Adult rat liver slices as a model for studying the hepatotoxicity of vincaalkaloids

There are certain disadvantages associated with the use of isolated or cultured cells including the need to use proteolytic enzymes for their isolation and loss of tissue organization. In order to provide an in vitro system for toxicological studies that preserves tissue integrity, a method for preparation and incubation of adult rat liver slices has been developed. Fresh ultra-thin liver slices were produced in large quantities at a rapid rate under conditions that cause minimal tissue trauma. They were incubated in a system that has been designed to allow optimum gas and nutrient diffusion. Several biochemical parameters (lactate dehydrogenase (LDH) leakage, ATP content, protein synthesis and secretion) were monitored during a 20-hr incubation period. This liver slice model was used to study the toxicity of four vincaalkaloids: vincristine, vindesine, vinblastine and navelbine. Treatment with the vincaalkaloids resulted in an inhibition of protein synthesis and secretion without any effect on LDH leakage.