Abstract:
Introduction. 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.
Purpose of the research. To study the protective effect of glutargin on the pancreas of rats with chronic pancreatitis induced by a blocker of NOs.
Material and methods. 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.
Results. 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.
Conclusions. 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.
