Effect of tolbutamide, glyburide and glipizide administered supraspinally on CA3 hippocampal neuronal cell death and hyperglycemia induced by kainic acid in mice.
Sulfonylureas are widely used oral drugs for the treatment of type II diabetes mellitus. In the present study, the effects of sulfonylureas administered supraspinally on kainic acid (KA)-induced hippocampal neuronal cell death and hyperglycemia were studied in ICR mice. Mice were pretreated intracerebroventricularly (i.c.v.) with 30μg of tolbutamide, glyburide or glipizide for 10min and then, mice were administered i.c.v. with KA (0.1μg). The neuronal cell death in the CA3 region in the hippocampus was assessed 24h after KA administration and the blood glucose level was measured 30, 60, and 120min after KA administration. We found that i.c.v. pretreatment with tolbutamide, glyburide or glipizide attenuated the KA-induced neuronal cell death in CA3 region of the hippocampus and hyperglycemia. In addition, KA administered i.c.v. caused an elevation of plasma corticosterone level and a reduction of the plasma insulin level. The i.c.v. pretreatment with tolbutamide, glyburide or glipizide attenuated KA-induced increase of plasma corticosterone level. Furthermore, i.c.v. pretreatment with tolbutamide, glyburide or glipizide causes an elevation of plasma insulin level. Glipizide, but not tolbutamide or glyburide, pretreated i.c.v. caused a reversal of KA-induced hypoinsulinemic effect. Our results suggest that supraspinally administered tolbutamide, glyburide and glipizide exert a protective effect against KA-induced neuronal cells death in CA3 region of the hippocampus. The neuroprotective effect of tolbutamide, glyburide and glipizide appears to be mediated by lowering the blood glucose level induced by KA.
Department of Pharmacology, Institute of Natural Medicine, College of Medicine Hallym University, 39 Hallymdaehak-gil, Chuncheon 200-702, Gangwon-do, Republic of Korea.
Chea-Ha
CH
Kim
Department of Pharmacology, Institute of Natural Medicine, College of Medicine Hallym University, 39 Hallymdaehak-gil, Chuncheon 200-702, Gangwon-do, Republic of Korea.
Soo-Hyun
SH
Park
Department of Pharmacology, Institute of Natural Medicine, College of Medicine Hallym University, 39 Hallymdaehak-gil, Chuncheon 200-702, Gangwon-do, Republic of Korea.
Yun-Beom
YB
Sim
Department of Pharmacology, Institute of Natural Medicine, College of Medicine Hallym University, 39 Hallymdaehak-gil, Chuncheon 200-702, Gangwon-do, Republic of Korea.
Sung-Su
SS
Kim
Department of Pharmacology, Institute of Natural Medicine, College of Medicine Hallym University, 39 Hallymdaehak-gil, Chuncheon 200-702, Gangwon-do, Republic of Korea.
Su-Jin
SJ
Kim
Department of Pharmacology, Institute of Natural Medicine, College of Medicine Hallym University, 39 Hallymdaehak-gil, Chuncheon 200-702, Gangwon-do, Republic of Korea.
Su-Min
SM
Lim
Department of Pharmacology, Institute of Natural Medicine, College of Medicine Hallym University, 39 Hallymdaehak-gil, Chuncheon 200-702, Gangwon-do, Republic of Korea.
Jun-Sub
JS
Jung
Department of Pharmacology, Institute of Natural Medicine, College of Medicine Hallym University, 39 Hallymdaehak-gil, Chuncheon 200-702, Gangwon-do, Republic of Korea. Electronic address: hwsuh@hallym.ac.kr.
Hong-Won
HW
Suh
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D056654:CA3 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D005913:Glipizide / Q000008:administration & dosage / Q000494:pharmacology; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D006943:Hyperglycemia / Q000097:blood* / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D057967:Infusions, Intraventricular; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D014044:Tolbutamide / Q000008:administration & dosage / Q000494:pharmacology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D014044:Tolbutamide; D007608:Kainic Acid; D005905:Glyburide; D005913:Glipizide
Blood glucose; Glipizide; Glyburide; Kainic acid; Neuronal cell death; Sulfonylureas; Tolbutamide