Kitaro Oka

Protective effect of caffeine on streptozotocin‐induced beta‐cell damage in rats

Many epidemiological studies have shown that coffee consumption reduces the risk of type 2 diabetes mellitus (T2D), although the reasons as to why remain unclear. In this study we investigated the effect of caffeine on pancreatic beta‐cell damage in rats using the diabetogenic agent, streptozotocin (STZ). Wistar rats were given intraperitoneal injections of saline or caffeine (10, 50 or 100 mgkg−1). After 15 min, the rats were injected with a citrate buffer or 65 mgkg−1 STZ. Three days after injection, an oral glucose tolerance test (OGTT) was performed on the rats. Furthermore, three days after the OGTT, the pancreas was isolated and homogenized, followed by determination of insulin content. STZ treatment significantly increased the plasma glucose level compared with the control at all times during the OGTT, which was significantly diminished by caffeine pretreatment at all doses. STZ treatment significantly decreased the plasma insulin level, however, which was not recovered by caffeine pretreatment. Pancreatic insulin content was significantly reduced by STZ treatment compared with the control, which was significantly recovered by caffeine pretreatment at a dose of 100 mgkg−1 (P < 0.01). We showed that caffeine protects pancreatic beta‐cells against STZ toxicity. Further investigation will be required to understand the protective effect of caffeine against beta‐cell destruction in T2D.

Protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine induced acute liver injury in rats.

Objectives The protective effects of coffee‐derived compounds on lipopolysaccharide/d‐galactosamine (LPS/d‐GalN) induced acute liver injury in rats were investigated.

Suppression of blood lipid concentrations by volatile Maillard reaction products

OBJECTIVE Although the chemistry of Maillard reaction products (MRPs) in foods has been well studied, few reports on the nutritional characteristics of MRPs in experimental animals and humans have been found. In this study, our interest was focused on the volatile MRPs (vMRPs) found in heated foods. METHODS To confirm the metabolic oxidations of six methylpyrazines and pyrrole-2-carboxaldehyde to carboxylic acid derivatives in vivo, we administrated these compounds orally to Wistar rats with a single dose of 50 mg/kg. Urine samples were collected over 24 h, followed by determination using high-performance liquid chromatographic procedures. Eight pyrazinoic acids, 2-furoic acid, and 5-hydroxymethyl-2-furoic acid were administered orally to rats with a single dose of 100 or 300 mg/kg, and blood non-esterified fatty acid and triacylglycerol concentrations were analyzed. RESULTS Monomethylpyrazine, 2,3-, 2,5-, and 2,6-dimethylpyrazine, trimethylpyrazine, and tetramethylpyrazine were metabolized to a corresponding pyrazinoic acid such as non-substituted pyrazinioic acid, 3-, 5-, or 6-methylpyrazinoic acid, 3,5-, 3,6-, and 5,6-dimethylpyrazinoic acid, and trimethylpyrazinoic acid, in appropriate yields, respectively. Further, pyrrole-2-carboxaldehyde was metabolized to pyrrole-2-carboxylic acid. Non-substituted and 5-methylpyrazinoic acid and 2-furoic and 5-hydroxymethyl-2-furoic acid showed significant non-esterified fatty acid-lowering effects. 5-Methyl and 6-methylpyrazinoic acid and 2-furoic acid showed significant triacylglycerol-lowering effects. Pyrazinoic acids with methyl substitution at position 3 showed no lipid-lowering effect. CONCLUSION These results suggest that the vMRPs such as methylpyrazines are metabolized to their corresponding pyrazinoic acids. These vMRPs and their metabolites exhibit blood lipid-lowering effects in rats.

Suppressive potencies of calcineurin inhibitors against the mitogen-induced blastogenesis of peripheral-blood mononuclear cells of myasthenia gravis patients

The calcineurin inhibitors, tacrolimus and ciclosporin, are two useful immunosuppressive drugs for the treatment of myasthenia gravis (MG), for patients who have low responses to glucocorticoids. We have studied the suppressive potencies of tacrolimus and ciclosporin on concanavalin A‐induced blastogenesis of peripheral‐blood mononuclear cells (PBMCs) obtained from 38 MG patients and 26 healthy volunteers. Differences in the IC50 values of the two calcineurin inhibitors between the patients and the healthy subjects were evaluated. The median (range) IC50 values for tacrolimus and ciclosporin on the blastogenesis of PBMCs of MG patients were 0.06 (0.001–100) and 0.41 (0.09–83.0) ng mL−1, respectively. In contrast, the median (range) IC50 values of tacrolimus and ciclosporin on healthy PBMCs were 0.16 (0.001–0.33) and 5.59 (1.4–31.3), respectively, and thus ciclosporin potencies against PBMCs of MG patients were significantly higher than those against PBMCs of healthy subjects (P < 0.0001). The differences in tacrolimus IC50 values between the patients and healthy subjects were not significant. There was a correlation between ciclosporin IC50 values against the blastogenesis of PBMCs of MG patients and the duration of the disease (r = 0.35, P = 0.049). A significant correlation between the IC50 values of ciclosporin and those of prednisolone against the blastogenesis of PBMCs of MG patients was also observed (r = 0.56, P = 0.003). Furthermore, the ciclosporin IC50 values significantly correlated with the periods of glucocorticoid administration for MG treatment (r = 0.42, P = 0.038). Such correlations were not observed with the tacrolimus IC50 values. These results suggested that glucocorticoid administration had an influence on PBMC response to the suppressive efficacy of ciclosporin in MG.