Softova, E.

Zlateva, M.

English

Varna Medical University Press: Journals

PROGRESS OF T H E R E G E N E R A T I V E PROCESSES I N A R T I F I C I A L S K I N WOUNDS AGAINST T H E BACKGROUND OF A PRELIMINARY CHRONICAL INTOXICATION WITH PHOSPHOR-ORGANIC P E S T I C I D E "ZOLON" E. Softova, M. Zlateva The postraumatic regeneration of the skin is a complex process and its course (progress) can be accelerated or delayed under the influence of varius factors of the organism itself and the environment. I n the available literature there are many data of s t imulat ive or depressive effect on the progress of the skin regenerative processes. For example: Some hormones (5,20), ascor-binic acid (18), medicines — (1,19) etc. influence on the processes. On the other hand, very scarce facts can be found about the effect of the production-environment (4, 16). The investigation of the posttraumatic skin regeneration of agricultural workers arouse certain interest: they contact constantly some chemicals and their work itself suggests more often wounds and injuries. I t is a l -ready known that pesticides have a depressive effect on the immunological reactions ( 1 , 13, 21), also that after certain disorders, of the immune mecha-nisms, the regulation of the regenerative processes is disturbed (3, 15). Presuming a l l that, we have for an object of the present study to fol-low the regenerative skin processes after a prel iminary intoxication wi th phosphororganic pesticide "Zolon" ( P P Z ) applied as a plant-protector in agriculture. Material and methods The study covers 63 white male rats wi th in i t i a l weight of 120—140 gm, which were given P P Z per os (doses 1 / 1 0 0 and V̂ oo L D 5 0 ) in an aqueous solu-tion for 5 months every day. The animals were divided in groups of 7. 21 of them were control. After the 5 t h month subcutaneous tissue wounds were performed under an ether narcosis. The dimentions of the wounds were 2/2 cm. Each 7 t h , 14 t h and 3 0 t h day a histological material was taken, fixed in formaline and Carnua-solution. The paraffin cuts (sections) were stained wi th hemalaun-eosin after the method of van Gieson for the connective tis-sue. PAS-react ion of Mc Mannus was done to detect the glycogen and B r a -cheau-reaction to establish R N A . Results and discussion W e analyse both doses and their effect on the regeneration of the wounds, because the results of our histological study show a degree difference only, concerning the way and time of the processes. Progress of the regenerative processes in artificial. 85 Seventh Day: Both groups of animals perform their wound-regenera-tion under the crust. The surface wound layer is abundant in leucocytes, forming abscesses here and there (fig. 1). I n comparison with the controls, it i s obvious that many leucocytes can be found deeply amidst the granula-tive tissue of the experimental animals . Proliferation of endothelial and Fig . 1: Abscesses in the superficial vulneral layer of animals treated with 1/100 L D 5 ( > P P Z (7th day). H . E . , M x 10x10 adventit ic cells is established in "de novo" formed vessels, The granulative tissue of the animals treated with P P Z is loose, swelled, wi th scarce number of fibroblasts. The cytoplasma of the latter has less glycogen and R N A than that of the controls. The new-formed collagen fibres in the subwound layer are irregularly dispersed and can hardly be stained. The blood vessels in these regions are dilatated and their wa l l s are soaked wi th P A S ( + ) non-glycogenic substances. Some wounds of the animals do not produce a granu-lat ive tissue, but a heavy swell and leucocyte infi l trat ion is established. The animals treated wi th 1 / 5 0 0 L D 5 0 P P Z have plasmatic cells together wi th the grouped leucocytes. The crawling epithelium over the wound is 3 times thicker than normally and the glycogen of the new-formed epithelial cells is irregularly scattered. RNA-quant i ty is very low. The wound-surrounding tissue of a l l groups experimental animals is edematic wi th excess of lympho-cytes, plasmocytes, leucocytes and mastocytes; the lymphoid form prevails . Fourteenth Day: Greater number of experimental animals have their wounds covered with detritic materia (not epithelium) with many leucocy-tes, while the controls show almost final regenerative processes. The granu-la t ive tissue is s t i l l abundantly irrigated, some blood vessels are dilatated and their wal ls are soaked wi th P A S ( + ) nonglycogenic materia. Increased Е. Softova, М. Zlateva quantity of lymphocytes, plasmocytes with pirinofil ic cytoplasma and ma-stocytes is established when compared to the controls. The fibroblasts and fibrocytes are less in number and scarce amount of glycogen and R.N A can be detected in their cytoplasma.Near the wound edges new-formed collagenic fibres are found, but greater number of them possess poor tinctorial proper-Fig . 