Inherent toxicity of organ preservation solutions to cultured hepatocytes.
Organ preservation solutions have been designed to protect grafts against the injury inflicted by cold ischemia. However, toxicity of University of Wisconsin (UW) solution during rewarming has been reported. Therefore, we here assessed the toxicity of UW, histidine-tryptophan-ketoglutarate (HTK), Euro-Collins, histidine-lactobionate (HL), sodium-lactobionate-sucrose and Celsior solutions in cultured hepatocytes under hypothermic (4 degrees C), intermediate (21 degrees C) and physiological (37 degrees C) conditions. Marked toxicity of UW, HTK, HL and Euro-Collins solutions was observed at both 37 and 21 degrees C. With the exception of UW solution, these solutions also increased cell injury during cold incubation (LDH release after 18 h at 4 degrees C: HTK 76+/-2%, Euro-Collins 78+/-17%, HL 81+/-15%; control: Krebs-Henseleit buffer 20+/-6%). Testing of individual components using modified Krebs-Henseleit buffers suggested that histidine and phosphate are responsible for (part of) this toxicity. These potential toxicities should be taken into account in the development of future preservation solutions.
Rauen
Ursula
U
Institut für Physiologische Chemie, Universitätsklinikum, Hufelandstr. 55, D-45122 Essen, Germany. ursula.rauen@uni-duisburg-essen.de
de Groot
Herbert
H
D000241:Adenosine / Q000633:toxicity; D000493:Allopurinol / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D003080:Cold Temperature; D004187:Disaccharides / Q000633:toxicity; D004573:Electrolytes / Q000633:toxicity; D005947:Glucose / Q000633:toxicity; D005971:Glutamates / Q000633:toxicity; D005978:Glutathione / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects*; D006639:Histidine / Q000633:toxicity; D006982:Hypertonic Solutions / Q000633:toxicity; D007328:Insulin / Q000633:toxicity; D008297:Male; D008353:Mannitol / Q000633:toxicity; D019188:Organ Preservation Solutions / Q000633:toxicity*; D011189:Potassium Chloride / Q000633:toxicity; D011343:Procaine / Q000633:toxicity; D011887:Raffinose / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000633:toxicity
C039984:Bretschneider cardioplegic solution; C088453:Celsior; D004187:Disaccharides; D004573:Electrolytes; C037096:Euro-Collins' solution; D005971:Glutamates; D006982:Hypertonic Solutions; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D008353:Mannitol; D006639:Histidine; D011343:Procaine; D013395:Sucrose; D000493:Allopurinol; C005608:lactobionic acid; D011189:Potassium Chloride; D005978:Glutathione; D005947:Glucose; D000241:Adenosine; D011887:Raffinose