Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 8 No. 4 August 02, 2021 p.97-101
Antidiabetic agent did not impair spermatogenesis in spontaneously hyperglycemic and diabetic rats
  • Taiki Kobayashi (Graduate School of Veterinary Science, Azabu University / TEIJIN PHARMA LIMITED /
Taiki Kobayashi 1) 2) , Takasumi Shimomoto 2) , Junichi Namekawa 2) , Masanobu Kanou 3) , Hirotsugu Kato 2) , Seishiro Sakamoto 2) , Takeshi Iijima 2) , Hideharu Ochiai 1)
1) Graduate School of Veterinary Science, Azabu University , 2) TEIJIN PHARMA LIMITED , 3) TEIJIN LIMITED
Keywords: Hypoglycemia, Testicular toxicity, Testis, Sperm, Germ cell, Reproductive organs

In previous studies, we suggested that hypoglycemia induced by antidiabetic drugs causes testicular toxicity. In this study, we evaluated whether spontaneously hyperglycemic and diabetic rats (Goto-Kakizaki rats) treated with an antidiabetic drug showed testicular histopathological changes. TMG-123, a glucokinase activator, was given to the rats for 4 weeks at 12.5, 25 and 50 mg/kg. The exposures of TMG-123 at 50 mg/kg were similar to those that caused hypoglycemia and testicular toxicity in SD rats, and the decrease in blood glucose levels on day 28 of dosing was similar to that in SD rats, which showed that the pharmacological action of TMG-123 was similar in both SD and Goto-Kakizaki rats. However, blood glucose levels in Goto-Kakizaki rats were originally much higher than those in SD rats, and hypoglycemia was not induced in the Goto-Kakizaki rats. The histopathological evaluation showed no testicular changes. These results corroborate our hypothesis.