2: Thin and infiltrated with leucocytes "crawling" epithelium (14th day). H.E.> М . х Ю х б . З » ties. Some of them are quite wrinkled, whi r ly dispersed, with various thick­ness. Heaps of P A S ( + ) structureless materia can be seen amidst the granu-lat ive tissue. The surrounding tissue is edematic and possesses round cells main ly . The crawling epithelium over the wound has only 2—3 rows of cells, somewhere is stratificated or infiltrated with leucocytes (fig. 2) . I t forms deep inserts in the sublocated tissue of some animals. Glycogen can be found only in definite epithelial cells and RNA-quant i ty does not differ from that of the former group. A cuneiform cicatrice with disorientated collagenic fibres and lymphocytic deep infil tration is established in some of the ani­mals treated with V 5 0 0 L D 5 0 P P Z . Thirthieth Day: Complete epithelization of the wound surface is found in 2/-6 of the experimental animals, whi le only one of the controls has an in­complete epithelization. The maturation of the granulative tissue is delayed and unnormal, fields of homogenous cicatrices and hyal inizat ion can be seen. The collagenic fibres are unproperly orientated in greater number of cases. Some of them are rough and ondulated. Plasmat ic cells, lymphocytes and mastocytes with a lymphoid form can be found amidst the granulative tissue. Leucocyte forming microabscesses are established in the collagenic tissue of some animals. No glycogen is found in the fibroblastotic cyplasma, Progress of the regenerative processes in artificial. 87 but there is certain amount of R N A . Here and there the tissue is edematic and soaked with P A S ( + ) nonglycogenic substance. The quantity of R N A and glycogen is reduced i n the cell-cytoplasma of the covering epithelium. The changes in the animals treated wi th V 5 0 0 L D , ^ P P Z are slighter expres-sed and do not differ considerably from the controls. Based on the study, it is obvious that animals subjected to a conti-nuous treatment wi th P P Z could regenerate their sk in wounds quite diffe-rently concerning the morphological reaction and the terms of production and maturation of the granulative tissue, as wel l as their epithelization. T h i s i s manifested wi th a suppression of the mesenchymic cell reaction. I t is important that there is an excess of leucocytes in the early and later periods, not only in the wound (vulnus) layer, but also in deeper regions. Garshin V . G . (1) suggests that it is an index of the pathological state of the granulative tissue. Besides, the wounds of the control-group animals acquire (since the first days) many fibroblasts wi th abundant glycogen in their cytoplasma. I n comparison with them the wounds of the experimental animals have a slight quantity of this substance, which is extremely impor-tant for the regenerative processes (12, 17). To support this fact (wound regeneration — in the way of insufficient granulative tissue) comes the de-creased quantity of R N A in the cell elements. Usua l ly , when the wounds recover normally, the RNA-amount in the granulative-tissue cells reaches its maximum about the 8 t h — 10 t h day (22), while our investigation of the animals shows that its quantity is s t i l l small on the 14 t h day and approa-ches the control level on the 3 0 t h day. Together with the pathology of the granulative tissue, the experimental animals present a suppression of the collagen-production. I t is supported by the presence of N M P S in subvulneral tissue unt i l the 30 t h day , presuming-that they are necessary to form the collagenic fibres in the early terms of the wound-regeneration (9). The epithelization is also delayed and the craw-l ing epithelium is out of order, thin and infiltrated wi th leucocytes. Some-thing more: the presence of numerous leucocytes and plasmocytes in the gra-nulat ive tissue of almost every experimental animal confirms the tension of the cell immuni ty ( 1 , 14). The precise mechanism can hardly be explained: the suppression of the wound-regeneration of animals treated wi th P P Z is unclear. I t could be suggested that the active toxic substance tends to a decreased tissue (cell) metabolism, which is a condition of a suppression of the elements of the macrophagial system (10) and