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Zhuraeva Mohigul, Andijan State Medical Institute E-mail: mohigul_azimovna@mail.ru
THE INFLUENCE OF ^NTRYKAL ON THE CHANGE OF DIGESTIVE HYDROLASES OF THE STOMACH AND PANCREAS IN SUBACUTE POISONING WITH CARBON TETRACHLORIDE
Abstract: In the article "the effect of contrykal on the change of digestive hydrolases of the stomach and pancreas in subacute carbon tetrachloride poisoning" the data of scientific research conducted on 30 rats in 3 series of 10 rats. In 1 series (control) saline solution was administered for 21 days. In 2 series (experimental) on the model of subacute poisoning, CCl4 was injected for 21 days. 3 series (experienced) in the model of subacute poisoning with CCl4, and in the second group, but further intraperitoneally injected protease inhibitor contrykal daily since 15 days. It was found that under the influence of acute poisoning of CCl4 increases the activity of the pancreas, while reducing the activity of the stomach glands. The use of contrykal on the background of poisoning with CCl4 contributes to the decrease in the activity of the pancreas, with a simultaneous increase in the activity of the gastric glands.
Keywords: contrykal, pancreas, activity of gastric glands.
30 rats in 3 series of 10 rats. In series 1 (control), physi- The results ofthe study ofthe physiological role ofcholecys-
ological saline was injected for 21 days. In series 2 (experi- tokinin as a regulator ofgastrin secretion show that postprandial
mental), CCl4 was injected on a model of sub-acute poisoning for 21 days. In series 3 (experimental) on the model of subacute poisoning CCl4, as in the second group, only an additional intraperitoneal injection of the protease inhibitor specific daily began from day 15. It was found that under the influence of subacute poisoning CCl4 increases the activity of the pancreas, with a simultaneous decrease in the activity of the gastric glands. At the same time, the use of contrykal on the background of poisoning with CCl4 contributions to a decrease in the activity of the pancreas, with a simultaneous increase in the activity of the gastric glands.
It was found that in patients diagnosed with viral hepatitis levels of pancreatic enzymes of serum and pancreatic amylase and serum lipase levels increase with the progression of liver disease [4; 10; 16]. It was also determined that in patients with liver cirrhosis, the average rate of free and total acidity, as well as pepsinogen 1 in serum were lower than under normal conditions. While the concentration of serum gastrin and somatostatin in patients with liver cirrhosis was significantly higher. [12; 14; 6].
Works of our laboratory showed physiological metabolism by liver of low-molecular peptides, in particular, CCK-8 [1]. This is confirmed by a number of other researchers [8]. This metabolism can change significantly in liver diseases. It was found that CCK-8 is metabolized to a large extent in healthy individuals and to a lesser extent in patients with liver cirrhosis. Due to this, CCK-8 is not the main form of CCK in plasma in healthy subjects, but significantly increases in patients with liver cirrhosis [9].
secretion of gastrin depends on CCK-8 and supports the function of monitoring the feedback of gastrin secretion [15].
It has been shown that CCK-8 produced during food stimulation has an increasing inhibitory effect on the secretion of gastric acid and that this effect is mediated by somatostatin [11].
CCK-8 can play a crucial role in inhibiting the stimulation of gastric acid secretion and controls gastric acid, plasma gastrin and somatostatin secretion [11].
In experiments on dogs in our laboratory found that the joint, intraportal injection of trypsin with short-chain peptides, pentagastrin increases the activity of gastric enzymes, and CCK - 8 pancreas. At this joint, intraportal protease inhibitor contrykal with short-chain peptides pentagastrin reduced fermentability gastro and CCK-8 pancreas [1, 2].
In this regard, we believe that one of the regulatory mechanisms of the ability of the liver to dispose of short-chain pep-tides and in particular CCK-8 is carried out through the endocrine and through the portal system in the liver pancreatic proteases (trypsin, chymotrypsin) and proteasactive receptors type 2 (PAR-2) liver.
Thus, the use of protease inhibitors can enhance hepatic utilization of short-chain peptides, and in particular CCK-8 in chronic liver diseases ofvarious etiologies, and reduce CCK-8 in the blood. This can help to increase the acidity of gastric juice and significantly accelerate the rate of gastric emptying, which can be effective in atrophic gastritis, in addition to reducing pancreatic amylase, lipase and trypsin in the blood, which can be effective in chronic pancreatitis.
In addition, with joint pancreatitis and hepatitis, there is an increase in proteolytic activity in the blood and a decrease in antiproteolytic activity. On the one hand due to pancreatitis, and on the other hand, the presence of chronic inflammation of the liver, stomach and pancreas causes a violation of the balance in the system of proteolytic and antiproteolytic activity in the direction of increasing proteolytic activity and reducing antiproteolytic activity. Therefore, the use of protease inhibitor can also contribute to anti-inflammatory effects.
