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Mitochondrial structure and function in CCl4-induced cirrhosis in the rat
S Krählenbühl1, J Reichen, A Zimmermann
1Department of Clinical Pharmacology, University of Berne, Switzerland.
Hepatology (Baltimore, Md.)
|September 1, 1990
Summary
Cirrhosis impairs liver mitochondrial function primarily due to reduced liver cell mass, not specific mitochondrial alterations. Enzyme activity per inner mitochondrial membrane area increases, potentially maintaining function despite cell loss.
Area of Science:
- Hepatology
- Mitochondrial Biology
- Cellular Physiology
Background:
- Cirrhosis is associated with impaired liver mitochondrial function.
- The specific causes of this impairment, whether reduced cell mass or intrinsic mitochondrial changes, remain unclear.
Purpose of the Study:
- To investigate the causes of mitochondrial dysfunction in cirrhosis.
- To differentiate between the effects of reduced hepatocellular mass and specific mitochondrial alterations.
Main Methods:
- Stereological analysis of mitochondrial volume and membrane surface density in control and cirrhotic rat livers.
- Induction of cirrhosis using phenobarbital and carbon tetrachloride (CCl4).
- Measurement of enzyme activities and oxygen consumption in isolated mitochondria and perfused livers.
Main Results:
- Hepatocellular and mitochondrial volumes were significantly reduced in cirrhotic rats.
- Total mitochondrial outer and inner membrane surface areas were decreased, but membrane surface per mitochondrial volume remained normal.
- Inner mitochondrial membrane enzyme content (cytochrome oxidase, ATPase) per unit area was increased.
- Basal oxygen consumption per gram of liver was reduced, but normalized when expressed per unit of inner membrane surface area.
Conclusions:
- Impaired mitochondrial function in cirrhosis is predominantly caused by a loss of hepatocellular mass.
- Increased enzyme activity per unit surface area of the inner mitochondrial membrane may play a compensatory role in maintaining liver function.