5-thio-D-glucose elevates renal transforming growth factor beta-1 at a dose that does not prevent streptozocine diabetes in rats.
Studies of early nephropathy in streptozocin (STZ)-treated rats are complicated by the nephrotoxicity of this agent. Inhibitors of the diabetogenic actions of STZ have been described, but their effects on the kidney have not been assessed. This study examined the effects of one agent, 5-thio-D-glucose (5TG) on renal hypertrophy and transforming growth factor beta1 (TGF-beta1). Forty male Sprague Dawley rats were divided into four groups: saline controls (SC), 5TG alone, 5TG + STZ, and STZ. After 2 weeks of observation, urine, plasma, and kidneys were studied. Nine of 10 STZ rats were diabetic at the time of euthanasia, as were 5 of 10 5TG + STZ animals. Both tissue levels of messenger RNA and protein for active and total TGF-beta1 were elevated in STZ and 5TG-STZ animals compared with SC. 5TG also elevated mRNA and produced protein levels intermediate to the other groups. 5TG plus STZ is an unacceptable control for nephropathy studies in STZ diabetes, both because of lack of efficacy at the dose studied and the induction of TGF-beta1 by 5TG. 5TG may yet prove of value in studying control of renal TGF-beta1 expression and excretion.
Lane
P H
PH
Department of Pediatrics, University of Nebraska Medical Center, Omaha 68198-2169, USA. phlane@unmc.edu
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005947:Glucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D001786:Blood Glucose; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C003002:5-thio-D-glucose; D005947:Glucose