Activity of liver microsomal enzymes during the chronic phase of murine schistosomiasis

Abstract

The effects of schistosomiasis on microsomal enzymes were studied on post-infection day 90 when accumulated damage and fibrosis are most intense but granulomatous reaction around the eggs harbored in the liver is smaller than during the earlier phases. Swiss Webster (SW) and DBA/2 mice of either sex (N = 12 per sex per group) were infected with 100 Schistosoma mansoni cercariae on postnatal day 10 and killed on post-infection day 90. Cytochrome P-450 (CYP) concentration and alkoxyresorufin-O-dealkylases (EROD, MROD, BROD, and PROD), p-nitrophenol-hydroxylase (PNPH), coumarin-7-hydroxylase (COH), and UDP-glucuronosyltransferase (UGT) activities were measured in hepatic microsomes. Age-matched mice of the same sex and strain were used as controls. In S. mansoni-infected mice, CYP1A-and 2B-mediated activities (control = 100%) were reduced in SW (EROD: male (M) 36%, female (F) 38%; MROD: M 38%, F 39%; BROD: M 46%, F 19%; PROD: M 50%, F 28%) and DBA/2 mice (EROD: M 64%, F 58%; MROD: M 60%; BROD: F 49%; PROD: M 73%) while PNPH (CYP2E1) was decreased in SW (M 31%, F 38%) but not in DBA/2 mice. COH did not differ between infected and control DBA/2 and UGT, a phase-2 enzyme, was not altered by infection. In conclusion, chronic S. mansoni infection reduced total CYP content and all CYP-mediated activities evaluated in SW mice, including those catalyzed by CYP2E1 (PNPH), CYP1A (EROD, MROD) and 2B (BROD, PROD). In DBA/2 mice, however, CYP2A5-and 2E1-mediated activities remained unchanged while total CYP content and activities mediated by other CYP isoforms were depressed during chronic schistosomiasis. Correspondence

Evaluation of the genotoxicity of Orthosiphon stamineus aqueous extract

“…In the murine liver, BROD activity is mediated by cytochrome-P450 2B subfamily isoforms (i.e., CYP2B9 and CYP2B10) and as expected for mice, activity of these isoforms in females was slightly higher than that in males (Conte et al, 2007). Activity of EROD, a reaction catalysed by CYP1A subfamily isoforms, was slightly higher in males.…”

Chronic whipworm infection exacerbates Schistosoma mansoni egg-induced hepatopathology in non-human primates

“…The activity of the cytochrome P450 family of enzymes, which include CYP2E1 and CYP7A1, has been reported to be modulated by intestinal schistosomiasis, contingent on granulomatous reactions around the eggs in the tissue [10]. Chronic infection with S. mansoni in mice coincided with decreased levels of liver cytochrome P450 which correlate with fibrosis and progression of hepatopathology.…”

Schistosome infections induce significant changes in the host biliary proteome

“…Hepatic CYP, GST and UGT are three multigene families of enzymes that play a critical role in the metabolism of many drugs and xenobiotics [28][29][30]. It has been reported that the activities and levels of expression of these enzymes are altered by inflammatory stimuli, including helminthic infections [31]. In this sense, it has been shown that in chronic S. mansoni infection (late phase of schistosomiasis) the liver content and activity of some isoforms of CYP, GST and UDP are downregulated and these regulations seem to be associated with a greater induction of Th2 cytokines [32][33][34][35].…”