Determining the Safety and Influence of Various Immunosuppressant Regimens in a Streptozotocin Induced Diabetic Rat Model

This poster was presented at the SOT ToxExpo March 2017 in Baltimore, MD.  Presenting Author: Rohit Rajoria, Ph.D.

Basic maintenance immunosuppression in preventing autoimmune disease and organ-transplant rejection typically includes the following drugs: a purine antagonist (mycophenolate), a glucocorticoid (prednisone), and/or calcineurin inhibitor (cyclosporine).  For patients that develop diabetic sequela requiring organ transplants, considerations should be factored due to the growing concern for chronic immunosuppression treatment and its influence on diabetes mellitus (DM).   As recipients of organ transplants survive longer, these complications of DM provide the impetus for the development of an in-vivo model in determining the safety and efficacy of chronic immunosuppressant dose regimens without exacerbating the pre-existing diabetic condition. In this study, a model of diabetes mellitus (DM) was achieved in Sprague Dawley rats by an intraperitoneal injection of streptozotocin (STZ).  All DM rats achieved a hyperglycemic state (> 450 mg/dL) four weeks before dosing, and were provided insulin (Humalog®) daily.  Upon confirmation of chronic DM, immunosuppressant dose regimens were orally administered daily (BID) based on testing groups: (1) mycophenolate sodium [MS]; (2) MS with cyclosporine; (3) MS with prednisone; (4) Vehicle only; (5) Non-DM  vehicle.  Clinical pathology, gross necropsy, and histopathology of vital organs was performed to assess safety of the aforementioned immunosuppressant regimens in this model.
The objective of this poster is to evaluate the impact and safety of various immunosuppressant regimens used in clinical management of patients with diabetic sequela, autoimmune disease, and/or  recipients of  organ transplantation using an in vivo rodent model of diabetes mellitus (DM).

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