XXXV Reunião Anual da SBBqResumoID:8352


Oxidative Stress Induced by Helicobacter pylori in HeLa Cells is Responsible for Decreased Activity of Antioxidant Enzymes.

Gurgueira, S. A.; Miguel, F.; Augusto, A. C.; Ribeiro, M. L.; Mendonça, S. and Pedrazzoli Jr, J.



Unidade Integrada de Farmacologia e Gastroenterologia (UNIFAG), Universidade São Francisco, Bragança Paulista, SP, Brazil. E-mail: Sonia.Gurgueira@saofrancisco.edu.br.

Gastric diseases caused by H. pylori show increased ROS production that leads to tissue damage, different clinical settings and pathological outcomes, including chronic gastritis, peptic ulcer disease and gastric neoplasia. In this study, we evaluated the activity of the antioxidant enzymes MnSOD, GPX and CAT as well as aconitase and fumarase activities as oxidative stress markers in experiments of co-culture of HeLa cells (7x106 cells) and H. pylori 26695 (TIGR, genotype cagA+/ vacAs1m1/ iceA1). Our purpose was to determine the correlation of ROS production and H. pylori:HeLa cells ratio the activity of those enzymes. Our preliminary results showed that only H. pylori at a 500:1 ratio was able to significantly decrease aconitase activity (p < 0.05), but not fumarase activity, indicating an oxidative stress situation after 24h of incubation. At this ratio, H. pylori also caused a very significant decrease in total SOD (p < 0.001) and significant decrease in CuZnSOD (p < 0.05) but not in MnSOD activity. These effects on SOD activities were not observed using a 200:1 H. pylori ratio. However, this H. pylori concentration significantly decreased all GPX activities (p < 0.001) (total and selenium-dependent). CAT activity was very significantly decreased at either 200:1 or 500:1 H. pylori ratio. The 500:1 H. pylori ratio produced less than 5 mM of H2O2/ 24h. These results suggest that H. pylori decreases GSH concentration by lowering GPX activities, in a way that is dependent on the incubation time and on the H. pylori: HeLa cells ratio, leading to a ROS increase. This ROS increase also paralleled a decrease in CAT activity. In conclusion, H. pylori causes a chronicle subtle oxidative stress that is enough to decrease the main antioxidant enzymes defense and threatens DNA. The H. pylori:cell ratio and the time of this inflammatory situation can be an answer for differential disease outcome in different patients.

Supported by FAPESP (grant # 02/00835-0)