Molecular and histological responses in rat skin exposed to m-xylene

Solvents, surfactants, cutting fluids, hydrocarbons, and oils cause skin irritation by incompletely understood mechanisms. This study examined histological and molecular changes in rodent skin caused by brief topical exposures to m-xylene. At 0, 1, 2, 4, and 6 h after 1-h exposure, skin samples were removed and analyzed for histopathological changes and interleukin-1 alpha (IL-1 alpha) and inducible nitric oxide synthase (iNOS) protein levels. Histopathological changes (epidermal-dermal separation and granulocyte infiltration) and increases in IL-1 alpha and iNOS protein expression occurred during our observation period. IL-1 alpha levels increased by 80% immediately after exposure and iNOS levels increased about 60% 4 hours after exposure. Our study demonstrates that dermal exposure to m-xylene promotes IL-1 alpha and iNOS production in skin and these proteins may serve as early indicators of skin irritation.     

Flavones from Andrographis viscosula

Two new 2'-oxygenated flavones, 5,7,2'-trimethoxyflavone (1). and 5,7,2',4',6'-pentamethoxyflavone (2). were isolated from the whole plant of Andrographis viscosula along with three known flavones, echioidinin (3). 5,2',6'-trihydroxy-7-methoxyflavone (4). and echioidin (5). The structures of these compounds were elucidated on the basis of 1D and 2D NMR spectral studies.     

Flavonoids from Limnophila indica

Two flavonoids, (2S)-5,7,3',4'-tetramethoxyflavanone (1) and 5,7,2',5'-tetramethoxyflavone (2) together with three known flavonoids, 7-O-methylwogonin (3), skullcapflavone I (4) and 5-hydroxy-7,2'-dimethoxyflavone (5) were isolated from the whole plant of Limnophila indica. The structures of compounds 1-5 were elucidated on the basis of spectral and chemical studies.     

Flavonoids from Andrographis lineata

Three flavonoids, 5,7,2',3',4'-pentamethoxyflavone (1), 2'-hydroxy-2,4',6'-tri methoxychalcone (2) and dihydroskullcapflavone I (3), together with 17,19,20-trihydroxy-5beta, 8alpha H, 9beta H,10alpha-labd-13-en-16,15-olactone (4), a known diterpenoid and six known flavonoids, 5-hydroxy-7,8-dimethoxyflavanone (5), 5-hydroxy-7,8,2',3',4'-pentamethoxyflavone (6), 5,2'-dihydroxy-7-methoxyflavanone (7), 5,2'-dihydroxy-7,8-dimethoxyflavone (8), 5,2'-dihydroxy-7-methoxyflavone (9) and 5,2'-dihydroxy-7-methoxyflavone 2'-O-beta-D-glucopyranoside (10) were isolated from the whole plant of Andrographis lineata. The structures of these compounds were elucidated on the basis of spectral and chemical studies.     

Quercetin inhibits invasion, migration and signalling molecules involved in cell survival and proliferation of prostate cancer cell line (PC-3)

Urokinase-type plasminogen activator (uPA) is a serine protease that is involved in cancer progression, especially invasion and metastasis including prostate cancer. uPA activation is mediated by transactivation of uPAR and epidermal growth factor receptor (EGF-R) in prostate cancer progression. Prostate cancer (PC-3) cells have highly invasive capacity and they express uPA and uPAR gene. PC-3 cells are treated with quercetin, which inhibits invasion and migration of PC-3 cells. Quercetin downregulates uPA, uPAR and EGF, EGF-R mRNA expressions. Quercetin inhibits cell survival factor β-catenin, NF-κB and also proliferative signalling molecules such as p-EGF-R, N-Ras, Raf-1, c.Fos c.Jun and p-c.Jun protein expressions. But quercetin increased p38 mitogen-activated protein kinase protein expression. Our results suggest that quercetin inhibit migration and invasion of prostate cancer cells. It shows the value for treatment of invasive and metastasis type of prostate cancer.     

Effects of diallyl disulfide (DADS) on expression of apoptosis associated proteins in androgen independent human prostate cancer cells (PC-3)

Prostate cancer is a leading cause of death among the aging men. Surgical or radiotherapy is effective when the cancer is confined to the prostate gland but once the cancer spreads beyond the pelvis even chemotherapy and hormonal ablation therapy fails in curing this disease. Our previous studies have shown that diallyl disulfide (DADS) induces cell cycle arrest and also induces apoptosis in PC-3 cells. And now the present study is focused to see whether there is an activation of caspase cascade pathway. Hence, in the present study the apoptotic effect of DADS is studied by Western blot analysis of caspase-3, -9, -10 and Bcl-2, Bad, and Bax protein. The Apoptotic cells were assessed by Hoechst 33342 staining with 25 and 40 microM concentrations of DADS for 24 h. The results have shown that DADS at 25 and 40 microM concentrations has induced the activation of caspases. There is a significant increase in the expression of caspases (3, 9, and 10). The proapoptotic protein Bax has significantly increased at 40 microM of DADS treatment and there is significant increase of Bad protein at both the concentration. Bcl-2 protein has significantly decreased in DADS treated cells. Therefore, the present investigation serves as evidence that DADS may be a therapeutic drug in the treatment of prostate cancer.     

Dopamine-induced apoptosis is mediated by oxidative stress and Is enhanced by cyanide in differentiated PC12 cells

Dopamine (DA) oxidation and the generation of reactive oxygen species (ROS) may contribute to the degeneration of dopaminergic neurons underlying various neurological conditions. The present study demonstrates that DA-induced cytotoxicity in differentiated PC12 cells is mediated by ROS and mitochondrial inhibition. Because cyanide induces parkinson-like symptoms and is an inhibitor of the antioxidant system and mitochondrial function, cells were treated with KCN to study DA toxicity in an impaired neuronal system. Differentiated PC12 cells were exposed to DA, KCN, or a combination of the two for 12-36 h. Lactate dehydrogenase (LDH) assays indicated that both DA (100-500 microM) and KCN (100-500 microM) induced a concentration- and time-dependent cell death and that their combination produced an increase in cytotoxicity. Apoptotic death, measured by Hoechst dye and TUNEL (terminal deoxynucleotidyltransferase dUTP nick end-labeling) staining, was also concentration- and time-dependent for DA and KCN. DA plus KCN produced an increase in apoptosis, indicating that KCN, and thus an impaired system, enhances DA-induced apoptosis. To study the mechanism(s) of DA toxicity, cells were pretreated with a series of compounds and incubated with DA (300 microM) and/or KCN (100 microM) for 24 h. Nomifensine, a DA reuptake inhibitor, rescued nearly 60-70% of the cells from DA- and DA plus KCN-induced apoptosis, suggesting that DA toxicity is in part mediated intracellularly. Pretreatment with antioxidants attenuated DA- and KCN-induced apoptosis, indicating the involvement of oxidative species. Furthermore, buthionine sulfoximine, an inhibitor of glutathione synthesis, increased the apoptotic response, which was reversed when cells were pretreated with antioxidants. DA and DA plus KCN produced a significant increase in intracellular oxidant generation, supporting the involvement of oxidative stress in DA-induced apoptosis. The nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester and the peroxynitrite scavenger uric acid blocked apoptosis and oxidant production, indicating involvement of nitric oxide. These results suggest that DA neurotoxicity is enhanced under the conditions induced by cyanide and involves both ROS and nitric oxide-mediated oxidative stress as an initiator of apoptosis.