Reduction of diabetes-induced renal oxidative stress by a cantaloupe melon extract/gliadin biopolymers, oxykine, in mice

【目的】糖尿病性腎症の発症・進展に酸化ストレスの関与が示されている.本研究では2型糖尿病モデルマウスC57BL/KsJ db/dbマウスを用いて,オキシカイン(Superoxide dismutase高含有南フランス産特別種メロン抽出物と小麦グリアジンの複合体)投与による糖尿病性腎症の進展抑制効果について評価した.【方法】6週齢雄C57BL/KsJ-db/dbマウスを対照食とオキシカイン混餌食で飼育し,18週齢まで経時的に体重,随時血糖,尿中アルブミン排泄量,尿中8-hydroxydeoxyguanosine(8-OHdG)の測定を行った.また,腎臓組織を用い8-OHdGの免疫組織化学により酸化ストレスを組織学的に評価した.【結果】両群において,随時血糖,体重増加量に有意な差は見られなかった.対照群では尿中アルブミンの増加とともに尿中8-OHdGの有意な増加を認め,免疫組織学的にも腎組織中8-OHdG陽性細胞数は有意に高値であった.【結論】糖尿病性腎症の発症進展抑制に,オキシカインが有用である可能性が示唆された.Oxidative stress is implicated as an important mechanism by which diabetes causes nephropathy. Oxykine is the cantaloupe melon extract rich in vegetal superoxide dismutase covered by polymeric films of wheat matrix gliadin. In this study, we examined whether chronic oral administration of oxykine could prevent the progression of diabetic nephropathy induced by oxidative stress using preclinical rodent model of type 2 diabetes. We used female db/db mice and their nondiabetic db/m littermates. The mice were divided into the following three groups: non-diabetic db/m; diabetic db/db, and diabetic db/db treated with oxykine. Blood glucose level, body weight, urinary albumin, and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured during the experiments. Histological and 8-OHdG immunohistochemical studies were preformed on 12 weeks from the beginning of treatment. After 12 weeks of treatment, the levels of blood glucose and the body weight were not significantly different between the oxykine-treated group and the non-treated db/db group, however both groups kept significantly high levels rather than db/m mice. The relative mesangial area calculated by mesangial area/total glomerular area ratio was significantly ameliorated in the oxykine treated group compared with non-treated db/db group. The increases in urinary albumin and 8-OHdG at 12 weeks of treatment were significantly inhibited by chronic treatment with oxykine. The 8-OHdG immunoreactive cells in the glomeruli of non-treated db/db mice were more numerous than that of oxykine-treated db /db mice. In this study, treatment of oxykine ameliorated the progression and acceleration of diabetic nephropathy for rodent model of type 2 diabetes. These results indicated that the oxykine reduced the diabetes-induced oxidative stress and renal mesangial cell injury. In conclusion, oxykine might be a novel approach for the prevention of diabetes nephropathy