Potential role of regucalcin as a specific biochemical marker of chronic liver injury with carbon tetrachloride administration in rats.

The potential sensitivity of liver specific protein regucalcin as a biochemical marker of chronic liver injury with carbon tetrachloride (CCl4) administration in rats was investigated. CCl4 (10%; 1.0 ml/100 g body wt) was orally given 5 times at 3-day intervals to rats, and the animals were killed by bleeding at 3, 6, 18, and 30 days after the first administration of CCl4. The body weight of rats was significantly lowered 3 and 6 days after CCI4 administration as compared with that of control rats administered with corn oil, and then the weight was restored at 18 and 30 days. Serum glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) activities were significantly increased 3 days after the administration, while a significant increase in serum y-glutamyltranspeptidase (gamma-GTP) activity was seen at 3 and 6 days after the administration. Serum GOT, GPT, and gamma-GTP activities were restored to control levels at 18 and 30 days after CCl4 administration. Serum albumin, alpha-fetoprotein, and ammonium levels were not changed by CCl4 administration. Meanwhile, serum regucalcin concentration was markedly increased 3 and 6 days after CCl4 administration, and a significant increase in serum regucalcin concentration was observed 18 and 30 days after the administration. Liver regucalcin mRNA and liver cytosolic regucalcin levels were significantly decreased 18 and 30 days after CCl4 administration. Liver content of calcium, which intracellular calcium homeostasis is maintained, was significantly increased between 3 and 30 days after CCl4 administration. Hepatic mitochondrial succinate dehydrogenase activity was significantly increased 30 days after the administration. The present study demonstrates that serum regucalcin has a potential sensitivity as a specific biochemical marker of chronic liver injury with CCl4 administration in rats.