CHRONIC DIARRHEA AS A RESULT OF INTESTINAL MICROSPOSIDIOSIS IN A LIVER TRANSPLANT RECIPIENT

uent of the increased connective tissue in fibrotic processes (10). As seen in the bottom panel of Figure 2, steady state levels of osteopontin mRNA were easily detectable in controls and were increased in the tubule fractions from animals treated with CsA. Vitamin E also dramatically inhibited CsA-induced osteopontin mRNA (Figure 2, bottom panel). In summary, we have examined the effects of the antioxidant vitamin E on gene expression in the rat model of CsA nephropathy. Vitamin E significantly inhibits CsA-induced renal damage, including the tubulointerstitial fibrosis score and prostanoids (ref. 1 and this report). CsA induces the expression of COX I, HO I, TGFb, and osteopontin in vivo in the rat, and this expression is inhibited by concomitant treatment of the animals with vitamin E. COX II was also inhibited by vitamin E treatment, although we did not find that it was induced by CsA. Whereas the full scope of the mechanism of the renal effects of CsA are not yet known, they appear to include multiple arms of the vasoconstrictive, inflammatory, and fibrotic pathways. We have not yet determined the relative contribution of the various processes, but vitamin E appears to strongly affect fibrosis from CsA, regardless of whether the gene expression effects are direct or indirect. CsA nephrotoxicity is inhibited by the antioxidant vitamin E, which has a broad and specific effect on the pathologic processes initiated by CsA. Our findings suggest that vitamin E should be studied clinically as a possible preventative agent against the development of nephrotoxicity in those patients in whom CsA is prescribed.