The Place and Role of Vitamins Today

Danas postoje najmanje tri zanimljiva znanstvena područja istraživanja učinaka vitamina, rezultati kojih se pokušavaju iskoristiti i u kliničkoj medicini. To su ispitivanja učinkovitosti nekih vitamina u oksidacijskom stresu, odnosno u prevenciji kardiovaskularnih bolesti. Treće područje važno za opću populaciju određivanje je dnevnog unosa vitamina i kvalitete prehrane u odnosu na očuvanje zdravlja. Za suvremenog čovjeka ipak su najzanimljiviji antioksidacijski učinci pojedinih vitamina, koji će za opću populaciju postati važni onog trenutka kada rezultati randomiziranih kliničkih istraživanja potvrde pozitivne rezultate bazičnih istraživanja in vitro i na pokusnim životinjama. Usprkos često kontroverznim podacima epidemioloških i kliničkih studija, shvaćeno je kako dodatni unos pojedinih vitamina i minerala u dnevnim količinama jednakim ili iznad RDAs nije koristan samo za sprečavanje bolesti povezanih s njihovim deficitom nego i za optimalni razvoj i održavanje fizioloških funkcija i/ili prevenciju nekih degenerativnih bolesti. Upravo ta saznanja uzeta su u obzir pri stvaranju novih DRIs vrijednosti, formuliranih od američke udruge FNB, a koje u SAD u Kanadi vrijede od 1999. godine.There are today at least three interesting scientific areas investigating the effects of vitamins and their results being implemented into the clinical medicine. They include trials of some vitamins\u27 effects in treating antioxidant stress and in prevention of cardiovascular diseases. Another aspect important to general population is determination of daily intake of vitamins and the quality of nutrition (diet) regarding the health preservation. However, the antioxidant effects of vitamins are the most interesting for the contemporary human and these results will become important for general population when the preliminary positive results of in vitro and animal studies get their proof in randomised clinical trials. In spite of often-controversial data of epidemiological and clinical studies, it seems that vitamin and mineral intake in doses equal or even higher than RDA not only benefits prevention of diseases related to their deficiency but also helps optimal development and upkeep of physiologic function and/or prevention of some degenerative diseases. These facts were considered by the American FNB Society in creating new DRIs values, which are valid in US and Canada since 1999

Uloga genskog polimorfizma metaboličkih enzima P450(CYP) kao čimbenika osjetljivosti na učinkovitost i toksičnost lijeka te nastanak karcinoma

