Vitamin E inhibits renal mRNA expression of COX II, HO I, TGFbeta, and osteopontin in the rat model of cyclosporine nephrotoxicity.
BACKGROUND
In a rat model of cyclosporine (CsA) nephrotoxicity, vitamin E preserves renal function and reduces free radicals, vasoconstrictive thromboxanes, and tubulointerstitial fibrosis. We examined the effect of vitamin E on tubule gene expression in this model.


METHODS
In two of three groups, rats were treated with either CsA, or CsA plus vitamin E, whereas the control group received vehicles. We pooled purified tubules or whole kidney tissue in a novel manner to represent each treatment group, harvested RNA, and performed rigorously controlled qualitative reverse transcription-polymerase chain reaction.


RESULTS
Cyclooxygenase (COX) I mRNA was detectable in control animals, was increased by CsA, but was unchanged by vitamin E. COX II mRNA was detected in controls, was inhibited in the CsA group, and was further inhibited with vitamin E. Hemeoxygenase I and TGF-beta and osteopontin mRNA were increased in the CsA-treated group and were inhibited by vitamin E.


CONCLUSIONS
Our data support the involvement of free radicals, COX pathways, and pro-fibrotic genes in cyclosporine nephrotoxicity and suggest that the salutary effect of vitamin E involves the suppression of some of these genes.
Jenkins
J K
JK
Department of Medicine, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Huang
H
H
Ndebele
K
K
Salahudeen
A K
AK
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016572:Cyclosporine / Q000633:toxicity*; D004195:Disease Models, Animal; D015870:Gene Expression; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D007668:Kidney / Q000201:enzymology*; D007674:Kidney Diseases / Q000139:chemically induced*; D007684:Kidney Tubules / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D053495:Osteopontin; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D016212:Transforming Growth Factor beta; D053495:Osteopontin; D014810:Vitamin E; D016572:Cyclosporine; D006419:Heme Oxygenase (Decyclizing); D011451:Prostaglandin-Endoperoxide Synthases