Razi Journal of Medical Sciences

Background: All-trans retinoic acid (ATRA) has a variety of biological activities, including immunomodulatory action in a number of inflammatory and autoimmune diseases. The purpose of this study was to investigate the effects of all-trans retinoic acid on the treatment of autoimmune diabetes in mice and its effects on expressions of Peroxisome Proliferator-Activated Receptor gamma (PPARγ) gene.

Methods: Diabetes was induced by multiple low-dose of streptozotocin (MLDS) injection (40mg/kg/day for 5 consecutive days) in male C57BL/6 mice. After induction of diabetes, mice were treated with ATRA (20mg/kg/day i.p.) for 21 days. Blood glucose level was measured in 0, 7, 14 and 21 days after Streptozotocin induction induced diabetes. Splenocytes were tested for cytokines production by ELISA and Immune changes in spleens were tested by semi-quantitative RT-PCR. One-way analysis of variance (ANOVA) followed by Tukey’s test were used for comparisons between groups. P<0.05 was considered significant.

Results: ATRA treatment prevented hyperglycemia in the diabetic mice. ATRA treatment also significantly inhibited the production of proinflammatory cytokines interleukin 17 (IL-7) as well as interferon gamma (IFN-γ) while increased the level of anti-inflammatory cytokine IL-10 and upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) gene expression in spleens as compared with those in diabetic control group.

Conclusion: In conclusion, these findings indicate that ATRA may have a therapeutic effect against the autoimmune destruction of the pancreatic beta-cells during the development of MLDS-induced type 1 diabetes in mice.