RU2541739C1 - Method for simulating nsaid- pancreatopathy experimentally - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to experimental medicine and concerns simulating panctreatopathy caused by administering a non-steroidal anti-inflammatory drug (NSAID-panctreatopathy). The method involves the oral administration of Nise® into a laboratory rat in a single dose of 5 mg/kg of animal's body weight for 21 days.

EFFECT: method provides stimulating NSAID-panctreatopathy close to real clinical conditions, when using therapeutic doses of the preparation, leading to developing pathomorphological changes specific for a toxic drug-induced pancreatic injury.

3 ex

Description

The invention relates to experimental medicine, pathological physiology, gastroenterology, pharmacology and can be used to model pancreatic lesions induced by the use of non-steroidal anti-inflammatory drugs (NSAIDs) - NSAID pancreatopathy.

The following reproduction options are known in an experiment in NSAID-induced pancreatic lesions (NSAID pancreatopathy). So, Zhang W. et al., 2010, propose to model NSAID pancreatopathy by oral or intraperitoneal administration of naproxen at a dose of 20 and 40 mg / kg for 3 weeks, which leads to the formation of fibrous changes in the pancreas of animals [Zhang W., Gao J., Zhao T., Wu W., Bai Y., Zou D., Li Z. High-dose naproxen aggravates pancreatic fibrosis in a rat model of chronic pancreatitis // Pancreas. 2010 Apr; 39 (3): 293-300].

The prototype is an experimental model of Nasif W.A. et al., 2011, based on the administration of aspirin (acetylsalicylic acid) at a dose of 400 mg / kg (4 times the maximum therapeutic dose) to male Sprague-Dawley male rats for 21 days orally [Nasif WA ,, Lotey M., Mahmoud Mr Protective effect of gum acacia against the aspirin induced intestinal and pancreatic alterations // European Review for Medical and Pharmacological Sciences. - 2011; 15: 285-292]. The disadvantage of the model is that aspirin is currently rarely used in clinical practice in dosages necessary for the treatment of rheumatic pathology and relief of febrile syndrome, as well as the fact that when using aspirin, damage to the digestive tract - the mucous membrane of the stomach and small intestine - comes to the forefront with the formation of ulcers, which significantly distorts the picture of NSAID-associated pancreatic lesions in the experiment, since the pancreas suffers a second time with the development of gastric ita and enteritis due to the introduction of NSAIDs.

Effect: increasing the objectivity and accuracy of the method of modeling NSAIDs-pankeratopathy in the experiment.

This task is achieved by oral administration to non-linear white rats (males and females) of the Nise® non-steroidal anti-inflammatory drug (NSAID) - at a dose of 5 mg / kg of animal body weight once a day for 21 days.

Nise® (“Dr. Reddy's Laboratories Ltd.”, India, Hyderabad) - international nonproprietary name - nimesulide, chemical formula - 4′-nitro-2′-phenoxy-methane sulfonanilide, 100 mg tablets. Nise® is an NSAID in the sulfonanilide class. Selective inhibitor of COX-2 - an enzyme involved in the synthesis of prostaglandins - mediators of edema, inflammation and pain. The drug is used for rheumatoid arthritis, osteoarthritis, arthritis of various etiologies, arthralgia, myalgia, postoperative and post-traumatic pains, bursitis, tendonitis, algodismenorea, toothache, headache [Vidal Drug Reference: http://www.vidal.ru].

For modeling in an experiment, pancreatic lesions induced by taking non-steroidal anti-inflammatory drugs (NSAIDs-pancreatopathy) have not been previously used.

The method is as follows. A non-steroidal anti-inflammatory drug Nise® is administered orally for a laboratory animal (non-linear white rat) for 21 days in a single dose of 5 mg / kg of animal body weight. To do this, the Nise® tablet (100 mg nimesulide content) is divided in half, 50 mg is dissolved in 10 ml of pure distilled water, the result is a solution containing 5 mg of the substance in 1 ml, 4.0 ml of water is added to the resulting solution (the concentration of the solution is reduced 5 times); in the resulting solution of nimesulide contains 1 mg in 1 ml (dose of 5 mg / kg). Experimental animals are injected with 1.0 ml of the resulting solution.

Case Studies

Example 1. Rat, male, weight 246 g. An animal was administered orally daily in 1.0 ml of distilled water non-steroidal anti-inflammatory drug Nise® in a single dose of 5 mg / kg for 21 days. On the 22nd day, the animal was withdrawn from the experiment under ether anesthesia in compliance with the rules of euthanasia. Autopsy material was collected (pancreatic tissue - 10 samples) for histological examination.

Histological results: microscopic examination of the preparations in the pancreatic parenchyma revealed large areas of vacuole dystrophy of exocrinocytes and areas of necrosis with impaired acini structure, as well as degranulating mast cells. Binuclear cells were visualized on the periphery of necrosis zones. A flattening of the epithelium of intralobular and interlobular excretory ducts and fibrosis of their walls was noted. Hemodynamic disturbances were represented by plethora of blood vessels (veins).

Thus, in an experimental animal that was administered the non-steroidal anti-inflammatory drug Nise® in a single dose of 5 mg / kg for 21 days, pathomorphological changes characteristic of toxic drug damage to the pancreas were noted.

Example 2. Rat, female, weight 218 g. An animal was administered orally in 1.0 ml of distilled water for 21 days with a non-steroidal anti-inflammatory drug Nise® in a single dose of 5 mg / kg. On the 22nd day, the animal was withdrawn from the experiment under ether anesthesia in compliance with the rules of euthanasia. Autopsy material was collected (pancreatic tissue - 10 samples) for histological examination.

Histological results: in the pancreatic parenchyma, plethora of blood vessels was detected. In the pancreas tissue, different foci of exocrinocyte vacuole dystrophy, extensive foci of necrosis with regeneration — the appearance of a large number of binuclear cells, as well as protein masses and desquamated epithelial cells in the lumens of separate excretory ducts were found.

Therefore, in an experimental animal that was administered a non-steroidal anti-inflammatory drug Nise® in a single dose of 5 mg / kg for 21 days, pathomorphological changes characteristic of toxic drug damage to the pancreas were noted.

Example 3. Rat, male, weight 228 g. An animal was administered orally in 1.0 ml of distilled water for 21 days with a non-steroidal anti-inflammatory drug Nise® in a single dose of 5 mg / kg. On the 22nd day, the animal was withdrawn from the experiment under ether anesthesia in compliance with the rules of euthanasia. Autopsy material was collected (pancreatic tissue - 10 samples) for histological examination.

Results of a histological examination: with microscopy of the preparations, plethora of the blood vessels of the pancreas was noted. In the organ parenchyma, limited areas of protein (vacuole) exocrinocyte dystrophy with a violation of the acini structure, individual cells with fatty degeneration, fibrosis of the interlobular connective tissue and a large number of mast cells in it were revealed. Protein masses and desquamated epithelial cells were found in the lumens of individual excretory ducts; unquoted epithelial cells looked swollen.

Thus, in an experimental animal that was administered the non-steroidal anti-inflammatory drug Nise® in a single dose of 5 mg / kg for 21 days, pathomorphological changes characteristic of toxic drug damage to the pancreas were noted.

Claims (1)

A method for simulating NSAID pancreatopathy in an experiment by oral administration of a non-steroidal anti-inflammatory drug to laboratory rats, characterized in that Nize® is used as a non-steroidal anti-inflammatory drug in a single dose of 5 mg / kg of animal body weight, once a day, for 21 days.