The polymorphic P450 (CYP) enzyme superfamily is the most important system involved in the biotransformation of many endogenous and exogenous substances including drugs, toxins, and carcinogens. Genotyping for CYP polymorphisms provides important genetic information that help to understand the effects of xenobiotics on human body. For drug metabolism, the most important polymorphisms are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which can result in therapeutic failure or severe adverse reactions. Genes coding for CYP1A1, CYP1A2, CYP1B1, and CYP2E1 are among the most responsible for the biotransformation of chemicals, especially for the metabolic activation of pre-carcinogens. There is evidence of association between gene polymorphism and cancer susceptibility. Pathways of carcinogen metabolism are complex, and are mediated by activities of multiple genes, while single genes have a limited impact on cancer risk. Multigenic approach in addition to environmental determinants in large sample studies is crucial for a reliable evaluation of any moderate gene effect. This article brings a review of current knowledge on the relations between the polymorphisms of some CYPs and drug activity/toxicity and cancer risk.Među enzimima I. faze biotransformacije sustav citokroma P450 (CYP) prednjači po katalitičkoj svestranosti i pokazuje vrlo visok stupanj polimorfnosti. Istraživanja polimorfizama gena CYP rezultirala su brojnim genetičkim informacijama koje nam pomažu u razumijevanju učinaka ksenobiotika na ljudski organizam. Ova superporodica enzima najvažniji je enzimski sustav uključen u biotransformaciju mnogih endogenih i egzogenih spojeva uključujući lijekove. Za metabolizam lijekova važan je polimorfizam CYP2C9, CYP2C19, CYP2D6 i CYP3A4/5 enzima. Među najvažnije izoforme odgovorne za biotransformaciju različitih kemijskih spojeva a posebno metaboličku aktivaciju prokarcinogena pripadaju CYP1A1, CYP1A2, CYP1B1, CYP2E1. Genska analiza ključnih enzima metabolizma lijekova pomaže u predviđanju terapijskog učinka ili razvoja štetnih nuspojava lijekova. Stoga primjena genotipizacije u kliničkoj praksi pomaže u optimizaciji i individualizaciji terapije i smanjenju medicinskih troškova. Polimorfizam metaboličkih enzima može imati važan učinak na terapiju antidepresivima, antipsihoticima, antikoagulantima, antidijabeticima, antitumorskim lijekovima te lijekovima za liječenje ulkusa i HIV-a. Podaci koje donosi toksikogenomika istražujući individualne predispozicije za karcinogene, teratogene i druge toksičke učinke ksenobiotika, pridonose rasvjetljavanju molekularnih mehanizama kojima kemijski spojevi iz okoliša ili na radnome mjestu utječu na nastanak bolesti u ljudi. Postoje značajni dokazi o povezanosti genskih polimorfizama i osjetljivosti za razvoj karcinoma. Metabolički putovi karcinogenih supstancija su kompleksni, posredovani aktivnošću različitih gena, dok pojedinačni geni najčešće imaju ograničen učinak. Stoga je multigenski pristup, uz uključivanje važnih čimbenika iz okoliša u studijama s velikim brojem ispitanika bitan za pouzdanu procjenu rizika od razvoja karcinoma

Effects of high sucrose diet, gemfibrozil, and their combination on plasma paraoxonase 1 activity and lipid levels in rats

We investigated the influence of high sucrose diet (HSD) after 3 or 5 weeks of administration on paraoxonase 1 (PON1) activity in plasma of normolipidemic rats and the relationship between serum PON1 activity, triacylglycerides (TGs), HDL and total cholesterol vs. the control group of rats fed normal, control diet (CD). Because the data about the influence of gemfibrozil (GEM) on PON1 activity are controversial, we also investigated its effects (administration in the 4th and 5th week in rats on HSD and CD) on plasma PON1 activity and lipid levels in normolipidemic rats, and in rats with hypertriglyceridemia caused by HSD. Our results obtained in rats on HSD show a significant increase of plasma TGs levels by 47% (P<0.05) after 5 weeks of treatment, and PON1 activity by 32% and 23% (P<0.05) after 3 and 5 weeks, but without change in lipid levels vs. rats on CD. In the rats on CD and HSD, GEM caused a significant decrease of PON1 activity by 44% and 33%, while a significant decrease of TGs level by 38% (P<0.05) was measured only in rats on CD. The effects of GEM on total cholesterol, HDL and LDL in both groups of rats were typical for its action on lipoprotein metabolism. Because GEM in the rat liver stimulates proliferation of peroxisomes, β oxidation, and production of H2O2, it is possible that the oxidative stress induced by GEM damages hepatocytes and lowers the synthesis of PON1

