Differential action of methylselenocysteine in control and alloxan-diabetic rabbits.
Antidiabetic action of inorganic selenium compounds is commonly accepted. Since in diet selenium mainly exists as selenoamino acids, potential hypoglycemic properties of methylselenocysteine (MSC) were investigated in four groups of rabbits: untreated and MSC-treated control animals as well as alloxan-diabetic and MSC-treated diabetic rabbits. MSC (at a dose of 1mg/kg body weight) was administered daily for 3 weeks via intraperitoneal injection. The data show, that in MSC-treated control animals plasma glucose concentration was diminished, while plasma urea and creatinine levels as well as urine albumin content were elevated and necrotic changes occurred in kidney-cortex. Decreased GSH/GSSG ratios in blood, liver and kidney-cortex were accompanied by increased glutathione peroxidase and glutathione reductase activities and a diminished renal gamma-glutamylcysteine synthetase activity. Death of 50% of control animals was preceded by a dramatic decline in blood glucose concentration. Surprisingly, in MSC-treated diabetic rabbits, plasma glucose levels were either normalized or significantly decreased. Blood and liver GSH/GSSG ratios were increased and renal functions were markedly improved, as indicated by a diminished albuminuria and attenuated histological changes characteristic of diabetes. However, after administration of MSC to diabetic rabbits plasma urea and creatinine levels as well as renal GSH/GSSG ratios were not altered. In view of MSC-induced marked accumulation of selenium in kidneys and liver of control rabbits, accompanied by a decline in blood glucose level, disturbance of glutathione homeostasis and kidney-injury, application of MSC in chemotherapy needs a careful evaluation. On the contrary, MSC supplementation might be beneficial for diabetes therapy due to an improvement of both glycemia and renal function.
Kiersztan
Anna
A
Department of Metabolic Regulation, Institute of Biochemistry, Faculty of Biology, University of Warsaw, ul. Miecznikowa 1, 02-096 Warsaw, Poland.
Baranska
Anna
A
Hapka
Michal
M
Lebiedzinska
Magdalena
M
Winiarska
Katarzyna
K
Dudziak
Marta
M
Bryla
Jadwiga
J
D000419:Albuminuria; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009336:Necrosis; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010088:Oxidoreductases / Q000097:blood; D011817:Rabbits; D012643:Selenium / Q000032:analysis / Q000378:metabolism; D017279:Selenocysteine / Q000031:analogs & derivatives; D014508:Urea / Q000097:blood
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D016566:Organoselenium Compounds; D017279:Selenocysteine; D014508:Urea; D003404:Creatinine; D010088:Oxidoreductases; D012643:Selenium; D003545:Cysteine; C002979:selenomethylselenocysteine