Norcantharidin (NCTD), the demethylated analog of
cantharidin isolated from Mylabris, is an anticancer
drug routinely used against various human
cancers in China. The aims of this study are to learn if NCTD has a protective action against severe
proteinuria and consequent interstitial
inflammation and
fibrosis, and if the inhibition of
nuclear factor-kappaB (
NF-kappaB) and
connective tissue growth factor (CTGF) by NCTD might be involved. Male Sprague-Dawley rats with
protein overload nephropathy induced by intraperitoneally injected
bovine serum albumin were used as a model. The histopathological examination of kidney tissue in the 9th week by light microscopy and scanning electron microscopy revealed that inflammatory cells had extensively infiltrated into the tubulointerstitial areas with interstitial
fibrosis. The administration of NCTD at 0.1 mg/kg/day to the
bovine-serum-albumin-injected animal models effectively reduced the
proteinuria, and prevented the
proteinuria-induced interstitial
inflammation and
fibrosis. Expressions of the
NF-kappaB p65 subunit and CTGF, detected by immunohistochemistry, Western blotting and reverse-transcription polymerase chain reaction, were upregulated in
protein overload nephropathy and were attenuated by NCTD. Inhibition of the expressions of the
NF-kappaB p65 subunit and CTGF was one beneficial effect of NCTD. These results suggest that in addition to the antiproteinuric action of NCTD, due to its anti-inflammatory and antifibrotic effects as shown in the present study, it may become a therapeutic agent for
proteinuria and its associated chronic inflammatory and fibrotic nephropathy.