Name: GERSICA DE ALMEIDA CORREIA SANTOS
Publication date: 27/09/2018
Advisor:
Name |
Role |
|---|---|
| EDUARDO HERTEL RIBEIRO | Co-advisor * |
| IVANITA STEFANON | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| EDUARDO HERTEL RIBEIRO | Co advisor * |
| IVANITA STEFANON | Advisor * |
| LÍVIA CARLA DE MELO RODRIGUES | Internal Examiner * |
Summary: INTRODUCTION: Organotins such as tributyltin (TBT) are environmental
contaminants with a cytotoxic effect. Animals chronically exposed to TBT have vascular reactivity dysfunction associated with increased production of reactive oxygen species (ROS). The aim of this study was to investigate the effect of a single exposure to TBT. Vascular reactivity of isolated female rat aorta rings was evaluated 24 hours after exposure to a single dose of TBT (500 ng / kg) per gavage. METHOD:
Wistar rats (240-260 g) were divided into control (CT) groups, and exposed to a single dose of TBT. The aorta was isolated and cut into rings, which were immersed in Krebs solution submitted to the concentration response curve of phenylephrine, LNG-nitroarginine methyl ester (L-NAME), Apocynine, Tiron and Losartan. The vasodilatory response was assessed by relaxing the increasing doses of
Acetylcholine (ACh). In addition, the presence of ROS was measured by the intensity of the fluorescence produced by the oxidation of the dihydroetide (DHE). Data were expressed as mean ± SEM and analyzed by 2-way ANOVA or unpaired t-test with significance of p <0.05. The protocols were approved by the Ethics Committee on Animal Experimentation UFES (Protocols 27/2016). RESULTS: The aortic rings from the TBT group showed reduction of sensitivity (pD2) and the maximum response (Rmax) to ACh (pD2 TBT: 6.37 ± 0.27 * vs CT: 7.3 ± 0.25; Rmax TBT: 77 ± 5,18 * vs. CT: 92.9 ± 1.88 *, * p <0.05 vs CT), and increased maximal response and phenilefrine sensitivity (Rmax: TBT: 142 ± 7.2 ** vs CT : 110 ± 4% KCl, ** p <0.01; pD2: TBT: 7.68 ± 0.08 * vs. CT: 7.19 ± 0.13% KCl, * p <0.05 vs. CT). A incubation of
the aortic rings with L-NAME increased the reactivity to phenilefrine in both groups (Rmax TBT: 142.2 ± 7.2 vs TBT L-NAME: 175 ± 7.8 # and CT: 110 ± 4 vs. CT LNAME: 165 , 7 ± 8.6 **% KCl, # p <0.05 vs TBT, ** p <0.01 vs CT). However, the area under the curve (dAUC %) was lower in the TBT vs CT group (CT: 52.4 ± 4.61 vs TBT: 35.8 ± 4.31 * p <0.05). The maximum response to phenilefrine was reduced in
the TBT group after incubation with Apocinin, Tiron, Catalase and Losartan (TBT: 142 ± 7.2 vs TBT APO: 102.9 ± 5.42 # # TBT TIRON: 104.3 ± 9, TBT: 101.8 ± 7.38 % KCl; # # p <0.01 vs TBT). ROS was increased in the aorta of the animals exposed to TBT. CONCLUSION: We conclude that 24 hours after exposure to a single dose of 500 ng / kg TBT causes endothelial dysfunction, increase in the vasoconstrictor
response to phenylephrine and a reduction in the vasodilatory response to acetylcholine that appears to be mediated by vascular oxidative stress.
