The World's Most Odd YES1 Report

.. In the second part of the ROS production study, HeLa cells were exposed to different doses of melatonin in the presence of the medium dose of diquat (10 ��M) for 17 h. We found significant differences between treatment groups (F (6,12)=4.04, pProteases inhibitor in cells treated with diquat while the highest (100 ��M) and the two lowest (1 ��M and 0.1 ��M) concentrations of melatonin did not suppress this pro-oxidative effect of diquat. Treatment of cells with 10 ��M melatonin and 10 ��M diquat did not influence ROS production as compared to the control, indicating that melatonin in this concentration was able to suppress ROS production induced by diquat. Discussion Our results confirmed the expected negative effects of diquat on viability of Vero cells in the MTT test and were in line with our previous in vivo studies (Zeman et al., 2005). The finding that both melatonin and dihydromelatonin improved diquat deteriorated cell viability suggests that these negative effects were induced by ROS. The fact that bispyridyl herbicides induce ROS is well known (Bus et al., 1974), although only paraquat was studied in detail. Moreover, recent studies suggest specific toxic effects of diquat and paraquat on the cytoskeleton of cells through interaction between microfilaments and microtubules (Vismara et al., 2000). Based on these findings it can be hypothesized that protective effects of melatonin are manifested via multiple buy AZD9291 arrays of protection, including preserving microtubules and microfilaments and by their mutual interactions (King et al., 2005). Scavenging of ROS may be the prevalent mechanism and many published studies support antioxidative effects of melatonin (Galano et al., 2011, for a review). These data are in line with our results obtained in Vero cells after administration of moderate doses of melatonin. More surprisingly, in HeLa cells we found pro-oxidant action of melatonin especially in high concentrations. The pro-oxidative action has been less YES1 frequently documented in scientific literature. Melatonin was found to be well tolerated and non-toxic even in very high concentrations under in vivo conditions. Nevertheless, some studies indicated a pro-oxidative activity of melatonin under in vitro conditions (Zhang & Zhang, 2014, for a review). In all cases, the pro-oxidative effects were related to very high concentrations (10�C1000 ��M), while lower doses (