regeneration-inhibition. The experiments of Homullo G . V . et a l . (11) also prove that the chronic hypoxia tends to an inhibit ion of the fibrillogenesis and a delay of the regenerative processes. On the other hand the pesticides' action can be direct too: by disorders of the metabolism and a suppression of the oxy-reductive processes (6, 7, 8 ) , resulting in the cell breathing. Undoubtful role play the disorders of the vascular permeability, developed under the influence of the pesticides. I n conclusion, it can be suggested that though slight toxic, the P P Z tends to abnormal course (progress) of the regenerative processes of the wounds. I t must be contributed to the hygienic indexes for the workers dealing with this substance. 88 Е. Softova, М. Zlateva R E F E R E N C E S 1. А н и ч к о в , И. Н . , К- Г. В о л к о в а , В. Г. Г а р ш и н. — В: Мор­фология заживления ран. М., Медгиз, 1951. — 2. А р и п д ж а н о в, Г. М. Гиг. и санит., 1973, № 7, 39. — 3. Б а б а е в а , А. Г. В: Иммуннологические механизмы регуляции восстановительных процессов. М., Медицина, 1972. — 4. В о й т к е -в и ч, А. А. и д р . Бюлл . эксперим. биол. и мед., 1959, № 2, 47. — 5. В о й т к е -в и ч , А. А. Д о к л . АМН СССР, 1957, 115, № 3, с. 630. — 6. О р л о в а , Н . , Л . А. Х о в а е в а , М. Я. А к и н ч е в а . Вопр. питания, 1971, № 6, 32. — 7. Р а п ­п о п о р т , М., Б . , Л . А. М а т о х н ю к. Врач, дело, 1971, № 8, 132. — 8. С а ­п е г и н, Д . И. и д р . Гиг. и санит., 1976, № 11, с. 97. — 9. Ф у к с , Б . Б . В: Очерки по проблеме регенерации. М., 1966, с. 56. — 10. X о м у л л о, Г. В. В: Ре-гуляторные механизмы регенерации. М., 1973, с. 29. — 11. X о м у л л о, Г. В. и др . Косм. биол. и мед., 1976, № 2, 68. — 12. Ш а м р а й, П. Ф. В: Морфология процессов адаптации клеток и тканей. М., 1971, с. 44. — 13. D е s i , I . , L . V a r g a, I . F a r k a s. Ж- гиг., эпидемиол. и микробиол., 22, 1978, № 1, 102. — 14. F i с h -t е 1 i u s, K . F . Acta pathol. et microbiol. Scand., 1962, № 11, p. 52. — 15. G u -z е k, J . W . Nature, 201, 1964, № 4922, p. 930. — 16. H a n d m a n, W. — цит. no И. К. Е с и п о в а. В: Очерки по проблеме регенерации. М., 1966, с. 17. — 17. Н о о-p e s , J . Е. , J . С. M i c h a e l . J . Surg. Onkol., 6, 1974, № 5, 409. — 18. J o r -d е n s е n, O. Acta pathol. et microbiol. Scand., 60, 1964, № 3, p. 365. — 19. M a y, R . M. Acad. Sc i . , 247, 1958, № 19, p. 1670. — 20. M o l t k e , E . Acta endocrinol., 29, 1958, № 3, p. 421. — 21 . P i p y , В . , D. G a i 1 1 a r d, R . D е г а с h e. Med. et chir. dig., 6, 1977, № 7, 473. — 22. W i l l a m s o n , M. B . Proc. Soc. Experim. B i o l . , 136, 1971, 1336. ПРОТЕКАНИЕ РЕГЕНЕРАТОРНЫХ ПРОЦЕССОВ В ИСКУССТВЕННО ВЫЗВАННЫХ КОЖНЫХ РАНАХ НА ФОНЕ ПРЕДВАРИТЕЛЬНОЙ ХРОНИЧЕСКОЙ ИНТОКСИКАЦИИ ФОСФОРОРГАНИЧЕСКИМ ПЕСТИЦИДОМ »ЗОЛОН» Е. Софтова, М. Златева Р Е З Ю М Е Проведено исследование 63 белых мужских крыс, которые затраЕЛЯЛись в тече­ние 5 месяцев фосфорорганическим пестицидом «золон» в дозах 1/1С0 Л Д 5 0 и 1/5С0ЛД 5 0, после чего на спине у животных наносились послойные кожные раны размерами в 2/3 см. Заживление ран прослеживалось на седьмой, четырнадцатый и тридцатый день. Устанавливается сравнительнсе замедление регенераторных процессов у живот­ных, которые подвергались действию «золона». Заживление у них отличается от за­живления у контролей как созреванием грануляционной ткани, така и ее эпителиза-цией. Наблюдаются преобладание лейкоцитов в поверхностных и глубоких слоях, подавление мезенхимной клеточной реакции в грануляционной ткани, наличие не­большого количества Р Н К и гликогена в фкбрсбластах. Образующийся над раневой поверхностью эпителий Я Е Л Я С Т С Я расслоенным, истонченным и инфильтрированным лейкоцитами. Наблюдаемое замедление регенераторных процессов при заживлении кожных ран объясняется эвентуальной тканеЕОЙ гипоксией, развиЕакщейся при хронической интоксикации с подавлением пролиферации элементов макрсфагглгной системы и нарушением процессов заживления , с одной стороны, а с другой — непосредственным токсическим действием пестицида «зелен», приводящим к нарушению метаболитного обмена и клеточного дыхания. 

PROGRESS OF THE REGENERATIVE PROCESSES IN ARTIFICIAL SKIN WOUNDS AGAINST THE BACKGROUND OF A PRELIMINARY CHRONICAL INTOXICATION WITH PHOSPHOR-ORGANIC PESTICIDE "ZOLON"

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PROGRESS OF THE REGENERATIVE PROCESSES IN ARTIFICIAL SKIN WOUNDS AGAINST THE BACKGROUND OF A PRELIMINARY CHRONICAL INTOXICATION WITH PHOSPHOR-ORGANIC PESTICIDE "ZOLON"

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