These assumptions are supported by studies where it was shown that in rats the use of gabexate-a synthetic low molecular weight protease inhibitor significantly reduced, increased serum transaminase levels and improved liver histology 24 hours after administration of carbon tetrachloride. Tumor necrosis factor a (TNF-a) and interleukin-1^ (IL-1^) significantly decreased in rats treated with gabexate compared to rats treated with saline. The use of gabexate also significantly improved survival after a lethal dose of CCl 4 from 0% to 20% [13].
In other studies, it was found that preoperative injection of gabexate significantly improved liver damage compared to other patients (group without gabexate). Postoperative serum transaminase levels decreased markedly due to the marked suppression of IL-6 levels in the blood during liver surgery. This was accompanied by a lower incidence of postoperative complications and a lack of mortality [7].
Purpose of research. On the model of subacute liver poisoning with carbon tetrachloride in rats, to study the effect of protease inhibitor contrykal on changes in the blood of CCK-8, gastrin-17 and digestive hydrolases of the stomach and pancreas, as well as in the composition of gastric mucosal homogenates and pancreas digestive hydrolases, and to justify the mechanisms of these changes.
Material and methods. The experiments were carried out on 30 white laboratory mongrel male rats weighing 180-220 g in 3 series of 10 rats. In 1 series (control) saline solution was injected to male rats orally every other day at the rate of 0.1 ml per 100 g of animal weight for 21 days. In 2 series (experimental)
on the model of subacute carbon tetrachloride poisoning. To do this, carbon tetrachloride brand XH (CCl4) was injected orally to male rats every other day, at the rate of 0.1 ml per 100 g of animal weight for 21 days. 3 series (experienced) in the model of subacute poisoning with carbon tetrachloride as in the second group, but further intraperitoneally injected contrykal protease inhibitor (Aprotinin) 25000/kg ATrE daily since 15 days. All rats on the 22nd day after serum decapitation were determined by IFA: pepsinogen-1 (PG1) (JSC "Vector-best", Russia), CCK-8 ("BCM Diagnostics", USA), gastrin-17 (G17) ("Biohit", Finland). Biochemical methods were used to determine amylase pancreatic (JSC "Vector-best", Russia) and lipase pancreatic ("HUMAN", Germany), as well as hepatic samples: alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin. In the composition of pancreatic tissue homog-enate, total proteolytic activity (TPA) was determined by spec-trophotometric method [5], amylase by photometric method [3] in descending starch color. The total proteolytic activity (TPA) was determined by spectrophotometric method in the composition of gastric mucosal homogenate [5].
The results were processed by the method of variation statistics with the calculation of mean values (M), their errors (m), and the reliability of the difference between the compared Student-Fisher values (t). The results were considered reliable at P < 0.05.
Results and discussion. The results of experiments in rats showed that in animals of the experimental group 2 as a result of subacute poisoning with carbon tetrachloride, there was a significant increase in liver samples: ALT, AST, total bilirubin, compared with those of the control group (table).
At the same time, as a result of subacute poisoning with carbon tetrachloride, the degree of change in the hydrolases of the stomach and pancreas in the blood was noted in different directions. Pancreatic amylase and pancreatic lipase significantly increased in relation to the control group. At the same time, pepsinogen-I indices significantly decreased in relation to the control group (table).
Table 1.
Serum markers Controlled 1st group Practised 2 nd group Practised 3 rd group
1 2 3 4
Liver experiments
ALT (mmol/h*l) 0.56 ± 0.08 1.07 ± 0.1* 0.71 ± 0.08**
AST (mmol/h*l) 1.07 ± 0.13 1.93 ± 0.17* 1.35 ± 0.14**
General billirubine (mkmol/l) 3.9 ± 0.5 9.2 ± 1.2* 6.3 ± 0.4**
Hydrolase of blood
Pancreatic amylase 63.1 ± 7.9 123.6 ± 13.1* 86.5 ± 9.1**
Pancreatic lipasa 42.6 ± 5.3 94.2 ± 8.6* 69.8 ± 5.7**
Pepsinogen-I (mkg/l) 69.4 ± 8.6 32.5 ± 4.1* 41.3 ± 4.8
1 2 3 4
Peptids
CCK-8 ng/ml 0.87 ± 0.11 1.63 ± 0.15* 1.17 ± 0.11**
Gastrin-17 pmol/l 7.3 ± 0.92 15.9 ± 1.6* 12.5 ± 1.3
Hydrolase of homogenates
Amilasa of pancreatic gland ed/100mg 4892.5 ± 543.7 7362.5 ± 781.9* 6927.4 ± 725.3
Table 2. - Changes in the considered parameters in rats with subacute carbon tetrachloride poisoning
TPA of gastric gland ed/100 mg 649.5 ± 59.4 895.3 ± 82.4* 789.5 ± 82.6
TPA of gastric gland Ed/100 mg 87.5 ± 7.6 56.8 ± 5.1* 71.9 ± 6.2
* - significantly different values relative to the indicators of the control group; - significantly different values relative to the indicators of the experimental group 2
In the main group there was a significant increase in the blood composition of CCK-8 and Gastrin-17 compared with the control group.
