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The present study was carried out to evaluate the effect of piperine pre-conditioning on the pharmacokinetics of marbofloxacin in Wistar rats. Marbofloxacin was administrated at a dose rate of 5 mg/kg body weight alone, and along with piperine pre-conditioning at a dose of 10 mg/kg of body weight, orally for 5 days in Wistar rats. The mean values of the half-life (t1⁄2β), maximum drug concentration (Cmax) and area under the curve (AUC) were 1.19 ± 0.17 h, 2.71 ± 0.09 μg/mL and 12.25 ± 0.77 μg.h/mL, respectively, in piperine pretreated rats. The values were significantly higher than the values observed in rats administered with marbofloxacin alone (1.12 ± 0.31 h, 2.28 ± 0.20 μg/mL and 9.24 ± 0.59 μg.h/mL, respectively). The drug clearance (ClB) in piperine pretreated rats was 0.04 ± 0.02 L/h/kg, which was significantly lower than the clearance rate of the drug (0.53 ± 0.03 L/h/kg) in the animals administered with marbofloxacin alone. The study reveals that piperine has a significant effect on the pharmacokinetics of marbofloxacin, which may be due to an increase in the drug absorption and inhibition of elimination of the drug in rats., U ovom je radu istražen učinak pretkondicioniranja piperinom na farmakokinetiku marbofloksacina Wistar štakora. Marbofloksacin je apliciran u dozi od 5 mg/kg tjelesne mase peroralno, samostalno i nakon pretkondicioniranja piperinom u dozi od 10 mg/kg tjelesne mase peroralno tijekom 5 dana. U štakora tretiranih piperinom prosječne vrijednosti poluživota (t1⁄2β) bile su 1,19 ± 0,17 h, maksimalna koncentracija lijeka (Cmax) 2,71 ± 0,09 μg/mL, a površina ispod krivulje (AUC) 12,25 ± 0,77 μg.h/mL. Navedene vrijednosti bile su znakovito više od onih utvrđenih u štakora tretiranih samo marbofloksacin (1,12 ± 0,31 h, 2,28 ± 0,20 μg/mL i 9,24 ± 0,59 μg.h/mL). Klirens lijeka (ClB) u štakora tretiranih piperinom bio je 0,04 ± 0,02 L/h/kg što je bilo znakovito niže od klirensa lijeka (0,53 ± 0,03 L/h/ kg) u životinja koje su dobivale samo marbofloksacin. Ovo istraživanje pokazuje da piperin znakovito utječe na farmakokinetiku marbofloksacina, što može biti posljedica povećane apsorpcije lijeka i inhibicije uklanjanja lijeka u štakora.

This study was an attempt to determine biomarkers of non-ionizing, low-level microwave exposure in an animal model. It investigated the effects of continuous-wave radiation on peripheral blood in Wistar rats. The radiation frequency applied was 2450 MHz, while the average power density of the induced field was 10 mW/cm2. Forty 13-week-old male Wistar rats with an average body mass of 350 g were divided into groups G1 and G2. Group G2 comprised 20 animals, exposed to microwaves for 30 days (5 days a week, 2 hours a day), and group G1 comprised 20 unexposed controls. Peripheral blood samples were taken immediately after irradiation on the 1st, 8th, 16th and 30th day of the experiment. The total number of erythrocytes and leukocytes as well as the differential leukocyte count were investigated and compared. The results revealed an insignificant increase in the total erythrocytes count in microwave-exposed animals (P>0.05) in comparison to controls. Total leukocyte count was consistently decreased in irradiated animals from eight day of irradiation (P0.05) in comparison to control group. Our preliminary investigation suggests that microwave exposure may affect the haematological parameters of exposed animals, and calls for further evaluation of specificity and biological significance of these biomarkers of exposure., Istraživanje bioloških pokazatelja djelovanja neionizirajućeg zračenja niskih razina izvršeno je na pokusnim štakorima. Istraživan je utjecaj neprekinutih mikrovalova frekvencije od 2450 MHz i srednje gustoće induciranog polja od 10 mW/cm2 na stanične pokazatelje u perifernoj krvi Wistar štakora. Štakori, 13 tjedana stari, prosjećne tjelesne mase 350 g podijeljeni su u dvije skupine, G1 (N=20) i G2 (N=20). G2 skupina bila je izložena 5 dana u tjednu po 2 sata mikrovalovima, dok je G1 skupina predstavljala kontrolnu skupinu. Pokus je trajao 30 dana. Uzorci krvi uzimani su odmah nakon zračenja 1., 8., 16. i 30. dana pukusa. Određen je i međusobno uspoređen broj crvenih krvnih tjelešaca i ukupni broj bijelih krvnih stanica kao i broj njihovih pojedinih vrsta. Dobiveni rezultati pokazali su da broj crvenih krvnih tjelešaca u mikrovalovima izloženoj skupini nije bio značajno povećan (P>0,05) u odnosu na kontrolnu skupinu. Ukupni broj bijelih krvnih stanica u ozračenoj skupini bio je značajno snižen (P

The ultrastructure and morphometry of the endothelial cells of pectoral mammary gland capillaries of female Wistar rats were studied through the reproductive cycle with an electron microscope and image analyser. Subendothelial spaces were absent in the mammary gland capillaries. The density of pinocytotic vesicles (PV) in the capillaries (number of PV per µm2 of endothelial cytoplasm) was significantly increased during pregnancy, reaching maximum values during lactation, and which subsequently decreased during the post-wening stage. The capillaries showed the maximum changes of PV during pregnancy and lactation, with two- and four-fold increases during the respective periods. The density of mitochondria and the length of marginal folds and microvillus processes were also increased significantly (P>0.05) during pregnancy and lactation. The length of marginal folds and microvillus processes were increased two-fold during the lactating period. It is assumed that the ultrastructural changes of endothelial cells of mammary gland capillaries are closely related during the reproductive cycle, and certainly with the functional demand of the mammary glands., Uporabom elektronskog mikroskopa i analizatora slike istraživane su ultrastruktura i morfometrija endotelnih stanica kapilara grudnih mliječnih žlijezda ženskih Wistar štakora tijekom reprodukcijskog ciklusa. Gustoća pinocitotskih mjehurića (PV) u kapilarama (broj PV po µm2 endotelne citoplazme) značajno je porasla tijekom gravidnosti i dosizala najveće vrijednosti u laktaciji, te postupno opadala u razdoblju nakon odbića. Broj PV povećao se dva puta u gravidnosti, a četiri puta u laktaciji. Gustoća mitohondrija i duljina rubnih nabora i broj mikrovila također su značajno (P>0.05) porasli tijekom graviditeta i laktacije. U laktaciji su duljina rubnih nabora i mikrovila bili dva puta veći. Pretpostavljamo da su ultrastrukturne promjene endotelnih stanica kapilara grudnih mliječnih žlijezda usko povezane sa reprodukcijskim ciklusom, a sigurno su povezane s funkcionalnim potrebama mliječnih žlijezda.