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BACKGROUND: Lead can cause structural changes in the hippocampus, followed by damage to learning and memory functions, but its specific mechanisms are not yet clear. OBJECTIVE: To observe long-term toxicity of high-dose lead in drinking water on hippocampal tissue in rats, and analyze the potential association of oxidative damage, cell apoptosis, and pathology. DESIGN, TIME AND SETTING: A randomized, controlled animal experiment was performed at the Center for Medical Experiment, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA from May 2007 to October 2008. MATERIALS: Rabbit anti Bcl-2, Bax, and inducible nitric oxide synthase (iNOS) polyclonal antibodies were purchased from Santa Cruz Biotechnology, USA. An streptavidin-peroxidase immunohistochemistry kit and concentrated DAB kit were purchased from Beijing Zhongshan Biotechnology Company Limited, China. Crystal violet was purchased from Sigma, USA. METHODS: A total of 72 Wistar rats, aged 3 months, were randomly divided into control, low-, middle-, and high-dose lead groups, with 18 rats per group. Animal models were established through free drinking water contaminated by Pb2+ for 1, 3, and 6 months, respectively. MAIN OUTCOME MEASURES: The general toxicity of lead was dynamically observed; the levels of Pb2+ in the blood and brain tissue homogenate were detected using atomic absorption method; pathological changes were observed using hematoxylin-eosin staining and tigroid body staining; the protein expression levels of Bcl-2, Bax, and iNOS were dynamically observed using streptavidin-peroxidase immunohistochemistry of the hippocampus. RESULTS: Lead exposure reduced autonomic activities, produced a slumped appearance, slow responses, and lusterless fur, especially in the high-dose group. The amount of ingestion and hydroposia showed a decreasing trend, especially in middle- and high-dose groups. Lead levels in whole blood and brain homogenate were higher than controls (P < 0.01). Lead caused degeneration of hippocampal neurons and pyknosis, with fewer tigroid bodies, especially in high-dose lead group. Bcl-2 expression decreased with increasing lead dose (P < 0.01), whereas lead dose-dependently increased Bax levels (P < 0.01) and iNOS levels (P < 0.05). CONCLUSION: High levels of Pb2+ may disrupt hippocampal structure by passing through the blood brain barrier. Oxidative damage and apoptosis may be a toxicity mechanism of Pb2+ on the hippocampus.
BACKGROUND: Lead can cause structural changes in the hippocampus, followed by damage to learning and memory functions, but its specific mechanisms are not yet clear. OBJECTIVE: To observe long-term toxicity of high-dose lead in drinking water on hippocampal tissue in rats , and analyze the potential association of oxidative damage, cell apoptosis, and pathology. DESIGN, TIME AND SETTING: A randomized, controlled animal experiment was performed at the Center for Medical Experiment, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA from May 2007 to October 2008. MATERIALS: Rabbit anti Bcl-2, Bax, and inducible nitric oxide synthase (iNOS) polyclonal antibodies were purchased from Santa Cruz Biotechnology, USA. An streptavidin-peroxidase immunohistochemistry kit and concentrated DAB kit were purchased from Beijing Zhongshan Biotechnology Company Limited, China. Crystal violet was purchased from Sigma, USA. METHODS: A total of 72 Wistar rats, aged 3 months, were rando mly divided into control, low-, middle-, and high-dose lead groups, with 18 rats per group. Animal models were established through free drinking water contaminated by Pb2 + for 1, 3, and 6 months, respectively. MAIN OUTCOME MEASURES: The general toxicity of lead was dynamically observed; the levels of Pb2 + in the blood and brain tissue homogenate were detected using atomic absorption method; pathological changes were observed using hematoxylin-eosin staining and tigroid body staining; the protein expression levels of Bcl- Bax, and iNOS were dynamically observed using streptavidin-peroxidase immunohistochemistry of the hippocampus. RESULTS: Lead exposure reduced autonomic activities, produced a slumped appearance, slow responses, and lusterless fur, especially in the high-dose group. The amount of ingestion and hydroposia showed a decreasing trend, especially in middle- and high-dose groups. Lead levels in whole blood and brain homogenate were higher than controls (P <0.01). Lead caused degeneration of hippocampal neurons and pyknosis, with fewer tigroid bodies, especially in high-dose lead group. Bcl-2 expression decreased with increasing lead dose (P <0.01) and iNOS levels (P <0.05). CONCLUSION: High levels of Pb2 + may disrupt hippocampal structure by passing through the blood brain barrier. Oxidative damage and apoptosis may be a toxicity mechanism of Pb2 + on the hippocampus.