Reduction of nutrient absorption in normal rats by cyclosporine.
The indications for using cyclosporine are expanding rapidly beyond immune suppression for transplantation. We have previously described reduced active glucose uptake by small bowel following CsA treatment in rats. This study examined the effect of varying the dose and route of administration of CsA on bowel function. Male Lewis rats were given CsA via subcutaneous injection at doses of 5 mg/kg or 30 mg/kg on alternate days, or orally via gavage at 0 (control solvent oil), 7.5 mg/kg, or 30 mg/kg daily. Weight gain and feed intake were followed for 1 month when a balance study was performed to quantify in vivo nutrient absorption from the feed. In vitro studies of glucose and fatty acid uptake studies were then performed. Weight gain was reduced by high-dose CsA whether given orally or by subcutaneous injection. Oral CsA reduced in vivo fat and energy absorption from the diet, and all doses and routes of administration of CsA caused a reduction in both active glucose uptake and passive fatty acid absorption by the bowel in vitro. Thus, CsA has significant effects on bowel function in the normal rat. We suggest that further studies are indicated to determine the effects of CsA in man, especially in conditions with already-impaired bowel function.
Sigalet
D L
DL
Surgical-Medical Research Institute, University of Alberta, Edmonton, Canada.
Kneteman
N M
NM
Thomson
A B
AB
D000818:Animals; D001772:Blood Cell Count; D002784:Cholesterol / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000097:blood; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew
D004573:Electrolytes; D005227:Fatty Acids; D016572:Cyclosporine; D002784:Cholesterol; D003404:Creatinine; D005947:Glucose