title: Cytotoxicity of colchicine derivatives in primary cultures of human hepatocytes.
abstract: BACKGROUND
  Colchicine has been used to treat gout for centuries. However, owing to its toxicity it displays a variety of side effects. The replacement of colchicine by less toxic but still active derivatives would solve this drawback.
  
  
  OBJECTIVE
  The aim of this study was to examine the cytotoxicity of 17 colchicine derivatives.
  
  
  METHODS
  Primary cultures of human hepatocytes were the model of choice. Prior to testing, we measured the biochemical parameters of liver donors and the toxicological response of the hepatocytes cultures. For toxicity testing, cells were treated for 24 h with tested compounds in concentrations 1-100 microM. We monitored lactate dehydrogenase (LDH) leakage into the medium, mitochondrial activity (MTT test) and secretion of albumin.
  
  
  RESULTS
  Our data show that LDH and MTT were less sensitive parameters compared to albumin secretion for monitoring the toxicity of colchicine derivatives. Compounds with lower antimitotic activity displayed lowered toxicity.
  
  
  CONCLUSIONS
  Since human hepatocytes in culture are quiescent cells, they are not as susceptible to tropolone alkaloids as proliferating cells. Screening for colchicine derivatives with lowered cytotoxicity revealed that 10-O-demethylated compounds might be the substances of choice.
authors: Institute of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry Palacký University Olomouc, Hnevotínská 3, 77515 OLOMOUC, Czech Republic. moulin@email.cz
authors: Zdenek
authors: Z
authors: Dvorak
authors: Jitka
authors: J
authors: Ulrichova
authors: Roland
authors: R
authors: Weyhenmeyer
authors: Vilim
authors: V
authors: Simanek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003078:Colchicine / Q000031:analogs & derivatives / Q000633:toxicity*; D005260:Female; D006074:Gout Suppressants / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D006074:Gout Suppressants; D003078:Colchicine