Effects of Calcium Dobesilate on Adrenomedullin, Nitric Oxide and Superoxide Dismutase Levels in Experimental Stress Ulcer Formation

Abstract

Objective: In the present study, we investigated the adrenomedullin (AM) and total nitric oxide (NOx) [nitrite plus nitrate] levels in experimentally induced stress ulcer model in rats. To examine the relation with oxidative stress, we measured the levels of thiobarbituric acid-reactive substances (TBARS) as an index of lipid peroxidation, and superoxide dismutase (SOD) activity together with the effect of calcium dobesilate (Ca-D) as well. Material and Methods: In this study, 33 female Wistar-Albino rats weighing about 230 g (200-250) aged 7-8 months were used. The rats were divided into 3 groups each containing 11 rats. The Ca-D-treated stress group received daily single oral dose of calcium dobesilate for 10 days (group 1). The saline-treated stress group received daily single oral dose of saline (same volume with calcium dobesilate) for 10 days (group 2). The non-stressed control group received daily single oral dose of saline (same volume with calcium dobesilate) for 10 days (group 3). In all groups of rats, plasma AM, NOx and TBARS levels as well as gastric mucosa NOx, TBARS levels. and SOD activity were determined. Results: In group 2 plasma AM (p< 0.001), plasma NOx (p< 0.001), gastric mucosa NOx (p< 0,001), and gastric mucosa TBARS levels (p< 0.01) were significantly higher than the levels in the control group. In group 1, elevated plasma NOx, gastric mucosa NOx, and plasma TBARS levels were found compared to the control group. On the other hand, the average plasma adrenomedullin and gastric mucosa TBARS levels in group 2 were significantly higher (p< 0.001) and plasma NOx levels were lower (p< 0.01) compared to group 1. In addition, in group 1 and 2, decreased SOD activity (p< 0.001) was found in gastric mucosa compared to the control group. Conclusion Elevated levels of AM and NOx may be generated to protect the organism as a response to increased oxidative stress. Calcium dobesilate may partially protect the organism against oxidative stress in stress ulcer pathogenesis, probably in relation to NO. However, further studies will be required to evaluate the role of calcium dobesilate in stress ulcer pathogenesis because of low levels of plasma AM and high levels of plasma TBARS in Ca-D-treated stress group.