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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.

The study objective was to test the hypothesis that simvastatin and fenofibrate should cause an increase in butyrylcholinesterase (BuChE) activity not only in the plasma and liver but also in the brain of normolipidemic and hyperlipidemic rats. Catalytic enzyme activity was measured using acetylthiocholine (ATCh) and butyrylthiocholine (BTCh) as substrates. Normolipidemic and hyperlipidemic rats were divided in four groups receiving 50 mg/kg of simvastatin a day or 30 mg/kg of fenofibrate a day for three weeks and three control groups receiving saline. Simvastatin and fenofibrate caused an increase in brain BuChE activity in both normo- and hyperlipidemic rats regardless of the substrate. The increase with BTCh as substrate was significant and practically the same in normolipidemic and hyperlipidemic rats after simvastatin treatment (14–17% vs controls). Simvastatin and fenofibrate also increased liver and plasma BuChE activity in both normolipidemic and hyperlipidemic rats regardless of the substrate. In most cases the increase was significant. Considering the important role of BuChE in cholinergic transmission as well as its pharmacological function, it is necessary to continue investigations of the effects of lipid-lowering drugs on BuChE activity., Cilj ispitivanja bio je u normolipidemičnih i hiperlipidemičnih štakora potvrditi pretpostavku da simvastatin (SIMV) I fenofibrat (FENO) ne uzrokuju samo povećanje aktivnosti butirilkolinesteraze (BuChE) u plazmi i jetri nego i povećavaju aktivnosti BuChE u mozgu. Katalitička aktivnost enzima mjerena je upotrebom acetiltiokolina (ATCh) i butiriltiokolina (BTCh) kao supstrata. Normolipidemični i hiperlipidemični štakori raspoređeni su u eksperimentalne skupine, koje su tri tjedna primale SIMV 50 mg/kg na dan ili FENO 30 mg/kg na dan, dok su kontrolne skupine primale fiziološku otopinu. I SIMV i FENO uglavnom su izazvali povećanje aktivnosti BuChE u mozgu obaju sojeva štakora bez obzira na korišteni supstrat. Aktivnosti BuChE mjerene BTCh kao supstratom bile su značajno veće u odnosu na kontrolne vrijednosti u mozgu normolipidemičih štakora nakon primjene SIMV te u mozgu hiperlipidemičnih štakora nakon primjene obaju agensa (14‒17%, p

Cypermethrin and beta-cyfluthrin are two most widely used multipurpose pyrethroids. After determining their oral LD50 (416.98 mg kg-1 and 354.8 mg kg-1 body weight, respectively), we assessed their hepatotoxicity in Wistar rats following acute (0.1 LD50 for 1 day) and sub-acute (0.1 LD50 for 7, 14, 21 or 28 days) poisoning. The assessment was based on hepatic marker enzymes AST, ALT, LDH, ALP, glycogen, total proteins, total lipids, cholesterol, free fatty acids, and phospholipids. AST, ALT, LDH, total lipids, cholesterol, phospholipids, and free fatty acids in hepatic homogenate increased following pyrethroid stress. In contrast, hepatic proteins, glycogen, and ALP activity decreased due to lysis of structural proteins and leakage of enzymes into the blood stream. Biochemical data were consistent with histological alterations (cytoplasmic vacuolisation, nuclear polymorphism, eccentric nucleus, karyolysis, karyorrhexis, and sinusoidal dilation). Comparatively greater hepatocellular damage was noted in beta-cyfluthrin than in cypermethrin-treated rats, which is probably related to the fluorine atom in beta-cyfluthrin., Primjena piretroida cipermetrina i beta-ciflutrina veoma je raširena diljem svijeta. Nakon što smo odredili njihov LD50 (416,98 mg kg-1, odnosno 354,8 mg kg-1 tjelesne mase) ispitali smo njihovu toksičnost u jetrima Wistar štakora koji su primili jednokratnu akutnu (0,1 LD50), odnosno odgovarajuće subakutne doze pesticida (0,1 LD50 kumulativno tijekom 7, 14, 21, odnosno 28 dana). Za markere toksičnosti uzeli smo jetrene enzime AST, ALT, LDH, ALP, glikogen, ukupne proteine, ukupne lipide, kolesterol, slobodne masne kiseline te fosfolipide. Razine AST-a, ALT-a, LDH-a, ukupnih lipida, kolesterola, fosfolipida i slobodnih masnih kiselina u homogenatu jetara bile su povišene u štakora izloženih piretroidima u odnosu na kontrolne štakore. S druge strane, razine proteina, glikogena i ALP-a bile su niže, vjerojatno zbog lize strukturnih proteina i curenja enzima u krvotok. Biokemijski nalazi potvrdili su histološke promjene na jetrima poput vakuolizacije citoplazme, polimorfi zama jezgara, ekscentričnih jezgara, kariolize, karioreksije i sinusoidnih proširenja. Beta-ciflutrin se pritom pokazao toksičnijim od cipermetrina, što je vjerojatno povezano s prisutnosti atoma fluora u beta-ciflutrinu.

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.

This recent basic research study used an animal model protocol to assess specific biomarkers of the effect of non-ionising, non-thermal radiation (2450 MHz microwave radiation at 5–15 mW/cm2) on bone marrow, peripheral blood, and bronchoalveolar free cell populations. Of 40 male Wistar rats taken in the study, 20 animals of the experimental group were irradiated for 2 hours a day, 5 days a week, and subsequently killed on days 1, 8, 16, and 30 of the experiment. The remaining 20 rats served as control. All animals were previously intratracheally instilled with biologically inert microspheres to see the influence of irradiation on lung retention kinetics. The cell response to chosen electromagnetic irradiation was followed quantitatively and qualitatively using the standard laboratory methods. The results of peripheral blood cell response suggested a decreasing tendency in total leukocyte count and in relative lymphocyte count in the treated group. A slight increase was also observed in granulocyte count and in the absolute count of peripheral blood erythrocytes over control animals., Ovo pilotsko istraživanje provedeno je na animalnom modelu s namjerom da se uoče specifični biomarkeri učinka neionizirajućeg, netermalnog zračenja (2450 MHz, 5–15 mW/cm2) na stanice koštane srži, periferne krvi i slobodnu staničnu populaciju pluća. U pokus smo uzeli 40 štakora mužjaka soja Wistar, od kojih je kontrolna skupina imala 20 životinja. Pokusnu skupinu životinja zračili smo 2 sata na dan, 5 dana u tjednu. Zatim su životinje žrtvovane 1, 8, 16. i 30. dana pokusa. Svaka je životinja prije početka pokusa intratrahealno instilirana biološki inaktivnim česticama kako bismo dobili uvid u utjecaj zračenja na njihovu retenciju u plućima. Kvantitativni i kvalitativni stanični odgovor na izabrano zračenje pratili smo standardnim laboratorijskim metodama. U usporedbi s kontrolnim životinjama, rezultati staničnog odgovora u perifernoj krvi pokazuju tendenciju snižavanja ukupnog broja leukocita, ali i relativnog broja limfocita u tretiranih životinja te lagano povišenje broja granulocita i apsolutnog broja eritrocita.