As part of the homogenates of the gastric mucosa and pancreatic tissue indicators of digestive hydrolases, under the influence of acute carbon tetrachloride poisoning correlated with those of the blood. So significantly increased relative to the control group in the composition of pancreatic tissue ho-mogenate amylase and TPA. At the same time, pepsinogen-I indices in the composition of gastric mucosal homogenate significantly decreased in relation to the control group.
The experiments in rats in the 3 experimental groups showed that in animals the use of contrykal against the background of subacute carbon tetrachloride poisoning, there was a significant decrease in liver samples: ALT, AST, total bilirubin, compared with those in the 2nd experimental group (table).
As a result of the use of contrykal, against the background of subacute carbon tetrachloride poisoning, the indices of digestive hydrolases of the pancreas, pancreatic amylase and lipase in the blood significantly increased in relation to those data of the 2 experimental groups. At the same time, there was no significant increase in pepsinogen-I in relation to the 2nd experimental group (table).
At the same time, in the 3 experimental group there was a significant increase in the blood composition of CCK-8 and no significant decrease in Gastrin-17 compared to the 2nd experimental group (table).
Under the influence of the contrycal against the background of acute carbon tetrachloride poisoning, the indices of digestive hydrolases in the composition of the homogenates of the gastric mucosa and pancreatic tissue of the 3 experimental groups had no significant changes compared to the 2nd group, but correlated with those blood parameters.
The presented data demonstrate that in rats under the influence of acute carbon tetrachloride poisoning, an increase in the blood levels of amylase and lipase indicates an increase in
the functional activity of the pancreas, which is also confirmed by an increase in the composition of pancreatic tissue homogenate amylase and TPA, as well as CCK-8. At the same time, a decrease in pepsinogen-1 in the blood and an increase in gastrin-17 indicators indicate a decrease in the function of the digestive glands of the stomach, which is confirmed by a decrease in TPA in the composition of gastric mucosal homogenate.
The reason for these changes is the marked increase in the concentration of CCK-8 in the blood, which is the result of a decrease in its utilization in the liver, under the influence of acute poisoning with carbon tetrachloride [9]. Due to the fact that the physiological role of CCK-8 is to stimulate pancreatic secretion [14], due to this, there is an increase in the indicators taken into account. At the same time, the increase in CCK-8 in the blood reduces the secretion of gastric acid. Since CCK-8 plays a crucial role in inhibiting stimulated secretion of gastric acid, changing the content of gastrin in blood plasma and somatostatin secretion [11].
In experiments in rats with the injection of contrykal against the background of subacute carbon tetrachloride poisoning, a decrease in the blood levels of amylase and lipase indicates a decrease in the functional activity of the pancreas, which is confirmed, although not a significant decrease in the composition of the pancreatic tissue homogenate amylase and TPA, as well as a marked decrease in CCK-8. At the same time, although not a significant increase in blood pepsinogen-1 and a slight decrease in indicators gastrin-17, as well as an increase in TPA in the composition of gastric mucosal homogenate, may indicate an increase in the function of the digestive glands of the stomach.
These changes are associated with a decrease in the concentration of CCK-8 in the blood and are the result of increased utilization of it in the liver, under the influence of contrykal on the background of acute carbon tetrachloride poisoning [9]. Due to the fact that the physiological role of CCK-8 is to stimulate pancreatic secretion [14], due to this, there is a decrease in the parameters taken into account. At the same time, a decrease in
CCK-8 in the blood reduces the secretion of gastric acid. Since CCK-8 plays a crucial role in inhibiting stimulated secretion of gastric acid, changing the content of gastrin in blood plasma and somatostatin secretion [11].
Thus, under the influence of acute carbon tetrachloride poisoning increases the functional activity of the pancreas, while reducing the functional activity of the digestive glands of the stomach. At the same time, the use of contrykal against the background of carbon tetrachloride poisoning reduces the functional activity of the pancreas, while increasing the functional activity of the digestive glands of the stomach, thereby contributing to the restoration of the activity of both the pancreas and the stomach.
We believe that the participation of the liver in the utilization of CCK-8 can be considered as an additional physiological modifying factor in the peptidergic mechanisms ofregulation of the digestive glands, and in chronic hepatitis and cirrhosis ofthe liver is the main pathogenetic factor contributing to the development of these changes in the stomach and pancreas.
Conclusion. In toxic hepatitis, CCK-8 is the main factor contributing to an increase in the functional activity of the pancreas, and can contribute to the development of a hidden form of pancreatitis, while reducing the functional activity of the digestive glands stomach and lead to the development of a latent form of atrophic gastritis. The use of contrykal can help to restore functional activity of the pancreas and stomach.
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