5-DISCUSSION
Lysosomal acid hydrolases assisting lysosomes found in leukocytes in lungs in performing their duties are activated in acidic pH. The necessity of acidic pH for lysosomal hydrolases provides double protection against uncontrolled digestion of cytosol content. Even if the lysosomal membrane degrades, the released acid hydrolases will be inactive in the neutral pH of the cytosol. To preserve internal acidic pH, it is necessary for lysosomes to concentrate active H+ ions. The active transport of these ions into the cell is assisted by proton pumps in the lysosomal membrane. The most important effect mechanism in the struggle of leukocytes, especially neutrophil leukocytes, with bacteria is degradation and digestion of phagocytized bacteria with lysosome (Cooper., 2000). For degradation and digestion of bacteria within lysosomes, H2O2 must be formed within the lysosome and the H2O2 must later transform into HOCl acid.
The results of our study investigated preparations obtained with SOD, Gpx, MYP and catalase immunohistochemical staining of lung tissue and observed a significant degree of elevation in the PPI group compared to the control group in H-scores. The H2 receptor blocker of ranitidine (Ra) was not as effective as PPI; however, a significant increase was observed in the Ra group compared to the control group. Pictures obtained from groups with histochemical staining and toluidine blue staining showed increased infiltration in lung and histopathologic changes.
SOD is a 32 KDa hemodimeric metalloenzyme basically found in plasma, nuclei and cytosol (Chen., Watson et al., 2017). It catalyzes the separation of a catalytic copper ion and superoxide radical to dioxygen and hydrogen peroxide (H2O2). SOD also increases activity when the organism experiences increased oxidant stress. Especially in clinical situations with reduced effect of the antioxidant systems, SOD activity increases. In our study, in parallel with this information, SOD activity appeared to be increased in lung. The reason for the increase in SOD activity is the reduction occurring in oxidative stress, while we think another reason is catalysis of H2O2 formation expected to form in lysosomes. The changes in H2O2 amounts support this. The H2O2 amount obtained in the PPI group (35.67) was very low compared to the H2O2 amount obtained in the Ra group (88.67) and this was statistically significant. In both groups, in spite of histopathologic injury to the lungs, the statistically significant difference in H2O2 amounts found in lung tissue show that PPIs prevent sufficient formation of H2O2 in lysosomes found in neutrophils.
In our study, we saw significant degrees of elevation in SOD, CAT, MYP and Gpx activity in addition to antioxidant enzymes in the control group. A study by Rahimi et al. (Rahimi., Rakhshandeh et al., 2019) induced acute respiratory distress syndrome (ARDS) in rats and examined the anti-inflammatory and antioxidant activity of ‘Portulaca Olerecea’ extract and here they identified SOD, CAT and MYP activity increased after addition of Portulaca Olerecea extract. The researchers attempted to determine antioxidant enzyme levels with the aid of commercial kits using serum samples. A study by Hackert et al. examined the effects of pantoprazole on acute pancreatitis and in conclusion they saw inflammation was suppressed. The researchers concluded that pantoprazole had anti-inflammatory effects and reduced the progress of acute pancreatitis. The researchers examined MPO activity in studies and observed MPO activity increased with pantoprazole (Hackert., Tudor et al., 2010). However, a study from 6 years before in 2004 examined the in vivo anti-inflammatory properties of pantoprazole and concluded that it did not have anti-inflammatory features (Becker., Maróstica et al., 2004). The antioxidant enzyme activity was increased in the groups given PPI and Ra. The reason for this was not the increase in anti-inflammatory and antioxidant levels due to PPI and ranitidine, it is activation of the defense mechanism of the body against inflammation and oxidative stress induced by them. The result is an increase in the antioxidant levels in the body.
PPIs are the first medications chosen for treatment of diseases related to acid secretion. Long-term use is observed especially in situations like gastroesophageal reflux. Apart from this, we are against excessive prescriptions in unnecessary situations. In these situations, PPIs affect the lysosome and lysosomes will not be able to fulfil their duty to destroy bacteria and will cause increased lung infection.
In our study results, we saw the thesis related to the proliferation of bacteria linked to increased stomach pH and later pneumonia causing death, proposed as the reason for deaths occurring as a result of PPI use among patients in intensive care especially, was deficient. Our H2O2 results in lung tissue showed that lysosomal function disorder induced in neutrophil leukocytes in lung tissue worsened progression of disease.
In conclusion, PPIs do not just affect parietal cells found in the stomach. They may affect proton pumps in other tissues and cells in the organism. As a result, the use and indications for PPI should be reassessed considering more possible side effects than previously determined.