title: Mycelia glycoproteins from Cordyceps sobolifera ameliorate cyclosporine-induced renal tubule dysfunction in rats.
abstract: BACKGROUND
  Cordyceps sorbolifera has been used in Traditional Chinese Medicine for improving the renal function. Cyclosporine A (CsA) is an important immunosuppressive agent in the prevention of renal allograft rejection, but long-term usage of CsA could lead to chronic nephrotoxicity and renal graft failure. The study was aimed to investigate whether the mycelia glycoproteins of Cordyceps sobolifera (CSP) exert prevention effects on CsA-induced nephrotoxicity.
  
  
  METHODS
  Sprague-Dawley (SD) rats were randomly assigned into four groups (n=6 per group): normal saline (control group), CSP group, CsA group, and CSP-CsA group (CsA combined treatment with CSP). Glomerular and tubular functions were assessed and histological studies were performed.
  
  
  RESULTS
  CSP, prepared by hot water extraction, ethanol precipitation and membrane dialysis, was found to be composed of three glycoproteins with average molecular weights of 543, 31, and 6.3 kDa, respectively. CsA impaired urea clearance and creatinine clearance were significantly improved by concomitant administration of CSP. TUNEL histochemical stain revealed that CSP significantly decreased CsA-induced apoptosis in renal tubular cells. The reducing effect of caspase-3 activation by CSP was suggested through the over-expression of the anti-apoptosis protein Bcl-2 in renal tubule cells. In assessment of CSP protection of renal tubule function, we found that CSP restored CsA induced magnesium wasting by increasing the magnesium reabsorption channels TRMP6 and TRMP7.
  
  
  CONCLUSIONS
  The results suggested that CSP had a significant suppressive activity on CsA-induced apoptosis and protective activity against nephron loss possibly via its restoring activity by increasing the magnesium reabsorption channels TRMP6 and TRMP7 on CsA induced magnesium wasting.
authors.affiliation: Research Institute of Biotechnology, Hungkuang University, Taichung, Taiwan.
authors.forename: Charny-Cherng
authors.initials: CC
authors.lastname: Chyau
authors.affiliation: GrapeKing, Inc., Chung-Li, Taiwan.
authors.forename: Chin-Chu
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Research Institute of Biotechnology, Hungkuang University, Taichung, Taiwan.
authors.forename: Jun-Chang
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Division of Nephrology Kuan Tien General Hospital, Taichung, Taiwan.
authors.forename: Te-Cheng
authors.initials: TC
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Shu
authors.affiliation: Research Institute of Biotechnology, Hungkuang University, Taichung, Taiwan; Department of Nephrology, Taichung Veterans General Hospital, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. Electronic address: chc.ede@msa.hinet.net.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D032661:Cordyceps; D016572:Cyclosporine; D007166:Immunosuppressive Agents; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D025282:Mycelium; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D050053:TRPM Cation Channels / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D011134:Polysaccharides; D050053:TRPM Cation Channels; C507531:TRPM6 protein, rat; D016572:Cyclosporine; C486584:Trpm7 protein, rat
keywords: Cordyceps sobolifera; Cyclosporine A; Glycoproteins; Nephrotoxicity