Intestinal enzyme activity in lambs chronically infected with Trichostrongylus colubriformis: effect of anthelmintic treatment.
After twenty weeks of continuous dosing with Trichostrongylus colubriformis larvae substantial, but declining, numbers of worms had persisted in most of the lambs examined, although there were wide inter-individual variations. Mucosal lesions were found in the proximal small intestines of all the infected animals, their severity being directly related to worm burden. Representative brush border enzyme activities analysed in intestinal mucosal extracts from the same lambs showed differing responses. Alkaline phosphatase and glycyl-L-leucine dipeptidase were significantly depleted, whereas maltase activity was only marginally reduced, and leucine aminopeptidase activity was normal. Mucosal acetylcholinesterase activity was significantly elevated in the parasitised animals and, interestingly in view of the postulated role of this enzyme in nematode pathogenicity, the level of activity was directly correlated with individual worm burdens. Intestinal trypsin and chymotrypsin activities were unaffected and the level of superoxide dismutase, an enzyme associated with the inflammatory response, was normal. There were also no consistent changes in the mucosal activities of several enzymes including lactic dehydrogenase, creatine phosphokinase, aldolase, and glutamic oxaloacetate transaminase, whose leakage from damaged or necrotic tissues has been well defined in terms of the concomitant increase in their activity in the circulation. Lambs treated orally with fenbendazole five and/or ten weeks before slaughter either in the presence or absence of continued larval intake, had negligible worm burdens, and showed little evidence of intestinal damage at post mortem. Brush border enzyme levels, with the exception of alkaline phosphatase and, in two cases dipeptidase, were normal in these animals. The activity of alkaline phosphatase was approximately double that in the continuously infected, untreated lambs, but remained markedly lower than in the uninfected controls. The activities of the other enzymes studied, including acetylcholinesterase, were within the control range. In summary, in chronic trichostrongylosis even relatively low nematode burdens were associated with marked pathological and biochemical damage in the intestine with both lesion severity and mucosal acetylcholinesterase activity being directly related to worm numbers. Although morphological integrity was completely restored after anthelmintic treatment, the persistent low activity of brush border alkaline phosphatase coupled with the enzymological findings in untreated, infected animals suggests that recovery of the full functional capability of the intestinal mucosa may take longer.
D000110:Acetylcholinesterase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D004150:Dipeptidases / Q000378:metabolism; D005260:Female; D005273:Fenbendazole / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000201:enzymology*; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000201:enzymology; D012756:Sheep; D012757:Sheep Diseases / Q000201:enzymology*; D014252:Trichostrongyloidiasis / Q000188:drug therapy / Q000201:enzymology / Q000662:veterinary*; D000520:alpha-Glucosidases / Q000378:metabolism
D001562:Benzimidazoles; D005273:Fenbendazole; D000110:Acetylcholinesterase; D000469:Alkaline Phosphatase; D000520:alpha-Glucosidases; D007931:Leucyl Aminopeptidase; D004150:Dipeptidases; C020825:cytosol non-specific dipeptidase