Monocyte aryl hydrocarbon hydroxylase (AHH) activity mimics Kupffer cell and hepatocyte AHH activity in an animal model of liver disease.
We have previously reported that monocyte aryl hydrocarbon hydroxylase (AHH) activity is depressed in patients with liver disease and is decreased more in cirrhosis than in early stage liver disease. To determine if monocyte AHH activity reflects liver AHH activity, we studied an animal model of cirrhosis, i.e., yellow phosphorus induced cirrhosis in the pig. AHH activity was detectable in monocytes isolated from peripheral blood of normal pigs (0.32 +/- 0.13 nmol.mg-1 P.h-1, n = 11) and was comparable to the level of AHH activity in hepatic Kupffer cells isolated from wedge or needle biopsies of livers of normal pigs (0.38 +/- 0.21, n = 7). The AHH level in pig Kupffer cells was approximately 10% of the AHH level in hepatocytes and microsomes. To induce liver disease, pigs were administered yellow phosphorus (0.6 mg/kg) 5 days per week for 16 weeks. At 4 weeks of treatment, monocyte AHH activity was not different from control and liver histology was normal. Depression of monocyte AHH activity was evident at 8 weeks of treatment when liver fibrosis was seen histologically. At 12 weeks of treatment when histology revealed extensive liver fibrosis and collagen levels were elevated, the level of monocyte AHH activity was decreased 67% compared with controls. Similar changes were observed at 12 weeks in Kupffer cell AHH activity (86% decrease) and hepatocyte AHH activity (70% decrease) compared with controls. These results suggest that monocyte AHH activity reflects liver AHH activity and may be a good indicator of change in liver enzyme function in liver disease in the pig model of cirrhosis.
Peterson
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TC
Department of Medicine, Dalhousie University, Halifax, N.S., Canada.
Williams
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CN
Malatjalian
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DA
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000172:deficiency / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007728:Kupffer Cells / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D008862:Microsomes, Liver / Q000201:enzymology; D009000:Monocytes / Q000201:enzymology*; D010758:Phosphorus; D013552:Swine
D010758:Phosphorus; D001189:Aryl Hydrocarbon Hydroxylases