea (FSLT) and its safety, the chemical compounds were analysed with some methods, and the toxicity was evaluated in Kunming mice and Wistar rats. The results showed that FSLT contained rich flavonoid, lignans, triperpene acids, amino acids, and mineral elements. In the acute toxicity study, none of the mice died, and no obvious poisoning symptoms were observed after 14 days in mice at the dose of 15 mg/g·body weight (bw) FSLT; in the sub-chronic toxicity, no abnormal or dead rat was found at the dose of 1, 3, and 10 mg/g·bw during 90 days feeding administration; there was no significant difference in bw and food consumption; no significant differences were found in each hematology and serum biochemistry parameter and organ/body weight ratio comparing with the control experimental group. The results revealed that the FSLT has low or no toxicity via oral administration. Therefore, FSLT is very suitable and safe to be used as a new resource food.

Direct inhibition of arginase attenuated airway allergic reactions and inflammation in a Dermatophagoides farinae-induced NC/Nga mouse model.

The expression of arginase I has been a focus of research into the pathogenesis of experimental asthma, because arginase deprives nitric oxide synthase (NOS) of arginine and therefore participates in the attenuation of bronchodilators such as nitric oxide (NO). The present study used an intranasal mite-induced NC/Nga mouse model of asthma to investigate the contribution of arginase to the asthma pathogenesis, using an arginase inhibitor, N(omega)-hydroxy-nor-l-arginine (nor-NOHA). The treatment with nor-NOHA inhibited the increase in airway hyperresponsiveness (AHR) and the number of eosinophils in bronchoalveolar lavage fluid. NOx levels in the lung were elevated despite suppressed NOS2 mRNA expression. Accompanied by the attenuated activity of arginase, the expression of arginase I at both the mRNA and protein level was downregulated. The levels of mRNA for T helper 2 cytokines such as IL-4, IL-5, and IL-13, and for chemotactants such as eotaxin-1 and eotaxin-2, were reduced. Moreover, the accumulation of inflammatory cells and the ratio of goblet cells in the bronchiole were decreased. The study concluded that the depletion of NO caused by arginase contributes to AHR and inflammation, and direct administration of an arginase inhibitor to the airway may be beneficial and could be of use in treating asthma due to its anti-inflammatory and airway-relaxing effects, although it is not clear whether the anti-inflammatory effect is direct or indirect.

The role of catalase in pulmonary fibrosis.

BACKGROUND: Catalase is preferentially expressed in bronchiolar and alveolar epithelial cells, and acts as an endogenous antioxidant enzyme in normal lungs. We thus postulated epithelial damage would be associated with a functional deficiency of catalase during the development of lung fibrosis. METHODS: The present study evaluates the expression of catalase mRNA and protein in human interstitial pneumonias and in mouse bleomycin-induced lung injury. We examined the degree of bleomycin-induced inflammation and fibrosis in the mice with lowered catalase activity. RESULTS: In humans, catalase was decreased at the levels of activity, protein content and mRNA expression in fibrotic lungs (n = 12) compared to control lungs (n = 10). Immunohistochemistry revealed a decrease in catalase in bronchiolar epithelium and abnormal re-epithelialization in fibrotic areas. In C57BL/6J mice, catalase activity was suppressed along with downregulation of catalase mRNA in whole lung homogenates after bleomycin administration. In acatalasemic mice, neutrophilic inflammation was prolonged until 14 days, and there was a higher degree of lung fibrosis in association with a higher level of transforming growth factor-ß expression and total collagen content following bleomycin treatment compared to wild-type mice. CONCLUSIONS: Taken together, these findings demonstrate diminished catalase expression and activity in human pulmonary fibrosis and suggest the protective role of catalase against bleomycin-induced inflammation and subsequent fibrosis.

Evaluation of pyrogallol-induced cytotoxicity in catalase-mutant escherichia coli and mutagenicity in Salmonella typhimurium.

