Ganchev, T.

Ilkova, R.

Negrev, N.

English

Varna Medical University Press: Journals

I N F L U E N C E O F C O L C H I C I N E O N T H R O M B O C Y T O P O I E S I S A N D P L A S M A T H R O M B O C Y T O P O I Е Т I N A C T I V I T Y I N R A T S T. Ganchev, N. Negrev. R. Ilkova Key-words: colchicine — thrombocytopoiesis - bone marrow megakaryocytes — plasma thrombocytopoietin. I t is known that colchicine treatment induces specific complexing together wi th tubulin cel lular molecules (3) which Inhibits their assembling into micro­tubules (MT) (7). T h i s exerts a negative effect on mitotic processes and functions of numerous cel lular systems 4 (4, 7) . Treatment wi th colchicine in strong dose s results in leukocytosis, thrombocytosis and bone-marrow applas ia when blood system is concerned (7). Concerning thrombocytes themselves* colchicine i n M T destructing doses inhibits s l ight ly the retraction of f ibrin coagulate and the l iberat ion of serotonin as well as the aggregation of t h r o m b o c y t e s (12, 14). Recent ly , Handagama et a l . (9) have observed thrompbocytopoiesis in­hibit ion after microtubule destruction by colchicine. There are no data in the literature avai lable about the influence of t h e changes determined by colchicine on plasm-i Hir>m ')o^ytopУЫ\П ( T P ) ac t i ­v i ty . T h i s fact as well as the c o n t r o v e r s i e s j> ' ^ i • i o n : datft ci ted insisted us to study thrombocytopoiesis* bone-marrow megakaryocytes ( M K C ) and plasma T P ac t iv i ty after 3-day low-dose colchicine treatment in r a t s . M a t e r i a l a n d methods Bll Our observation was carried out on 69 white male rats of Wis ta r breed w i t h body weight of 190—200 g and 20 white male recipient mice wi th body weight of 25—30 g. Animals were divided into an experimental and a control group. Exper imen ta l rats wen treated w i t h colchicine at dosis of 0.5 mg/kg b. w. da i ­ly intraperi toneally for 3 days but the control animals were administered a physiological sal ine. Thrombocyte count was estimated after L i s i c h k o v ' s pha­sic-contrast method (9) . 75-Selenomethionine ( 7 5 Se-M) incorporation into new­ly-formed thrombocytes ( i . e. the most significant index of the state of thrombo-cytopoiesis) as wel l as plashia T P ac t iv i ty was assessed after Penington's method in our own modification (Negrev and Ganchev, 15). Bone-marrow megakaryo-cytogram was estimated after the method of Lev ine et a l . (10) . The data were processed by the method of var ia t ion analysis . Resu l t s a n d discuss ion Our data obtained are presented on fig. 1 and 2 and on table 1. On fig. 1-a one can see that 3-day colchicine treatment reduces signif icantly thrombocyte coun t i n comparison wi th that of the control animals . 7 5 S e - M incorporation 46 Т. Ganchev, N . Negrev, R . Ilkova into newly-formed thrombocytes is significantly inhibited, too (fig. 1-b). Bone-marrow M K C analysis reVeals their diminution not only as a to ta l number but also as number in the single stages of their development ( I s t , I I r J , I I I " 1 , and especially I V t h stage). P lasma T P ac t iv i ty tested on 20 recipient mice by means of two parameters (thrombocyte count and percentage of incorporated 7 5 Sa-M) under the ihfluence of assessed plasma from animals treated w i t h col­chicine, on the ofte hand, and wi th saline, oft thfc other hand, is s ta t i s t i ca l ly ! significantly higher in eolchicine-treated animals ' plasma than in the contro one (f ig. 2-a, b). An additional study by using 8- and x-lumicolchicine in 27 male rats does not show any significant differences in thrombocyte count and especially in the percentage of incorporated 7 5 Se-M in comparison wi