2 articles
Nitric oxide (NO) is a gaseous molecule that is a biological mediator that carries out important regulation of physiological processes necessary for the functioning of tissues. We hypothesized that nonspecific inhibition of all isoforms of NOs would cause pancreatic damage and created a model of experimental pancreatitis based on NOs inhibition. Along with the study of the mechanisms of development of chronic pancreatitis, the search for medicines to treat and inhibit the progression of this disease continues.
To study the protective effect of glutargin on the pancreas of rats with chronic pancreatitis induced by a blocker of NOs.
The work was carried out on 21 laboratory white male Wistar rats weighing 180-230 g. Chronic pancreatitis was induced by intraperitoneal administration of the NOs blocker - N-nitro-L-arginine (L-NNA) (Sigma-Aldrich, USA) at a dose of 40 mg/kg of body weight. Rats in group I (n = 7) were injected with L-NNA for 12 days, rats in group II (n = 7) were injected intraperitoneally with glutargin 20 mg/kg, after 20 minutes they were injected with L-NNA - within 12 days. Rats of the control group (n = 7) were injected intraperitoneally with 0.9% NaCl solution. The rats were euthanized on the 45th day and biochemical and morphological studies were carried out.
After the introduction of the NOs blocker, deterioration of the general condition of the animals was determined, a sharp increase in the level of nitrites/nitrates to 80.22±19.91 μmol/l, control 32.61±4.55 μmol/l (р < 0.05); protein-bound hydroxyproline (PBH) to 215.21±22.01μmol/l, control 178.67±26.39 μmol/l, (p < 0.05); free hydroxyproline (FH) to 14.74±1.84 μmol/l, control 9.96±0.71 μmol/l, (p < 0.05); malondialdehyde (MDA) to 5.67±0.88 nmol/ml, control 3.62±0.13, (р < 0.05). Pronounced structural changes with stasis of formed blood elements in the vessels, focal accumulation of leukocytes in the parenchyma, dystrophy of acinar cells and fibrosis in the atrophy zone were determined in the pancreas of rats. Administration of glutargin contributed to the restoration of general behavioral reactions of rats, normalization of MDA – 4.81±0.15 nmol/ml, control 4.50±0.23, (p > 0.05); ceruloplasmin (CP) – 591.71±68.07 mg/ml, control – 663.25±34.05 mg/ml, (p > 0.05); PBH 183.62±5.98 μmol/l, control – 179.28±9.19 μmol/l, (p > 0.05); FH – 9.44±1.13 μmol/l, control – 9.96±0.71 μmol/l, (p > 0.05) and prevented the development of pronounced structural changes in the pancreas.
In chronic pancreatitis induced by a NOs blocker, glutargin can prevent chronic pancreatitis by normalizing collagen metabolism, inhibiting oxidative stress, and severity of pancreatic parenchymal damage.
Chronic pancreatitis (CP) is a common disease with a complex pathogenesis, characterized by difficulties in its diagnosis and treatment.
To determine the main pathogenetic links of clinical and morphological forms of CP, markers of disease progression, to develop a diagnostic algorithm and principles of treatment of patients.
210 patients with CP were examined, who were divided into 4 groups: I - obstructive, II - calcifying, III - fibrous-parenchymal, IV – CP, complicated by pseudocyst. Instrumental, functional, morphological, biochemical, immunological, microbiological methods were used. To study the main morphological and biological changes in the pancreas during the development of CP and to study the effectiveness of the proposed treatment, we conducted experimental studies on 45 laboratory white Wistar male rats weighing 180-230 g.
Imbalance of the immune system, oxidative stress, toxic-metabolic disorders, and diseases of the biliary system are important in the development of various forms of CP. However, there are differences in the severity of these changes. The most pronounced activity of fibrotic processes in the pancreas is typical for patients with a long course of the disease and in the presence of complications (pseudocyst). The most unfavorable course and prognosis are seen in the calcifying form of CP. The markers of CP progression are the value of the calcification coefficient of 0.5-1.0, the translocation of DNase I from the cytoplasm to the nucleus of the acinar cell, the activation of collagen formation, the increase in the level of fibrosis activators (TGF-β1, TNF-a), and the intensification of lipid peroxidation processes. An early marker of apoptosis is the translocation of DNase I from the cytoplasm to the nucleus of an acinar cell.
The developed diagnostic algorithm allows assessing the pathophysiological features of functional and organic disorders of the pancreas, predicting the course of the disease and choosing the optimal treatment. The proposed treatment of patients with CP effectively reduces the severity of pain and oxidative stress, normalizes the cytokine profile, improves the general condition and quality of life of patients.