Djelovanje cikloheksimida na aktivnost butirilkolinesteraze in vivo

The paper describes the catalytic activity of butyrylcholinesterase (BuChE) measured in plasma, liver, white adipose tissue, heart, and brain of rats intraperitoneally administered a single non–lethal dose of cycloheximide (2.0 mg/kg body weight; CHM). The BuChE assay was performed on rats of both sexes either administered CHM or saline (controls), and killed 2, 3, 4, 5, 10 days later. A significant decrease of BuChE catalytic activity was observed in all tested tissues except plasma. In animals of both sexes, the lowest BuChE catalytic activity was found in the liver (2–6%), while it was higher in white adipose tissue, heart, and brain. However, the respective values remained significantly different from controls (33–67%, 49–62%, and 14–71% in males, and 24–82%, 72–86%, and 33–67% in females). Since there was no effect of CHM on BuChE catalytic activity in plasma, the data suggest that CHM inhibits the synthesis of BuChE rather than its active site.U ovom je istraživanju mjerena katalitička aktivnost enzima butirilkolinesteraze (BuChE) u plazmi, jetri, bijelom masnom tkivu, srcu i mozgu štakora tretiranih jednokratnom intraperitonealnom dozom cikloheksimida (2,0 mg/kg tjelesne težine, CHM). Katalitička aktivnost enzima izmjerena je u navedenim tkivima životinja obaju spolova koje su žrtvovane 2, 3, 4, 5 ili 10 dana nakon primjene CHM–a ili fiziološke otopine (kontrolna skupina). Značajno smanjenje katalitičke aktivnosti enzima BuChE izmjereno je u svim tkivima tretiranih životinja osim u plazmi gdje njegova aktivnost u životinja obaju spolova tijekom cjelokupnog istraživanja nije značajno odstupala od kontrolnih vrijednosti. Preostala katalitička aktivnost BuChE u jetrenome tkivu tretiranih životinja obaju spolova bila je 2–6%, dok je u masnom tkivu, srcu i mozgu aktivnost ovog enzima bila viša negoli u jetri, no statistički značajno različita od aktivnosti u istim tkivima kontrolnih životinja. Katalitička aktivnost BuChE u bijelome masnom tkivu, srcu i mozgu tretiranih mužjaka bila je 33–67, 49–62 i 14–71% u odnosu na aktivnost enzima u tkivima kontrolnih mužjaka, dok je u istim tkivima ženki taj raspon bio 24–82, 72–86 i 33–67%. Butirilkolinesteraza je enzim koji se većim dijelom sintetizira u jetri te izlučuje u cirkulaciju gdje mu je vrijeme polovičnog raspada 8–12 dana. Budući da CHM nije imao učinka na katalitičku aktivnost BuChE u plazmi štakora, a aktivnost enzima u jetri i drugim tkivima u kojima se vjerojatno sintetizira bila je značajno smanjena, može se zaključiti da CHM inhibira sintezu enzima, a ne njegovu katalitičku aktivnost. Stoga aktivnost BuChE u plazmi ne može biti pokazatelj otrovanja cikloheksimidom u ljudi

Correlation between serum butyrylcholinesterase activity and serum lipid concentrations in rats treated with different antagonists of the adrenergic system

Background and Purpose: Based on the facts that the blockade of adrenergic receptors can alter lipid profile in the serum and that it has been suggested that butyrylcholinesterase (BuChE) is involved in lipid metabolism, different adrenergic blocking agents were administered to rats to modify lipid concentrations in serum. The activity of BuChE was examined under such conditions and correlations with serum lipids were investigated. The purpose of this study was to evaluate the effects of different adrenergic antagonists on BuChE activity and to investigate the correlation between BuChE activity and serum lipids. Materials and Methods: Six groups of male Fischer 344 rats (9 animals/ group) were treated orally with adrenergic antagonists (mixed in commercial diet) during 6 weeks: oxprenolol, atenolol, doxazosin, oxprenolol and doxazosin, atenolol and doxazosin, and guanethidine. A control group (9 rats) received only commercial diet. BuChE activity in serum was determined with kinetic color test using butyrylthiocholine as a substrate. Concentrations of serum lipids (total cholesterol, triglycerides and HDL cholesterol) were determined by enzymatic colorimetric tests. Data were analyzed by Kruskal-Wallis test and Spearman’s correlation coefficient. Results: The results revealed that oxprenolol and doxazosin (given alone or in combination with atenolol or oxprenolol) increased (>30 %) BuChE activity. BuChE activity correlated with different serum lipids, and correlation depended on the type of adrenergic blockade. Conclusion: Although the examined adrenergic antagonists did not influence serum lipid concentrations, the increase of BuChE activity and correlation with serum lipid concentrations suggested that the increase of this enzyme’s activity might be the first sign of altered lipid metabolism

