ISSN:
0006-3592
Keywords:
stress mediators
;
hepatocyte sandwich culture
;
factorial design
;
hepatocyte redox
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Process Engineering, Biotechnology, Nutrition Technology
Notes:
Stress mediators play a major role in inducing the hypermetabolic stress state in the liver after major injuries. The majority of studies on the effect of mediators on hepatocytes have focused on single factor effects or on the effect of very complex additives (e.g., serum), and there are no reports which have rigorously identified specific interactions between stress mediators. We used a factorial design experimental approach to evaluate the effects of a four to five day exposure to hormone (glucagon, hydrocortisone, and epinephrine) and cytokine [tumor necrosis factor-α (TNF-α) interleukin-1β (IL-1β) and interleukin-6 (IL-6)] stress mediators on stable cultures of rat hepatocytes. Both individual-factor effects and two factor interactions on the metabolism of urea, glucose, lactate, ketone bodies, albumin, and fibrinogen were evaluated. The cultured hepatocyte model exhibited physiologic responses to the applied stress mediators. While hydrocortisone and epinephrine had no effect, glucagon induced an increase in glucose and urea synthesis. Interleukin-6 increased fibrinogen and decreased albumin production. Furthermore, IL-6 and glucagon caused an increase in the ketone-body ratio (KBR = [acetoacetate]/[β-hydroxybutyrate]), which is in equilibrium with the intramitochondrial NAD+/NADH. Tumor necrosis factor-α and IL-1β, on the other hand, decreased the KBR. An important two-factor interaction between IL-1β and IL-6 was identified, namely that IL-1β effectively negates the positive effect of IL-6 on the KBR when both are present. These results provide further understanding of the effect of stress mediators on hepatic function and metabolism. These effects may have important implications in the pathogenesis of progressive organ dysfunction which often follows prolonged inflammatory states triggered by major injuries. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 58:222-230, 1998.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
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