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A Nutrient Mixture Suppresses Carbon Tetrachloride Induced Hepatic Toxicity in ICR Mice

M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050

Presented at: FASEB, San Francisco, CA, April 1-5, 2006

Published in: The FASEB Journal, Abstract 85

Abstract

Introduction:
Recent studies from our laboratory indicated that a unique nutrient formulation consisting of lysine, proline, ascorbic acid and green tea extract (NM) demonstrates a broad spectrum of pharmacological, therapeutic, cardiovascular and chemoprotective properties.

Objective:
We examined the effect of NM in mice treated with carbon tetrachloride (CT), a model of liver injury in which free radical, oxidative stress and cytokine production are closely linked.

Materials and Methods:
Six-week-old male ICR mice were divided into four groups of five animals each; Group A received corn oil and was used as a normal control. Group B mice received CT (25 ?L/kg, in corn oil, ip), group C mice were fed NM (0.5%) for two weeks, and group D mice were dosed with CT (25 ?L/kg, in corn oil, ip) after feeding NM (0.5%) for two weeks. All animals were sacrificed after 24 hrs. Blood was withdrawn by cardiac puncture and serum was collected for markers of liver and kidney. Liver and kidney were excised for histology

Results:
Administration of CT to group B mice resulted in marked increase in serum AST and ALT levels (markers for liver). Serum ALT and AST in groups A and C were of low magnitude and were comparable, whereas in group D animals these enzymes were significantly reduced. CT had no effect on renal markers (BUN, creatinine and BUN/creatinine ratio). CT administration caused an intense degree of liver necrosis that was less severe in the NM fed group D.

Conclusions:
These results indicate that NM could be a useful supplement in treating liver diseases due, in part, to its antioxidant properties and ability to scavenge CT-associated free radicals.

Comment:
Liver disease and toxicity is common, especially with many drug treatments. Carbon tetrachloride (CT)-induced liver injury in mice is an excellent model to evaluate the effectiveness of agents on inhibition or reversal of liver damage. A unique nutrient formulation consisting primarily of lysine, proline, ascorbic acid and green tea extract (NM) has demonstrated a broad spectrum of pharmacological, therapeutic, cardiovascular and chemoprotective properties. We examined the effect of a NM supplemented diet on liver and kidney tissue and serum markers in ICR mice dosed with CT. Administration of CT to mice on a regular diet resulted in marked increase in serum AST and ALT levels (markers for liver). In contrast, serum ALT and AST levels in NM-supplemented mice were of low magnitude and comparable to control mice (not dosed with CT). CT administration caused an intense degree of liver necrosis that was less severe in the NM fed group. These results are significant as they indicate that NM has potential in treating and preventing liver disease.


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