Promjene citokroma P450 jetre i mozga nakon višekratne primjene kokaina, samog ili u kombinaciji s nifedipinom

The objective of this study was to evaluate possible changes caused by multiple cocaine administration, alone and in combination with 1,4-dihydropiridine calcium channel blocker nifedipine, on cytochrome P450 levels both in the brain and liver. The experiment was done on male Wistar rats divided in four groups: control, treated with nifedipine (5 mg kg-1 i.p. for five days), treated with cocaine (15 mg kg-1 i.p. for five days), and treated with nifedipine and 30 minutes later with cocaine (also for five days). Total cytochrome P450 was measured spectrometrically in liver and brain microsomes. Multiple administration of cocaine alone and in combination with nifedipine did not change the brain P450 significantly. In the liver, nifedipine significantly increased P450 by 28 % vs. control. In contrast, cocaine significantly decreased P450 by 17 % vs. control. In animals treated with nifedipine and cocaine, cytochrome P450 increased 11 % (p<0.01) vs. control, decreased 12.5 % (p<0.001) vs. nifedipine group and increased 34 % (p<0.0001) vs. cocaine group. These results suggest that the cocaine and nifedipine interact at the metabolic level.Cilj je ovog istraživanja bio ocijeniti moguće promjene uzrokovane višestrukom primjenom kokaina kao jedinog agensa odnosno u kombinaciji s nifedipinom, 1,4-dihidropiridinskim blokatorom kalcijevih kanala, na razine citokroma P450 u mozgu i jetri štakora. Životinje (mužjaci Wistar štakora) podijeljene su u četiri skupine: kontrolnu skupinu, skupinu koja je primala nifedipin (5 mg kg-1 ip. pet dana), skupinu koja je primala kokain (15 mg kg-1 ip. pet dana) i skupinu koja je primala nifedipin te pola sata kasnije kokain (također pet dana). Ukupna količina citokroma P450 mjerena je spektrofotometrijski u mikrosomima jetre i mozga. Višestruka primjena samo kokaina odnosno u kombinaciji s nifedipinom nije značajno promijenila razine citokroma P450 u mozgu. U jetri je međutim nifedipin u odnosu na kontrolnu skupinu uzrokovao povišenje razina P450, za statistički značajnih 28 %. Kokain je uzrokovao statistički značajan pad razine P450 za 17 % u odnosu na kontrolnu skupinu. U životinja koje su primale kombinaciju nifedipina i kokaina razina citokroma P450 narasla je za 11 % (p<0.01) u odnosu na kontrolu, bila je 12.5 % (p<0.001) niža u odnosu na skupinu koja je primala nifedipin te viša za 34 % (p<0.0001) u odnosu na skupinu koja je primala samo kokain. Rezultati ovog istraživanja upućuju na interakcije ovih spojeva koje se odvijaju na razini metabolizm

Forty years literature review of primary lung lymphoma

There are several unresolved issues through out the literature regarding the entity of primary lung lymphoma. Extensive literature review of this uncommon pathology is carried out

Protective effect of diallyl sulfide against benzene induced chemical carcinogenesis in kidney

Abstract Not Availabl

Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and associated drug metabolizing enzyme activities in rabbit liver

The effects of diabetes on cytochrome P450 (CYP)-dependent drug metabolizing enzymes are yet to be clarified. The most widely used animals in these studies have been rats, and information on the effects of diabetes on rabbit liver drug metabolizing enzymes have been unavailable until now. In this study, for the first time, a significant induction of liver CYP2E1 is demonstrated via immunoblot analysis in alloxan-induced rabbits. The CYP2E1 content of diabetic microsomes was highly correlated with the activities of liver aniline 4-hydroxylase (r=0.82, p < 0.05), and p-nitrophenol hydroxylase (r=0.86, p < 0.01), and diabetes increased the activities of the enzymes associated with CYP2E1. The activities of aniline 4-hydroxylase and p-nitrophenol hydroxylase were significantly increased by 1.7 and 1.8-fold, respectively compared to those of control rabbits. In marked contrast, diabetes had no effect on the protein levels of CYP2B4 as determined by immunoblotting and on benzphetamine N-demethylase activity, which is known to be specifically metabolized by CYP2B4 in rabbit liver. The present study demonstrates that diabetes increases the activities of CYP2E1 and associated enzymes but does not change the activity levels of CYP2B4 and associated enzymes in diabetic rabbits. These findings are in contrast to those of mice, hamsters and rats, and that suggest the presence of species-dependent responses of CYP-dependent drug metabolizing enzymes to diabetes

STABILITY AND STORAGE-CONDITIONS OF NADH-CYTOCHROME B5 REDUCTASE CROSS-LINKED INTO GELATIN BY CHROMIUM(III) ACETATE

NADH-cytochrome b5 reductase was isolated and partially purified from rabbit liver microsomes. It was immobilized into gelatin by chemical cross-linking. Chromium (III) acetate was used as cross-linker. The effects of pH and temperature on the immobilized cytochrome b5 reductase were investigated. The reusability and storage stability of immobilized enzyme were also tested. Immobilized NADH-cytochrome b5 reductase activities were found to be stable for at least 72 d and 24 uses. The storage stability of NADH-cytochrome b5 reductase was improved with immobilization at 25 degrees C

IMMOBILIZATION OF NADH-CYTOCHROME B5 REDUCTASE INTO GELATIN BY CROSS-LINKING

In this work NADH-cytochrome b5 reductase enzyme (EC 1.6.2.2) obtained from rabbit liver microsomes was immobilized into gelatin by crosslinking. Chromium (III) acetate and chromium (III) sulfate were used as crosslinkers. To find the most suitable immobilization parameters; effect of crosslinker, enzyme and gelatin concentrations on immobilized enzyme activity were investigated. Unbounded enzyme was determined by washing experiments