A phenomenon of hypersensitivity to the diabetogenic effect of total RNA in rats that had alloxan diabetes

Abstract

Introduction. As we have shown earlier, preparations of allogenic total RNA from lymphoid and stem cells contribute to normalization of blood glucose levels in white outbred rats with persistent alloxan-induced diabetes. The aim of this study was to evaluate the effect of total RNA from the spleen of rats with alloxan diabetes on blood glucose of intact and post-alloxan diabetic animals. Method. Experiments were performed on 34 white outbred female rats weighing 250-280 g. Rats were divided into intact animals (n=12) and rats with experimental alloxan diabetes mellitus (n=22). Diabetes mellitus was modeled by a single subcutaneous (s.c.) injection of complete Freund’s adjuvant (0.5 ml) followed by a s.c. injection of alloxan trihydrate (200 mg/kg). Spleens from 10 rats with alloxan diabetes were used for obtaining total RNA. In the remaining 12 rats with alloxan diabetes, the level of blood glucose was completely normalized by administration of total RNA from the bone marrow, spleen, and pancreas (post-diabetes group). On day 45 of this experiment, 12 intact rats and 12 post-diabetes rats were used for a new experiment (second stage protocol). Alloxan diabetes was induced in 6 intact rats (for the first time) and 6 post-diabetes rats (for the second time) by a s.c injection of alloxan 100 mg/kg. The remaining 6 rats of the intact control group and 6 rats of the post-diabetes group received an injection of total RNA (15 μg/100 g body weight, i.p.). Results. Administration of total RNA (15 μg/100 g body weight) induced hyperglycemia in all experimental animals, which was comparable with the effect of a 600-700-fold dose of alloxan. Rats that had previously had diabetes responded to the total RNA significantly stronger. Likewise, a repeated exposure to alloxan of post-diabetes rats induced significantly more pronounced hyperglycemia than the response to alloxan of intact rats. Conclusions. This study discovered a phenomenon of hypersensitivity to repeated exposure to alloxan and to the diabetogenic effect of total RNA in animals that had previously had alloxan diabetes. This effect suggests a possibility of using the total RNA of lymphoid cells to create animal models of human diseases and to develop new approaches in personalized medicine.