Da Hong Wang

Enhanced liver injury in acatalasemic mice following exposure to carbon tetrachloride

The hypothtical involvement of hydrogen peroxide (H2O2) in carbon tetrachloride (CCl4)-induced acute liver injury and the potential preventive effect of catalase on hepatotoxicity have been studied in acatalasemic (C3H/AnLCsbC2b) mice and compared with normal (C3H/AnLCsaCsa) mice. A single intraperitoneal injection of CCl4 (20% in olive oil/g body weight) caused increases in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in both mouse groups, but the extents of increases did not show significant differences between the two mouse groups until 12 h. The variation in increases of serum AST and ALT levels in acatalasemic and normal mice turned to be distinctly different from 12 h. At 18 h (peak point for ALT) and 24 h (peak point for AST), the serum enzyme levels in acatalasemic mice were nearly two-fold higher than those in normal ones, the difference being statistically significant (p <0.01). The liver malondialdehyde (MDA) level in acatalasemic mice was also higher than that in normals at 18 h (p <0.05). The extent of the centrilobular necrosis was histologically more severe in acatalasemic mice. The catalase activity in livers of acatalasemic mice was one-third to one-fifth those of normal mice (p <0.05) before and after treatment. The decreased catalase activity in acatalasemic mice might increase tissue or cellular levels of H2O2 during the later phase of the acute liver injury. From these findings, we conclude that H2O2 breakdown in liver would account for the difference in the later stages of the acute liver damage between the two groups of mice, and catalase is important in inhibiting hepatotoxicity of CCl4 in the later stage.

Comparison of serum ferritin and oxidative stress biomarkers between Japanese workers with and without metabolic syndrome

OBJECTIVEnMetabolic syndrome (MS) is closely associated to life-style and is characterized by central obesity causing severe diseases such as diabetes mellitus (DM) or atherosclerosis. This study investigates the role of oxidative stress and inflammation in MS.nnnSUBJECTSnTotal of 685 workers stratified by gender (293 men and 392 women) with a mean age of 41.2 ± 10.4 in different offices in a city in Japan.nnnMETHODSnFasting blood and urine tests for MS, oxidative and/or inflammatory biomarker analysis and blood pressure (BP) measurement were performed. MS was defined on the basis of the Japanese criterion.nnnRESULTSnSerum ferritin and urinary hydrogen peroxide (H2O2) levels were significantly higher in subjects with MS than those without. Ferritin was positively correlated with 8-hydroxy-2-deoxyguanosine (8-OHdG) in all subjects and it was negatively correlated with 8-isoprostane and H2O2 in men. In addition, there was a significant positive correlation between ferritin and homeostasis model assessment (HOMA-R) in men. By using multiple regression analysis, ferritin was closely correlated with HOMA-R, γ-GT, 8-OHdG, smoking value and amount of alcohol ingestion in men, and it was correlated with 8-OHdG, γ-GT, HOMA-R in women under 50 years old.nnnCONCLUSIONSnFerritin is a useful marker of MS including insulin resistance, reflecting the importance of oxidative stress as a cause of MS, especially in men.

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.

No Different Sensitivity in Terms of Whole-Body Irradiation between Normal and Acatalasemic Mice

To elucidate the radiosensitivity of an acatalasemic mouse, we examined the time and dose-dependency in the survival rates, the lymphocytes and the intestinal epithelial cells, and the antioxidant function after 3.0 to 12.0 Gy whole body irradiation. Results showed that no significant differences between acatalasemic mice and normal mice were observed in the survival rates and the histological changes in spleens and small intestine after each irradiation. The catalase activities in livers and spleens of acatalasemic mice were significantly lower than those of normal mice and the glutathione peroxidase activity in livers of acatalasemic mice was significantly higher than that of normal mice. At 10 days after 6.0 Gy irradiation, the catalase activities in livers of acatalasemic and normal mice and that in spleens of normal mice significantly decreased compared with no-irradiation control, and there were no differences between those catalase activities. The total glutathione content in acatalasemic mice was significantly higher than that in normal mice at 10 days after 6.0 Gy irradiation. These findings suggested that the radiosensitivity of acatalasemic mice in terms of whole body irradiation doesn’t significantly differ from that of normal mice, probably due to compensated sufficient contents of glutathione peroxidase and total glutathione in acatalasemic mice.