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Int J Mol Med. 2003 Dec;12(6):949-54.

Alteration in serum and bone component findings induced in streptozotocin-diabetic rats is restored by zinc acexamate.

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Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.


The effect of zinc acexamate in streptozotocin (STZ)-induced diabetic rats was investigated. Rats received a single subcutaneous administration of STZ (6.0 mg/100 g body weight), and the animals were orally administered once daily for 14 days with zinc acexamate (2.5, 5 or 10 mg/100 g body weight). The administration of STZ caused a significant increase in serum glucose, triglyceride and calcium levels and a significant decrease in body weight, serum zinc and inorganic phosphorus levels, indicating diabetic condition. Moreover, calcium content, alkaline phosphatase activity and deoxyribonucleic acid (DNA) content in the femoral-diaphyseal and -metaphyseal tissues were significantly reduced in STZ-diabetic rats. The change in these serum and bone components of STZ-diabetic rats was significantly restored by the oral administration of zinc acexamate (2.5, 5 or 10 mg Zn/100 g body weight). The restoration of bone components was not seen by the oral administration of zinc sulfate (2.5 mg Zn/100 g) for 14 days. Moreover, when the femoral-diaphyseal and -metaphyseal tissues obtained at 14 days after STZ administration were cultured for 48 h in a medium containing either vehicle or zinc acexamate (10(-5) M), the femoral calcium content and alkaline phosphatase activity were significantly increased in vitro. The effect of zinc acexamate was completely abolished in the presence of cycloheximide (10(-6) M), an inhibitor of protein synthesis. The present study demonstrates that the oral administration of zinc acexamate has a preventive effect on STZ-induced diabetic condition in rats, and that it can restorate bone loss of STZ-induced diabetes in vivo.

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