Effect of hydrogen sulfide on airway inflammation induced by ozone in mice / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the effect of hydrogen sulfide ( H2 S) on airway inflammation induced by ozone (O3) exposure and its mechanisms.METHODS:C57BL/6 mice (n=32) were randomly divided into control group, O3 group, NaHS+O3 group and NaHS group.The mice in O3 group and O3 +NaHS group were exposed to 2.14 mg/m3 O3 for 3 h on days 1, 3 and 5, while the mice in control group and NaHS group were exposed to filtered air .NaHS (14μmol/kg) was administered intraperitoneally to the mice in NaHS group and O 3 +NaHS group 30 min before each exposure .After the last exposure for 24 h, the airway responsiveness was determined , and bronchoalveolar lavage fluid ( BALF) was collected for counting inflammatory cells and measuring total protein concentration .The lung tissues were collected for observing the morphological changes with HE staining .The levels of interleukin-6 ( IL-6 ) , interleukin-8 ( IL-8 ) , malondialdehyde ( MDA) and NF-κB p65 protein in the lungs were determined .RESULTS: Compared with control group , the airway re-sponsiveness, inflammatory cells, protein concentration, inflammation score, levels of IL-6, IL-8, MDA and NF-κB p65 in O3 group increased significantly , but these in NaHS+O3 group decreased compared with O 3 group.CONCLUSION: The present findings suggest that H 2 S attenuates O3 induced airway inflammation by inhibiting NF-κB expression and preventing lipid peroxidation .

Expression of transient receptor potential canonical 1 in ozone-induced inflammatory lung tissues in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect the expression of transient receptor potential canonical 1 (TRPC1) in a mouse model of ozone-induced lung inflammation and explore its role in lung inflammation.</p><p><b>METHODS</b>In a mouse model of lung inflammation established by ozone exposure, the expression of TRPC1 in the inflammatory lung tissues was detected by RT-PCR, Wstern blotting and immunohistochemistry.</p><p><b>RESULTS</b>Compared to the control mice, the mice exposed to ozone showed significantly increased expression level of TRPC1 mRNA and protein in the inflammatory lung tissues (P<0.05). Immunohistochemistry showed increased TRPC1 protein expressions in the alveolar epithelial cells, bronchial epithelial cells, and inflammatory cells in the inflammatory lung tissues (P<0.05). The mRNA and protein expression levels of TRPC1 were positively correlated with the counts of white blood cells, macrophages, neutrophils and lymphocytes in the bronchoalveolar lavage fluid of the exposed mice (P<0.01).</p><p><b>CONCLUSION</b>TRPC1 may play a role in ozone-induced lung inflammation in mice.</p>

Synthesis and antitumor activity of A-ring modified hexacyclic analogues of camptothecin / 药学学报

Aim To improve the biological activity of A-ring modified analogues of camptothecin.Methods A-ring modified camptothecins were synthesized from 10-hydroxycamptothecin or 7-ethyl-10-hydroxycamptothecin (SN-38) in three or four steps. Their cytotoxicity was evaluated using MTT assay,and their in vivo antitumor activity against mouse liver cancer H22 was tested. Results Five hexacyclic camptothecins (6a, 6b, 6c, 7a and 7b) are target compounds, and ten camptothecin derivatives are new compounds. Conclusion The modification of a 1,4-oxazine-2-one ring fused with positions 9 and 10 of Aring will reduce the antitumor activity of camptothecins.

Anti-mutagenicity activity of dehydroepiandrosterone / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The chemopreventive activity and mechanism of dehydroepiandrosterone (DHEA) were studied.</p><p><b>METHODS</b>Model of 7, 12-dimethylbenz (alpha) anthracene (DMBA) induced breast carcinoma in Sprague-Dawley rats, uitra-violet (UV)-induced DNA damage and Salmonella mutation assay were used.</p><p><b>RESULTS</b>In DMBA-induced rat mammary tumor model, the rats were orally given daily DHEA for 2 weeks before DMBA and continued for 10 weeks after DMBA administration. The results showed significant inhibition of tumor development by DHEA. The incidence of mammary carcinoma also decreased significantly on daily dose of oral 25 mg/kg DHEA with the mean tumor volume per rat also remarkably reduced by 92%. Moreover, 25 mg/kg DHEA treatment could significantly increase the carcinoma latency for about 3.5 weeks as compared with the control. Using polymerase chain reaction (PCR) assay, in vitro 10(-9) mol/L DHEA showed significant inhibitory effect on UV-induced DNA damage by 90%. In Ames test, DHEA was found to decrease DMBA and benzo (alpha) pyrene-induced TA98 and TA100 His(+) revertants markedly and the number of Salmonella clones were significantly reduced by 53.2% and 73.0% on dose of 5 microgram DHEA/plate. It was also shown that in vitro 10(-7) mol/L DHEA could also effectively inhibit the G-6-PDH activity, which might play an important role in its chemoprophylaxis activities.</p><p><b>CONCLUSION</b>The results strongly prove that DHEA is a potent cancer chemoprophylaxis agent, which exhibits inhibitory potential on mutation and chemical carcinogen in vivo and in vitro.</p>