We evaluated pyrogallol cytotoxicity using Escherichia coli strains that express mammalian catalase gene derived from catalase mutant mice (Cs(b)) and wild-type (Cs(a)), and pyrogallol mutagenicity by Ames test. Pyrogallol was more toxic to Cs(b) rather than to Cs(a) (p < 0.05), while catalase, superoxide dismutase and ascorbic acid decrease the toxic effect. Pyrogallol also showed mutagenic effect (mutagenic index = 3.8 for 10 micromol pyrogallol/plate) while ascorbic acid (19.4% reduction, p < 0.001) and naringin (35.1% reduction, p < 0.001) played a protective role against it. Pyrogallol cytotoxicity and mutagenicity seem to be attributable, at least in part, to reactive oxygen species formation. This study also suggests that newly established catalase mutant E. coli is probably useful in hazard identification of oxidative chemicals.

Psychosocial Determinants of Fruit and Vegetable Intake in Japanese Adolescents: A School-Based Study in Japan.

A few studies in Japan have demonstrated positive attitudes, self-efficacy, social support, and perceived barrier were associated with fruit and vegetable (F&V) intake in adults; however, limited evidence addresses the association of psychosocial factors with F&V intake in adolescents. A cross-sectional study through a questionnaire survey was conducted at junior and senior high schools, and 933 students completed the questionnaire. Data were analyzed by X2 test and Student t-test. The findings demonstrated 2.7% of participants were aware of the current recommendations for vegetable and 2.0% for fruit. Only 4% and 8.1% of participants reported they consumed recommended amount of vegetables and fruits. In comparison with males, females showed higher scores of attitude (p < 0.01), responsibility (p < 0.01), and social support (p < 0.01). The barriers to vegetable intake were "I'm eating enough now", "not always available when eating away from home"; the barriers to fruit intake were "don't have a habit of having 100% juice or fruit in the morning", and "cost too much". The findings suggest the change of adolescents' knowledge about what they should eat is needed in boosting F&V consumption. The development of an intervention program for adolescents needs to target socio-environmental factors such as family support, and nutritional education for early healthy habit formation.

Effects of a Forest Walk on Urinary Dityrosine and Hexanoyl-Lysine in Young People: A Pilot Study.

A few studies indicate exposure to forests may alleviate oxidative stress in the body. However, more evidence is needed to support this potentiality. The purpose of the current study aimed at examining whether there is any difference in urinary levels of oxidatively modified proteins or lipids-dityrosine (DT) and hexanoyl-lysine (HEL), respectively, after a forest or urban walk. The study was performed on 29 university students who took part in forest walks (Shinjo Village) in Okayama Prefecture of Japan and on 42 university students who took part in urban walks in the downtown area of Okayama City. Urine samples before and after the walks were analyzed for DT and HEL excretion. Air phytoncides during the walks were also measured. We found a decreased tendency in urinary DT and HEL (p < 0.05) in most participants after the forest walks, but not after the urban walks. We further found the total levels of air phytoncides in the forest field were 1.50 times higher compared with those in the urban field. This study suggests the possibility that regular immersion in a forest environment might contribute toward weakening of the oxidative modifications of proteins or lipids in the body.

Effect of hydrogen peroxide on normal and acatalasemic mouse erythrocytes.

OBJECTIVES: Normal and acatalasemic mouse erythrocytes were used to clarify the relationship between oxidative damage in H2O2-treated erythrocytes and catalase activity. DESIGN & METHODS: Generation of hydrolysis-resistant erythrocytes and hemolysis were examined. The osmotic fragility test, the negative charges and the number of membrane-flickering erythrocytes among the H2O2-treated erythrocytes were investigated. RESULTS: Small amounts of hydrolysis-resistant mouse erythrocytes were generated by treatment with 0.1 mM H2O2, and the amount of acatalasemic erythrocytes was larger than untreated controls. Hemolysis in the acatalasemic erythrocytes was observed 30 min after the addition of the H2O2. A drastic increase in hydrolysis-resistant erythrocytes and a loss of membrane proteins in the acatalasemic erythrocytes were found as a result of the addition of 1 mM H2O2. Hemolysis in normal erythrocytes was observed at 3 mM H2O2. CONCLUSIONS: Catalase is a potent H2O2-scavenger even in acatalasemic mouse erythrocytes. It is concluded that the drastic increase of hydrolysis-resistant erythrocytes is induced by a loss of membrane function and is associated with the low catalase activity in these cells.

