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Usmanova Shakhnoza Erkinovna, Independent researcher of Tashkent Medical Academy,
Republic of Uzbekistan Yakubov Abdujalol Vahabovich, Head of the department of Clinical Pharmacology of Tashkent Medical Academy, Republic of Uzbekistan
Hamraev Abror Asrarovich, professor, of the department of Internal Medicine № 2 of Tashkent Medical Academy Republic of Uzbekistan
E-mail: evovision@bk.ru
STATE OF COLLAGEN SYNTHESIS IN GASTRIC MUCOSA AND RENAL TISSUE IN INDOMETACIN GASTROPATHY IN ANIMALS WITH EXPERIMENTAL RHEUMATOID ARTHRITIS
Abstract: Production and release of aldosteron, proximal canalicular re-absorption of sodium, shortening of afferent and efferent arterioles, heightened saline appetite, inhibition of parasympathetic nervous system, stimulation of ^-adrenoreceptors, intensification of proteinuria - it is not complete list of effects provoked by angiotensin II. Mechanisms considered prove involvement of both glomerular and tubular-interstitial apparatus in damage of kidneys by indometacin.
Keywords: Collagen, indometacin gastropathy, rheumatoid arthrit.
It was established that reparation of ulcer defect heals Experimental model of rheumatoid arthritis was re-
by cicatrization. Main element of cicatricial tissue is colla- produced by a single administration of 0.2 ml Freund's gen having amino acid oxyproline in its structure. Results adjuvant into posterior right leg of animal [8]. Indometa-of studying the latter in biologic fluids adequately reflect cin induced gastro- and nephropathies were produced by process of collagen formation [1, 2]. Therefore studying administration of indometacin per os as water suspension structure of this amino acid in tissues it may be prede- at a dose 2.5 mg/kg during 5 days [9]. All painful pro-termined a state of collagen formation and regeneration cedures were performed in accordance with the WMA processes of ulcerous-erosive disorders in mucosa of gas- Declaration of Helsinki. To perform biochemical studies trointestinal tract (GIT). As regards renal tissue a content all the animals were single-stage decapitated under ether-of oxyproline specifies a state of inflammation process ac- ization. Stomach was extracted, then purified, washed companying by sclerosis of renal tissue [3, 4, 5, 6, 7]. with a cold physiological solution, proventriculus was
Aim of research was to study a state of collagen removed. Mucous layer then was scarified, weighed and synthesis in gastric mucosa and renal tissue in indo- slurried in distilled water at a rate 30 mg/ml. metacin gastropathy in animals with experimental Kidneys were crushed and homogenized in a glass
rheumatoid arthritis. homogenizer with Teflon pestle in 3-4-fold volume
Materials and methods of research: Experimental of excretion medium consisting of 0.25M saccharose, studies were carried out on 21 male rats of mixed popula- 0.05M KCl in 0,05M solution tris HCl buffer (pH 7.4). tion with mass 160-200 g that were on common ration of To precipitate nuclei, mitochondria and disordered cells vivarium. Animals were divided into 3 groups of 7 animals homogenates were centrifuged in 9000 g during 20 mineach. The 1st group was intact, the 2nd group with experi- utes. Content of oxyproline in supernatant fraction of mental rheumatoid arthritis (ERA), the 3rd group - ani- homogenate was determined by a method of A. Steven mals with ERA and indometacin gastropathy (GERA). and co-authors [10].
STATE OF COLLAGEN SYNTHESIS IN GASTRIC MUCOSA AND RENAL TISSUE IN INDOMETACIN GASTROPATHY...
Results obtained were treated with using of Student's Results and their discussion: Results of studying a
t-criterion by a statistically standard package of Micro- content of oxyproline in gastric and renal tissue are given soft Excel. Differences considered valuable in p < 0.05. in the table.
Table 1. - Content of oxyproline in gastric mucosa and renal tissue in indometacin gastropathy in animals with experimental rheumatoid arthritis
Group of animals Oxyproline. nmol/mg P
Stomach kidneys
Control 2.12 ± 0.077 5.28 ± 0.180 < 0.001
ERA 1.95 ± 0.062 7.16 ± 0.315 < 0.001
GERA 0.44 ± 0.019 14.51 ± 0.384 < 0.001
Note: p - reliability from indices of control group.
How it is seen from the presented data a content of oxyproline in gastric mucosa in ERA is practically not differed from control group, whereas it is reliably increased 35.6% from index of control group. Reduction in content of oxyproline noted to be in gastric mucosa 79.3% from control group in using of indometacin (GERA). Content of oxyproline in renal tissue was increasing 174.8% in this group. Probably, suppression of regeneration processes by indometacin in gastric mucosa was caused by abnormalities in functioning of numerous inter-caused cytoprotec-tive factors that leads to lowering ofpost-epithelial factors of protection, which principal element are «cytoprotec-tive» prostaglandins. It is established that prostaglandin E2 implements its protective potential on suppression of formation ofgastric acid, increase of mucus and bicarbonate secretion, stimulation of regeneration.
Unlike to stomach a considerable increase of oxyproline in application of indometacin observed to be in kidneys. It is likely to be caused by some inter-related mechanisms. Block of synthesis of renal prostaglandins by indometacin increases and prolongs vasoconstrictive action of angiotensin II playing a key role in progressive lowering of renal function by means of hemodynamic
and «non hemodynamic» mechanisms [11, 12]. Renin-angiotensin-aldosteron system actuates when release of renin by juxtaglomerular cells ofkidneys occurs. The latter catalyzes transformation ofangiotensin in angiotensin I in the liver. Then locally in tissues occurs transformation of angiotensin I in angiotensin II (active form) - under participation of angiotensin I converting enzyme. Production and release of aldosteron, proximal canalicular re-absorption of sodium, shortening of afferent and efferent arteri-oles, heightened saline appetite, inhibition of parasympa-thetic nervous system, stimulation of j8-adrenoreceptors, intensification of proteinuria - it is not complete list of effects provoked by angiotensin II. Mechanisms considered prove involvement of both glomerular and tubular-interstitial apparatus in damage of kidneys by indometacin.
Conclusions:
1. Indometacin considerably reduces a content of oxyproline in gastric mucosa that confirmed suppression of regeneration processes.
2. Preparation increases a content of oxyproline in renal tissues in indometacin gastropathy that exhibited appearance of inflammation process leading to renal tissue sclerosis.
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