Učinak diklorvosa na aktivnost butirilkolinesteraze i metabolizam lipida u štakora

This paper describes the effects of dichlorvos (DDVP) on butyrylcholinesterase (BuChE) activity with possible consequences for lipid and lipoprotein metabolism in rats. The rats of both sexes were given a single and multiple doses of DDVP (8.0 mg/kg body weight) with two–day intervals between administrations, ensuring the continuous inhibition of BuChE activity without lethal outcome. BuChE activity was measured in plasma, liver, and white and brown adipose tissue. The recovery of BuChE activity was observed only in white adipose tissue of female rats 10 days after treatment. Our results show that DDVP significantly decreases BuChE activity in female and male rat plasma (40–60%; P<0.05), and significantly increases triglycerides (60–600%; P<0.05) and total cholesterol (35–75%; P<0.05). In contrast to the increased HDL–cholesterol (20–30%; P<0.05), LDL–cholesterol decreased (30–40%; P<0.05). The decrease of BuChE activity and the changes in concentrations of lipids and lipoproteins were observed throughout the experiment. Our results contribute to the hypothesis that BuChE may play a role in lipid and lipoprotein metabolism.U radu su opisani učinci diklorvosa (DDVP) na aktivnost enzima butirilkolinesteraze (BuChE) i metabolizam lipida i lipoproteina u štakora obaju spolova. Učinci DDVP–a u dozi od 8,0 mg/kg tjelesne težine istraživani su poslije primjene jedne i dviju intraperitonealnih aplikacija. Kod ponovljenih aplikacija DDVP je davan svakih 48 sati kako bi se osigurala kontinuirana inhibicija BuChE u tretiranih životinja, ali bez pojave smrtnosti životinja. Aktivnost BuChE izmjerena je u plazmi, jetri te bijelome i smeđem masnom tkivu. Oporavak aktivnosti BuChE uočen je samo u bijelom masnom tkivu ženki štakora koje su žrtvovane 10 dana nakon zadnjeg tretmana. Nađeno je da DDVP značajno smanjuje aktivnost BuChE u plazmi životinja obaju spolova (40–60%; P<0,05) te značajno povećava koncentraciju triglicerida (60–600%; P<0,05) i ukupnog kolesterola (35–75%; P<0,05). Za razliku od povećane vrijednosti HDL–kolesterola (20–30%; P<0,05) uočen je statistički značajan pad koncentracije LDL–kolesterola (30–40%; P<0,05). Aktivnosti BuChE, kao i promjene u koncentracijama lipida i lipoproteina primijećene su tijekom cijelog eksperimenta. Naši rezultati govore u prilog hipotezi da BuChE ima važnu logu u metabolizmu lipida i lipoproteina in vivo

Učinak diklorvosa na aktivnost butirilkolinesteraze i metabolizam lipida u štakora