th that of saline-tre­ated controls. Th i s enables saline application as a reliable control when expe­riments wi th colchicine in this system are concerned. Our data abou hrombocyte count reduction are in concordance w i t h those of other authors (9) and contrary to Dustin 's results (7). The considerable throrn­bocytopoiesis inhibition after colchicine treatment indicated main ly by means of reduced thrombocyte count, percentage of 7 5 S e - M incorporated into newly-formed thrombocytes as wel l as of general megakaryocytopoiesis suppression proves that both dosis and time duration of the experiment selected b y us are inhibitory effective concerning thrornbocytopoiesis. I t stresses t h M M K C count decreases significantly ill general and in the single stages, especially in the fourth one (by 57.14 per cent). A H differences were statist ically rel iably at p < 0 . ( ) 0 1 . I t is known that during the last stage of mi\gakaryo:ytopoiesis the greatest number of M K C are liberated followed by the other stages (5) . I t is probably the main reason for peripheral thrombocyte count reduction and for diminut ion of the percentage of 7 5 Se-M incorporated in thrombocytes! when colchicine-tre­ated rats are concerned. In regard to the increased plasma T P ac t iv i ty ( T P is considered a basic specific thrornbocytopoiesis regu la to r—11) after colchicine treatment establi­shed in our study it has to be noted that the missing l i terature data do not allow us to perform a comparative analysis. I t is considered proved that negative feed­back mechanises participate at T P biogenesis (2) . The reduction of thrombocyte count and of the percentage of 7 5 Se-M incorporated into newly-formed thrombo­cytes as wel l as of M K C number in a l l stages (and especial ly in the th i rd and fourth one) are most probably those factors in feed-back mechanisms which in­duce T P biogenesis increase in our study. In our opinion, M T destruction after colchicine treatment results probably in supperssion of proliferation as wel l as in inhibi t ion of M K C differentiation. Thus it does not influence directly negat ively upon structures responsible for T P biogenesis. M K C count reduction, especially in the first stage, can be due additionally to an inhibited transition of immediate M K C precursors to this cel lular fund that is again a concequence of anti tubular colchicine effect. I t is possible that after colchicine treatment other well-known inhib i tory and side effects of colchicine participate at the inhibit ion of bone-marrow mega­karyocytopoiesis and thrornbocytopoiesis, respectively (6, 8, 13). We can conclude that our data prove the negative influence of M T destruc­tion after colchicine treatment on megakaryocytopoiesis and thrornbocytopoi­esis. However, colchicine treatment does not restrict plasma T P biogenesis but induces by means of suppressed megakaryocytopoiesis and thrornbocytopoie­sis , respectively, its significant increase. Influence, f colchicine o n . : 47 %753e-M oo zoo 100 238,43+26,48 10,38*0,51 Ш 221,56 ±16,26 i i I 5,54*0,23 ФА • 4 i i Colchicine Saline Colchicine Saline -1.2 10 в 6 4 2 0 g. 1. Thrombocyte number and percentage of incorporated "Selenomethionine ( 7 5 St- M) newly-formed thrombocytes after colchicine treatment in rats. Л-thrombocytes Colchicine — n = 16 P S — n - 10 В — percentage of incorporated 7 5 Se-M Colchicine — n = 8 P S — ii - 8 Data are presented as x — S x . UoVi 800-600 -400 -200 0 713*38,54 5,32*0,38 A Colchicine £5=? 452*44,70 I о4» CO 2,33*0,06 Valine Co i Б nicine i -3e~ft> 6 5 4 3 Fi£. 