Effect of lead-exposed astrocytes on neuronal synaptic formation / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of lead-exposed astrocyte conditioned medium (ACM) on the synaptic formation of neurons and to provide reference for the mechanism of lead neurotoxicity.</p><p><b>METHODS</b>Astrocytes were cultured in the medium containing 50, 100, 200, 400, and 800 µmol/L lead acetate for 72 h. Alamar Blue was used to assess the cell viability of astrocytes, and then ACM was collected. Primarily cultured neurons were divided into six groups: pure culture group, non-glutamic acid (Glu)-induced ACM treatment group, Glu-induced lead-free ACM treatment group, and Glu-induced 50, 100, and 200 µmol/L lead acetate-exposed ACM treatment groups. Neurons were collected after being cultured in ACM for 24, 48, or 72 h. The content of synaptophysin (SYP) in neurons was determined by Western blot. The SYP expression in neurons was measured by immunofluorescence after being cultured in ACMfor 72 h.</p><p><b>RESULTS</b>In all lead-exposed groups, the cell viability of astrocytes declined with increasing concentration of lead (P < 0.05). The Western blot showed that compared with the pure culture group, the non-Glu-induced ACM treatment group and Glu-induced lead- free ACM treatment group had significantly increased content of SYP in neurons (P < 0.01); compared with the non-Glu-induced ACM treatment group, the Glu-induced ACM treatment groups had significantly reduced SYP expression in neurons (P < 0.05); compared with the Glu-induced lead-free ACM treatment group, all lead-exposed ACM treatment groups had the content of SYP in neurons significantly reduced with increasing concentration of lead after 72-h culture (P < 0.01), the 200 µmol/L lead-exposed ACM treatment group had significantly reduced content of SYP in neurons after 48-h culture (P < 0.01), and all lead-exposed ACM treatment groups showed no significant changes in the content of SYP in neurons after 24-h culture. Double-labeling immunofluorescence of SYP showed that all lead-exposed ACM treatment groups had a significant decrease in the number of SYP-fluorescent particles after 72-h culture (P < 0.05).</p><p><b>CONCLUSION</b>Astrocytes promote synaptic formation of neurons, which may be inhibited during lead exposure.</p>

Study of toxic effects on hearing, kidney and liver of mice induced by anticancer agent of cisplatin and their mechanisms / 中国药理学通报

AIM To establish an animal experimental model for study on prevention of cisplatin toxicity and explore the possible mechanisms of the toxicity induced by cisplatin administration. METHODS Cisplatin was administered i.p consecutively for five days to male mice weighted from 28 to 30 g. The toxic effects induced by different doses of cisplatin on hearing, liver and kidney were determined. RESULTS Dose dependent decrease of body weight, abnormality of kidney and liver coefficients, levels of BUN and activities of ALT in serum were induced by cisplatin administration. Furthermore, Levels of GSH, activities of GSH Px and SOD increased significantly in kidney. Reversely, levels of GSH, activities of GSH Px and SOD in liver decreased and levels of LPO increased significantly in animals given cisplatin compared with those in control animals. CONCLUSION Obvious damage on hearing, liver and kidney of mice could be induced after consecutively 5 days administration of cisplatin with doses range from 3 0 to 4 0 mg?kg -1 (body weight). Oxidative damage is one of the mechanisms of these toxic effects on liver and kidney induced by cisplatin. But for different organs or at different stages of cisplatin administration, the main mechanism may be different.