This paper describes the effects of dichlorvos (DDVP) on butyrylcholinesterase (BuChE) activity with possible consequences for lipid and lipoprotein metabolism in rats. The rats of both sexes were given a single and multiple doses of DDVP (8.0 mg/kg body weight) with two–day intervals between administrations, ensuring the continuous inhibition of BuChE activity without lethal outcome. BuChE activity was measured in plasma, liver, and white and brown adipose tissue. The recovery of BuChE activity was observed only in white adipose tissue of female rats 10 days after treatment. Our results show that DDVP significantly decreases BuChE activity in female and male rat plasma (40–60%; P<0.05), and significantly increases triglycerides (60–600%; P<0.05) and total cholesterol (35–75%; P<0.05). In contrast to the increased HDL–cholesterol (20–30%; P<0.05), LDL–cholesterol decreased (30–40%; P<0.05). The decrease of BuChE activity and the changes in concentrations of lipids and lipoproteins were observed throughout the experiment. Our results contribute to the hypothesis that BuChE may play a role in lipid and lipoprotein metabolism.U radu su opisani učinci diklorvosa (DDVP) na aktivnost enzima butirilkolinesteraze (BuChE) i metabolizam lipida i lipoproteina u štakora obaju spolova. Učinci DDVP–a u dozi od 8,0 mg/kg tjelesne težine istraživani su poslije primjene jedne i dviju intraperitonealnih aplikacija. Kod ponovljenih aplikacija DDVP je davan svakih 48 sati kako bi se osigurala kontinuirana inhibicija BuChE u tretiranih životinja, ali bez pojave smrtnosti životinja. Aktivnost BuChE izmjerena je u plazmi, jetri te bijelome i smeđem masnom tkivu. Oporavak aktivnosti BuChE uočen je samo u bijelom masnom tkivu ženki štakora koje su žrtvovane 10 dana nakon zadnjeg tretmana. Nađeno je da DDVP značajno smanjuje aktivnost BuChE u plazmi životinja obaju spolova (40–60%; P<0,05) te značajno povećava koncentraciju triglicerida (60–600%; P<0,05) i ukupnog kolesterola (35–75%; P<0,05). Za razliku od povećane vrijednosti HDL–kolesterola (20–30%; P<0,05) uočen je statistički značajan pad koncentracije LDL–kolesterola (30–40%; P<0,05). Aktivnosti BuChE, kao i promjene u koncentracijama lipida i lipoproteina primijećene su tijekom cijelog eksperimenta. Naši rezultati govore u prilog hipotezi da BuChE ima važnu logu u metabolizmu lipida i lipoproteina in vivo

Učinci simvastatina i fenofibrata na malondialdehid i reducirani glutation u plazmi, jetri i mozgu normolipidemičnih i hiperlipidemičnih štakora

The objective of study was to investigate the effects of different doses of simvastatin and fenofibrate on malondialdehyde (MDA) and reduced glutathione (GSH) in the plasma, liver, and brain tissue of male normolipidaemic and hyperlipidaemic rats. Normolipidaemic (Wistar) rats were receiving 10 or 50 mg/kg a day of simvastatin or 30 or 50 mg/kg a day of fenofibrate. Hyperlipidaemic (Zucker) rats were receiving 50 mg/kg/day of simvastatin or 30 mg/kg/day of fenofibrate. Control normolipidaemic and hyperlipidaemic rats were receiving saline. Simvastatin, fenofibrate, and saline were administered by gavage for three weeks. In normolipidaemic rats simvastatin and fenofibrate showed similar and dose-independent effects on plasma and brain MDA and GSH concentrations. Generally, plasma and brain MDA decreased, while brain GSH concentration increased. In hyperlipidaemic rats simvastatin did not affect plasma and brain MDA and GSH concentrations but significantly decreased liver GSH. Fenofibrate decreased plasma and liver MDA but increased brain MDA. In both rat strains fenofibrate significantly decreased liver GSH concentrations, most likely because fenofibrate metabolites bind to GSH. Our findings suggest that simvastatin acts as an antioxidant only in normolipidaemic rats, whereas fenofibrate acts as an antioxidant in both rat strains.Cilj ovog istraživanja bio je istražiti učinke različitih doza simvastatina i fenofibrata na malondialdehid (MDA) i reducirani glutation (GSH) u plazmi, jetri i mozgu mužjaka normolipidemičnih (Wistar) i hiperlipidemičnih (Zucker) štakora. Na prvim dvjema eksperimentalnim skupinama normolipidemičnih štakora simvastatin je primijenjen u dozama 10 ili 50 mg/kg dnevno, a fenofibrat na trećoj i četvrtoj skupini u dozama od 30 i 50 mg/kg/dan. Prva eksperimentalna skupina hiperlipidemičnih štakora primala je simvastatin 50 mg/kg/dan, a druga fenofibrat 30 mg/kg/dan. Kontrolne skupine normolipidemičnih i hiperlipidemičnih štakora primale su fiziološku otopinu. Simvastatin, fenofibrat i fiziološka otopina primjenjivani su oralno tijekom tri tjedna. U plazmi i mozgu normolipidemičnih štakora simvastatin I fenofibrat pokazali su slične i o dozi neovisne učinke na koncentracije MDA i GSH. Općenito, MDA je bio smanjen, a koncentracija GSH bila je povećana. U hiperlipidemičnih štakora simvastatin nije utjecao na koncentraciju MDA i GSH, ali je prouzročio značajno smanjenje GSH u jetri. Fenofibrat je smanjio MDA u plazmi i jetri te povećao MDA u mozgu. U oba soja štakora fenofibrat je značajno smanjio koncentraciju GSH u jetri, vjerojatno zbog konjugacije GSH s nekim metabolitima fenofibrata. Prema našim rezultatima, simvastatin djeluje antioksidacijski samo u normolipidemičnih štakora, a antioksidacijski učinak fenofibrata prisutan je u oba soja

