Oxidative stress arises from imbalance between generation of reactive oxygen species and anti-oxidant capacity of specific tissues. T
his alteration
has been correlated wit
h some disorders in pregnancy, mainly wit
h pre-eclampsia (PE). In PE, placental oxidative stress contributes wit
h t
he intense inflammatory response of t
he disease and supposed pat
hways related to t
his alteration include t
he formation of Inflammasome complexes t
hat mediate t
he maturation of pro-inflammatory cytokines.<
h4 id="absSec_2">Objectives
h4>
This study aims to evaluate if the treatment of placental explants with hydrogen peroxide (H2O2) is able to induce inflammasome complexes in placentas from normotensive pregnant women and then increase inflammatory cytokines expression.
<
h4 id="absSec_3">Met
hods
h4>
Placental explants were obtained from normotensive pregnant women undergoing elective cesarean section at 39 gestational weeks (N = 10). Placental explants were cultured in different concentrations of H2O2 (10, 100, 1000, 2000 and 10,000 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M) for 4 h. Explant controls were cultured only supplemented medium. Gene expression for cytokines (IL-1hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si2.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=012ce8a66e9d5aeb8613ad78934abea8" title="Click to view the MathML source">βhContainer hidden">hCode">h altimg="si2.gif" overflow="scroll">hvariant="normal">βh>, IL-10 and TNF-hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si3.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=ad7660aa9ef9ed0a8a41d1e7da7c68a8" title="Click to view the MathML source">α)hContainer hidden">hCode">h altimg="si3.gif" overflow="scroll">αhy="false">)h> and Caspase-1 were determined by RT-qPCR. Differences between groups were analyzed by non-parametric tests with significance level set at 5%.
<
h4 id="absSec_4">Results
h4>
Explants cultured with 1000, 2000 and 10,000 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M of H2O2 showed lower IL-10 mRNA expression than controls. On the contrary, higher gene expression of TNF-hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si5.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=7e36cc5d846f61e969a232bce69ead92" title="Click to view the MathML source">αhContainer hidden">hCode">h altimg="si5.gif" overflow="scroll">hvariant="normal">αh> was observed in the same concentrations. Interestingly, IL-1hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si2.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=012ce8a66e9d5aeb8613ad78934abea8" title="Click to view the MathML source">βhContainer hidden">hCode">h altimg="si2.gif" overflow="scroll">hvariant="normal">βh> mRNA expression was higher in the presence of 10 and 100 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M H2O2 concentrations than in 10,000 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M. IL-1hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si2.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=012ce8a66e9d5aeb8613ad78934abea8" title="Click to view the MathML source">βhContainer hidden">hCode">h altimg="si2.gif" overflow="scroll">hvariant="normal">βh> mRNA expression was also higher in cultures with 100 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M H2O2 concentration than in 1000 and 2000 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M. Gene expression of Caspase-1 was increased in cultures with 100 hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si1.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=53502f4b44036f2e4e8ead1fb560c622" title="Click to view the MathML source">μhContainer hidden">hCode">h altimg="si1.gif" overflow="scroll">hvariant="normal">μh>M of H2O2 concentration.
<
h4 id="absSec_5">Conclusion
h4>
These results suggest that the oxidative stress caused by H2O2 can activate caspase-1 wich participates in inflammasomes pathway and consequently increases the release of pro-inflammatory cytokines, such as IL-1hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si2.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=012ce8a66e9d5aeb8613ad78934abea8" title="Click to view the MathML source">βhContainer hidden">hCode">h altimg="si2.gif" overflow="scroll">hvariant="normal">βh> and TNF-hmlsrc">hImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S2210778916302227&_mathId=si5.gif&_user=111111111&_pii=S2210778916302227&_rdoc=1&_issn=22107789&md5=7e36cc5d846f61e969a232bce69ead92" title="Click to view the MathML source">αhContainer hidden">hCode">h altimg="si5.gif" overflow="scroll">hvariant="normal">αh>. In addition, different responses among different concentrations of H2O2 raise the importance of the oxidative stress intensity for pathological process. Financial support – FAPESP 2014/25611-5.