L-carnitine inhibits hypoglycemia-induced brain damage in the rat.
Hypoglycemia sometimes occurs in patients with diabetes mellitus who receive excessive doses of insulin. Severe hypoglycemia has been known to induce mitochondrial swelling followed by neuronal death in the brain. Since L-carnitine effectively preserves mitochondrial function in various cells both in vitro and in vivo, we investigated its effects on the neuronal damage induced by hypoglycemic insult in male Wistar rats. Animals were given L-carnitine-containing water (0.1%) for 1 week and then received insulin (20 U/kg, i.p.) to induce hypoglycemia. Although L-carnitine did not affect the mortality of animals that developed hypoglycemic shock, it improved the cognitive function of the survived animals as assessed by the Morris water-maze test. L-carnitine effectively inhibited the increase in oxidized glutathione and mitochondrial dysfunction in the hippocampus and prevented neuronal injury. L-carnitine also inhibited the decrease in mitochondrial membrane potential and the generation of reactive oxygen species in hippocampal neuronal cells cultured in glucose-deprived medium. These results suggest that L-carnitine prevents hypoglycemia-induced neuronal damage in the hippocampus, presumably by preserving mitochondrial functions. Thus, L-carnitine may have therapeutic potential in patients with hypoglycemia induced by insulin overdose.
Hino
Kazuo
K
Department of Biochemistry and Molecular Pathology, Osaka City University Medical School, Osaka 545-8586, Japan.
Nishikawa
Manabu
M
Sato
Eisuke
E
Inoue
Masayasu
M
D000447:Aldehydes / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002232:Carbocyanines / Q000378:metabolism; D002331:Carnitine / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005947:Glucose / Q000172:deficiency; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D007003:Hypoglycemia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007328:Insulin; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors
D000447:Aldehydes; D001562:Benzimidazoles; D002232:Carbocyanines; D007328:Insulin; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; C022616:thiazolyl blue; D005978:Glutathione; D005947:Glucose; C027576:4-hydroxy-2-nonenal; D002331:Carnitine