Uticaj produžene peroralne primene eugenola na hematološke i neke biohemijske parametre krvi kod pacova

Abstract

Ispitivano je moguće hematotoksično, hepatotoksično i nefrotoksičano dejstvo eugenola kod pacova posle dvonedeljne i četvoronedeljne kontinuirane p.o. primene. Ogled je izveden na 72 mužjaka pacova soja Wistar podeljenih u šest grupa. Četiri grupe tretirane su različitim dozama eugenola (10 mg/kg tm/dan, 50 mg/kg tm/dan, 200 mg/kg tm/dan i 400 mg/kg tm/dan). Peta, kontrolna grupa dobijala je vehikulum (0,5% metil-celuloza, 20% propilen-glikol i voda), a šesta je bila apsolutna, netretirana kontrola. Eugenol i vehikulum aplikovani su gastričnom sondom, svakodnevno tokom četiri nedelje u količini od 1 ml/100 g telesne mase pacova. Krv je uzorkovana kardijalnom punkcijom anestetisanih pacova 14. i 28. dana ogleda u cilju određivanja hematoloških i biohemijskih parametara krvi: hematokrit, broj eritrocita, leukocita i trombocita, leukocitna formula, koncentracija hemoglobina, MCV, MCH, koncentracija proteina, albumina, uree, kreatinina, kao i aktivnost alanin-aminotransferaze (ALT), alkalne fosfataze (ALP) i kreatin-kinaze (CK). Rezultati su pokazali da eugenol primenjivan tokom dve i četiri nedelje u dozama od 10, 50, 200 i 400 mg/kg tm/dan ne ispoljava hematotoksično, hepatotoksično niti nefrotoksično dejstvo. Eugenol davan tokom četiri nedelje ne utiče značajno na broj eritrocita, koncentraciju hemoglobina, hematokrit, zapreminu eritrocita, broj leukocita i leukocitnu formulu. Primenjivan tokom dve nedelje, prouzrokuje značajno povećanje mase hemoglobina po eritrocitu. Ovaj efekat je nespecifičan i ne zavisi niti doze, niti od dužine tretmana. Doze eugenola od 10 i 200 mg/kg/dan primenjivane tokom četiri nedelje prouzrokuju značajno smanjenje broja trombocita, dok najviša ispitivana doza (400 mg/kg/dan) prouzrokuje značajno povećanje, u poređenju sa brojem trombocita kod pacova tretiranih dozom od 10 i 200 mg/kg/dan. Promene broja trombocita izazvane eugenolom kvalitativno su različite i ne zavise od doze, niti od dužine tretmana. Eugenol primenjivan tokom dve i četiri nedelje ne utiče značajno na proteinemiju, albuminemiju, koncentraciju uree i kreatinina, kao i aktivnost ALP u serumu pacova. Tri ispitivane doze eugenola (10, 50 i 200 mg/kg/dan) značajno smanjuju, dok najviša doza povećava aktivnost ALT. Eugenol aplikovan tokom četiri nedelje u dozi od 200 i 400 mg/kg prouzrokuje statistički značajno smanjenje aktivnosti CK.

The possible haematotoxic, hepatotoxic and nephrotoxic effects of eugenol in rats after two-week and the four-week continuous use were tested. The experiment was conducted on 72 male Wistar rats divided into six equal groups. Four were treated with different doses of eugenol (10 mg/kg bw/day, 50 mg/kg/d, 200 mg/kg bw/d and 400 mg/kg bw/d), the control group received the vehikulum (0.5% methyl cellulose, 20% propylene glycol and water), and the sixth group was the absolute, untreated control. Eugenol and the vehikulum were administered with a gastric probe, on a daily basis, for four weeks at a rate of 1 ml/100 g body weight of rats. Blood was collected by cardiac puncture of the anesthetised rats on days 14 and 28 in order to assess the haematological and biochemical blood parameters: haematocrit, red blood cell count, white blood cell and platelet counts, leukocyte formula, hemoglobin, MCV, MCH, total protein concentration, albumin, urea, creatinine, and the activity of the alanine aminotransferase (ALT), alkaline phosphatase (ALP) and creatine kinase (CK). The results showed that, having been applied for two and four weeks at doses of 10, 50, 200 and 400 mg/kg bw/day, eugenol did not show any haematotoxic, hepatotoxic or nephrotoxic effects. Eugenol administered for four weeks does not significantly affect the number of erythrocytes, haemoglobin concentration, haematocrit, red blood cell volume, leukocyte count and leukocyte formula. Applied for two weeks it caused a significant increase in the mass of haemoglobin in erythrocytes. This effect is not specific and does not depend on the dose or the treatment duration. Eugenol in doses of 10 and 200 mg/kg/day applied for four weeks caused a significant reduction in the number of platelets, whilst the highest dose tested (400 mg/kg/day) caused a significant increase in comparison to the number of platelets in rats treated with 10 and 200 mg/kg/day. Changes in the number of platelets induced by eugenol qualitatively different and are not related to dose or length of treatment. Eugenol applied for two and four weeks does not significantly affect proteinaemia, albuminaemia, serum urea and creatinine concentrations, and serum ALP activity in rats. Three assessed doses of eugenol (10, 50 and 200 mg/kg/d) significantly decreased, whereas the highest dose increased the ALT activity. However, eugenol applied for four weeks at a dose of 200 and 400 mg/kg/d caused a statistically significant decrease in CK activity.