title: Norcantharidin ameliorates proteinuria, associated tubulointerstitial inflammation and fibrosis in protein overload nephropathy.
abstract: 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.
authors.affiliation: Division of Nephrology, Second Xiangya Hospital, Research Institute of Nephrology, Central-South University and Key Laboratory of Nephrology and Blood Purification in Hunan, Changsha, China.
authors.forename: Fu You
authors.initials: FY
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: You Ming
authors.initials: YM
authors.lastname: Peng
authors.forename: Kun
authors.initials: K
authors.lastname: Ye
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Liu
authors.forename: Shao-Bin
authors.initials: SB
authors.lastname: Duan
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Ling
authors.forename: Xiang-Qing
authors.initials: XQ
authors.lastname: Xu
authors.forename: Le-Tian
authors.initials: LT
authors.lastname: Zhou
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use*; D055513:Connective Tissue Growth Factor; D005355:Fibrosis / Q000097:blood / Q000188:drug therapy; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000097:blood / Q000188:drug therapy*; D011507:Proteinuria / Q000097:blood / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; C526317:CCN2 protein, human; C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D055513:Connective Tissue Growth Factor; C069741:norcantharidin