Integrative toxicopathological evaluation of aflatoxin B exposure in F344 rats.
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In this study, male F344 rats were orally exposed to a single dose of aflatoxin B (AFB) at 0, 50, 250, or 1,000 g/kg body weight (BW) or repeated dose of 0, 5, 10, 25, or 75 g/kg BW for up to 5 weeks. Biochemical and histological changes were assessed together with the formation of AFB1-lysine adduct (AFB-Lys) and liver foci positive for placental form glutathione S transferase (GST-P). In single-dose protocol, serum aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) showed dose-related elevation, with maximal changes observed (>100-fold) at day 3 after treatment. Animals that received 250 g/kg AFB showed concurrent bile duct proliferation, necrosis, and GST-P hepatocytes at 3 day, followed by liver GST-P foci appearance at 1 week. In repeated-dose protocol, bile duct proliferation and liver GST-P foci co-occurred after 3-week exposure to 75 g/kg AFB, followed by proliferation foci formation after 4 week and dramatic ALT, AST, and CK elevations after 5 weeks. Liver GST-P foci were induced temporally and in a dose-related manner. Serum AFB-Lys increased temporally at low doses (5-25 g/kg), and reached the maximum after 2-week exposure at 75 g/kg. This integrative study demonstrated that liver GST-P cells and foci are sensitive biomarkers for AFB toxic effect and correlated with bile duct proliferation and biochemical alterations in F344 rats.
author list (cited authors)
Qian, G., Wang, F., Tang, L., Massey, M. E., Mitchell, N. J., Su, J., ... Wang, J.
complete list of authors
Qian, Guoqing||Wang, Franklin||Tang, Lili||Massey, Michael E||Mitchell, Nicole J||Su, Jianjia||Williams, Jonathan H||Phillips, Timothy D||Wang, Jia-Sheng