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.