Relationship of psychological factors with physical activity stage of change in prime-and middle-aged Japanese.

The present study aimed to investigate the status of physical activity and the differences in psychological factors associated with physical activity from the perspective of transtheoretical model stages between prime- and middle-aged Japanese. The study involved 375 prime-aged volunteers (175 men, 200 women) and 557 middle-aged volunteers (247 men, 310 women) living in Kuse, a town in Okayama Prefecture, Japan. We found that the prime-aged men at the preparation stage had significantly higher self-efficacy scores than at the contemplation stage (p<0.01). Middle-aged men had significantly higher self-efficacy scores at the contemplation stage than at the precontemplation stage (p<0.001). Middle-aged women, meanwhile, had significantly higher self-efficacy scores at the maintenance stage than at the action stage (p<0.01), and at the contemplation stage than at the precontemplation stage (p<0.001). The present findings provide valuable information about the differences in psychological factors affecting physical activity between prime-aged and middle-aged community-dwelling Japanese. This information may be useful to health professionals as they develop effective community-based intervention programs for target populations.

Oxidative stress biomarkers and lifestyles in Japanese healthy people.

The urinary concentrations of 8-isoprostane and 8-hydroxy-2'-deoxyguanosine (8-OHdG), which are biomarkers of oxidative stress, were measured in 677 Japanese people without any diseases, and their correlations with lifestyle facotrs, lifestyle-related blood biochemical parameters, and dietary intake of antioxidative vitamins were investigated. The mean urinary concentration of 8-isoprostane and 8-OHdG was 0.58 ng/mg creatinine and 8.43 ng/mg creatinine, respectively. Mean urinary 8-isoprostane was significantly different in terms of age, gender, smoking and alcohol consumption but not different in terms of body mass index (BMI) and exercise. By multiple regression analysis, urinary 8-isoprostane was significantly influenced by smoking and age. On the other hand, mean urinary 8-OHdG showed differences only by age group. Multiple regression analysis revealed that urinary 8-OHdG was significantly influenced by age, smoking, body weight, levels of high-sensitivity C-reactive protein (Hs-CRP) and low density lipoprotein-cholesterol in females, although it was significantly influenced by body weight in males. The present study shows that urinary 8-isoprostane is associated with lipid peroxidation related-lifestyles such as smoking, and urinary 8-OHdG is associated with arteriosclerosis related-factors such as Hs-CRP. Our findings suggest that 8-isoprostane and 8-OHdG appear to be prospective biomarkers for early prediction of lifestyle related-disease risk at the population level.

Increased susceptibility to oxidant-mediated tissue injury and peritoneal fibrosis in acatalasemic mice.

BACKGROUND: Peritoneal fibrosis is a major complication leading to the loss of peritoneal function in patients undergoing peritoneal dialysis. However, the effect of catalase depletion on peritoneal fibrosis has not yet been investigated. METHODS: The impact of catalase deficiency on progressive peritoneal fibrosis has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 14 days. RESULTS: The CG injections resulted in a thicker peritoneal membrane, reflecting peritoneal fibrosis with accumulation of interstitial type I collagen, peritoneal deposition of lipid peroxidation products (4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal), and an elevated level of 8-hydroxy-2'-deoxyguanosine in peritoneal fluid in both mouse groups on day 14. The extent of these changes, however, was significantly higher in acatalasemic mice than in wild-type mice. The level of catalase activity remained low in the acatalasemic peritoneum without the compensatory upregulation of glutathione peroxidase, but with an insufficient upregulation of superoxide dismutase activity in CG-injected mice. CONCLUSIONS: Acatalasemia, therefore, exacerbates oxidant tissue injury and induces the peritoneum to develop irreversible fibrosis which is the most important complication of peritoneal dialysis. This study suggests that catalase plays a crucial role in the defense against oxidant-mediated peritoneal injury in a mouse peritoneal fibrosis model.