| Potential for Antioxidant Therapy for Diabetes and Diabetic Complications Yoshiaki Harakawa1; Fuhua Yang1; Toshikazu Yoshikawa2; Haruhiko Inufusa3; 1DIVISION OF ANTI-OXIDANT RESEARCH, GIFU UNIVERSITY, Gifu, Japan; 2LOUIS PASTEUR CENTER, Kyoto, Japan; 3TIMA, Gifu, Japan; PAPER: 426/Oxidative/Regular (Oral) SCHEDULED: 14:50/Tue. 29 Nov. 2022/Ballroom B ABSTRACT: Diabetes is known to be a disease caused by oxidative stress, and also known to generates its own oxidative stress, resulting in numerous complications. Twendee X (TwX) is an antioxidant combination supplement with international and Japanese patents, and has been certified as effective in preventing dementia from a randomized, double-blind clinical trial led by the Japan Society for Dementia Prevention in 2019. In recent years, we have also successfully developed Twendee Mtcontrol (TwM), an antioxidant with seven more ingredients added to TwX to increase its antioxidant effect. The antioxidants TwX and TwM were tested in animal models to see if they can treat diabetes and diabetic complications. To examine the effect of antioxidants on diabetes, a diabetic disease model was developed. TwX or TwM was orally administered daily for 2 months. Afterwards, a glucose tolerance test was performed, and blood glucose levels were measured over time. In addition, insulin levels were measured under the same conditions. The results showed that the peak blood glucose level was significantly improved in the TwX group, and the peak level was also improved in the TwM group compared to the control group. Insulin levels also tended to be lower than controls in both groups. In addition, to verify the effectiveness of the supplements in preventing actual diabetic complications, we tested it on SDT fatty rats, which develop diabetic complications early in the course of the disease. These rats develop elevated blood pressure and cataracts at a much earlier stage due to the progression of diabetes mellitus. SDT fatty rats (5-week-old males) were divided into three groups (n=8): control (non-treated), TwX 40 mg/kg/Day, and TwM 40 mg/kg/Day. At 17 weeks of age, most rats in the non-treated group showed severe cataracts, whereas those in the TwM-treated group had relatively mild cataracts. Systolic blood pressure also tended to increase with age in the non-treated group, but the TwX and TwM groups significantly suppressed the age-related increase in blood pressure. These results suggest that TwX and TwM reduced blood glucose levels in an insulin-independent manner, thereby reducing diabetic complications such as hypertension and cataracts. TwX reduced blood glucose levels more, and TwM had a pronounced cataract-preventive effect. TwM may have a broader range of disease-preventive effects. however, further studies are required for the detailed mechanism of action. These results suggest the possibility of antioxidant therapy for diabetes mellitus and its complications. References: [1] Yamagishi S. [Diabetes and Oxidative Stress] Tounyoubyou to Sanka Sutoresu (in Japanese), Medical Review Co., Ltd., 2011, 3.<br />[2] Masuyama T, Katsuda Y, and Shinohara M. A novel model of obesity-related diabetes: introgression of the Lepr<sup>fa</sup> allele of the Zucker fatty rat into nonobese Spontaneously Diabetic Torii (SDT) rats. Exp. Anim. 54(1): 13-20, 2005.<br />[3] Matsui K, Ota T, Matsushita M, et al. Diabetes-associated complications in Spontaneously Diabetic Torii Fatty Rats. Exp. Anim. 57(2): 111-121, 2008. |