2. Plasma .thrombocytopoietin activity estimated by the changes of thrombocyte number-and of percentage of incorporated 7 5 Se-M in newly-formed thrombocytes of recipient mice. A — thrombocytes Colchicine — treated with plasma from colchicine-injected rats; n = 8. P S — treated with control plasma; n = 8. В — percentage of incorporated 7 5 Se-M. Colchicine — treated with plasma from colchicine-injected rats: n — 10. P S — treated with control plasma; n = 10. R E F E R E N C E S 1. Л и с и ч к о в, Т. В . В: Нарушения на хемостазата. София, Медицина и физ­култура, 1987, 46—90. — 2. С с л и в а н о в, В . А., В . Г. Т я ж е л о в а. Цитология, 1984. Ко. 2, 224—228. — 3. С a s I 1 е, A . G . , N . С г a f w о г d. Thrombos. Haemostas., 39, 1978, 386—403. - 4. C h a l d a k o v , G . N . . V . N . V a n k o v . Atherosclerosis, 61, 1986, 175—192. — 5. С h е г n о f f, A . , R. F . L c v i n c , W. S. G o o d m a n . J. Clin. Invest, 65, 1980, 926—930. — 6. D е С h a t с 1 е t, С. R., M. R. C o o p e r , С. E . M c C a l l . Infect. Imtnun., 3, 1971. 66—72. — 7. D u s t i n, P . In : Microtubules. New York , Springer-Verlag, 1978, 167—225. — 8. F l o w e r , R. J . , S. M o n c a d a, J . R, V a n e . In: The Pharmacological Basis of Therapeutics. A . G i 1 m a n, A. G o o d-rn a n and A. G i 1 m a n, eds. New York, MacMillan Publ . Corp., 1980, 718—720. — 9.. H a n d a g a m a. P . P . J . , B . F . F е 1 d m a n, N . C . J a i n, Т. B . F a r v e r , C . S. К о n o . Amer. J. Veten Res., 48, J987, 1142—1146. — 10. L e v i n e, R, F . , К. C . H a z z a r d , J . D . L a m b e r g. Blood, 60, 1982, 1122—1131. — 11. M c D o n a l d , Т. P . , M. C o t t e r е I , R. С l i f t , J . А. К h o u r i , M . D. L o n g . J. Labor. Clin, Med., 106, 1985, 162—174. — 12. M е n с h c, D. , A . I s r a e l , S. К a r p a 1 k i n. J. Clin. Invest., 66, 1980. 284—291. — 13. M i z с 1 1, S. В . , X. W i l s o n . Biochemistry, 11. 1972. 2573—2578. — 14. M o a k e, J . L . , P . L . С i m о, K . W i d m e r , D . M . P e t e r s о n, J . R . G u m. Thrombos. Hae'mosias., 38, (977, 420—428. — 15. N е g r е v • | . J . G a n c h e v . Acta Physiol. Pharmacol. Butg., 13, 1987, 35—40. ВЛИЯНИЕ КОЛХИЦИНА НА ТРЭМБОЦИТОПОЭЗ И ТРОМБОЦИТОПОЭТИНОВ УЮ АКТИВНОСТЬ ПЛАЗМЫ У КРЫС 7. / анчса, //. Нсгрее, Р. Илкова ИГЗ Ю М Е Изу'иет. 'ч злн?'>ие ко шгцнча как аитнтубулирнын агент на показатели тромбоцито-поэзз и тромбоцитопоэтинозую активность плазмы у крыс. Колхицин применялся в дозе 0,5 мг 'кг телесного веса в день, в течение трех дней. Устанавливается, что колхицин статистически значимо уменьшает число тромбоцитов, процент включенного 7 5 ссленометионина в новообразовавшихся тромбоцитах н клетках мегакарио штиного ряда, в особенности в их зрелых формах. Плазменная тромбоцитопоэти-новая активность, которая определялась на мышах-реципиентах посредством изменения числа тромбоцитов и процента включенного 7 5 селенметионина, показывает сильное увели> чение у крыс, которым вводился колхицин. Авторы полагают, что мнкротубулярная деструкция после введения колхйципа,инги бнруя мегакарноцитопоэз и тромбоцнтопоэз у крыс, наверное, по принципу обратной связи, стимулирует биогенез тромбоцнтопоэтниа — специфического гуморального регулятора тромбоцигопоэза. Делается заключение, что мнкротубулярная деструкция не оказывает отрицательного воздействия на структуры и механизмы, ответственные за тромбоцитопозтиноеын бпогензе при указанной дозе и дтнге:{ыо:гн в з е х м м к з . т - м д п з в и а ц я я о .шге . ШШЬ ' I I I I.' '! ' !•; :l 

INFLUENCE OF COLCHICINE ON THROMBOCYTOPOIESIS AND PLASMA THROMBOCYTOPOIÐ•Ð¢IN ACTIVITY IN RATS

https://journals.mu-varna.bg/index.php/ssm/article/download/3749/3231

INFLUENCE OF COLCHICINE ON THROMBOCYTOPOIESIS AND PLASMA THROMBOCYTOPOIÐ•Ð¢IN ACTIVITY IN RATS

Abstract

Similar works

Full text

Available Versions

Varna Medical University Press: Journals