Blood glucose lowering and toxicological effects of zinc (II) complexes with maltol, threonine, and picolinic acid.
The blood glucose lowering effects in KK-Ay mice with type 2 diabetes mellitus (DM) receiving daily an intraperitoneal (i.p.) administration of Zn(II) complexes with maltol, L-threonine, and picolinic acid for 14 days were estimated under the same conditions, and dose-dependent blood glucose lowering effects in the dose range of 0.2-3.0 mg Zn/kg body weight were found. Among them, the bis(maltolato)Zn(II) complex exhibited the highest blood sugar lowering effect at the dose of 3.0 mg Zn/kg. The improvement of DM was confirmed with oral glucose tolerance tests as well as blood HbA1c levels after the administration of the three Zn(II) complexes at the dose of 3.0 mg Zn/kg. For the purpose of the clinical trial of the complexes in the future, we examined the toxic effects of these three Zn(II) complexes in regard of the LD50 values and hepatic cytochrome P450 levels. The LD50 values of the three Zn(II) complexes exhibited high values compared with that of ZnCl2. No changes of both CYP1A1 and CYP2E1 levels in the liver of KK-Ay mice treated with the three Zn(II) complexes were observed. The obtained results will be important when the complexes are tried for clinical use.
Kojima
Yoshitane
Y
Department of Chemistry, Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
Yoshikawa
Yutaka
Y
Ueda
Eriko
E
Kondo
Mayuko
M
Takahashi
Saeko
S
Matsukura
Takefumi
T
Sakurai
Hiromu
H
Hiroi
Toyoko
T
Imaoka
Susumu
S
Funae
Yoshihiko
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010848:Picolinic Acids / Q000494:pharmacology* / Q000633:toxicity; D011753:Pyrones / Q000494:pharmacology* / Q000633:toxicity; D013912:Threonine / Q000494:pharmacology* / Q000633:toxicity; D017967:Zinc Compounds / Q000494:pharmacology* / Q000633:toxicity
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010848:Picolinic Acids; D011753:Pyrones; D017967:Zinc Compounds; D013912:Threonine; C008316:maltol; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; C030614:picolinic acid