Učinci simvastatina i fenofibrata na aktivnost butirilkolinesteraze u mozgu, plazmi i jetri normolipidemičnih i hiperlipidemičnih 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<0,001). Povećanje aktivnosti BuChE u plazmi i jetri nakon primjene SIMV i FENO izmjeren je u oba soja štakora bez obzira na to je li korišten ACTh ili BTCh. U većini slučajeva povećanje aktivnosti BuChE u plazmi i jetri bilo je značajno. S obzirom na važnu ulogu BuChE u kolinergičnom prijenosu te na njezinu farmakološku funkciju, potrebno je nastaviti istraživanja utjecaja antilipidnih lijekova na aktivnost BuChE

Učinak deksametazona na aktivnost butirilkolinesteraze i lipide plazme u štakora

The paper describes the effect of glucocorticoide dexamethasone (DM) given intraperitoneally on the catalytic activity of butyrylcholinesterase (BuChE) measured in plasma, liver and white adipose tissue of rats of both sexes. Effects of DM on the concentration of plasma lipids and lipoproteins were also tested. Rats were given multiple (2 and 4) pharmacological doses (0.4 and 3.0 mg kg-1 body mass) of DM. All animals were sacrificed 48 h after the last dose. Administration of DM significantly decreased the catalytic activity of BuChE in plasma and liver of all treated groups regardless of sex. BuChE catalytic activity in white adipose tissue differed depending on the dose and frequency of administration. In contrast to liver where both doses caused significant BuChE inhibition, the lower DM dose did not inhibit BuChE activity in adipose tissue, and the inhibition achieved by the higher dose was not as strong as in liver. This result corroborates an earlier hypothesis that BuChE is also synthesized in the adipose tissue. DM significantly increased plasma concentrations of triglycerides, total cholesterol and high-density lipoprotein (HDL) cholesterol and decreased the low-density lipoprotein (LDL) cholesterol concentration. Neither positive correlation between BuChE and triglycerides nor negative correlation between BuChE and HDL was found. Changes in lipid profile during DM treatment were not sex- and time-dependent.U radu su opisani učinci glukokortikoida deksametazona (DM) na katalitičku aktivnost butirilkolinesteraze (BuChE) u plazmi, jetri i bijelom masnom tkivu štakora oba spola. Ispitan je i učinak DM na koncentracije plazmatskih lipida i lipoproteina. Štakori su tretirani višekratno (2 i 4 puta) farmakološkim dozama (0,4 i 3,0 mg kg–1 tjelesne mase) DM koji je primijenjen intraperitonealno. Životinje su žrtvovane 48 sati nakon što su primile zadnju dozu. Utvrđeno je da DM značajno snižava katalitičku aktivnost BuChE u plazmi i jetri štakora oba spola. Rezultati katalitičkih aktivnosti BuChE u bijelom masnom tkivu bili su različiti ovisno o veličini doze i broju aplikacija. Za razliku od jetre, gdje su obje doze izazvale značajnu inhibiciju BuChE, u masnom tkivu niža doza nije inhibirala aktivnost enzima, a inhibicija s višom dozom nije bila tako snažna kao u jetri. Rezultati govore u prilog hipotezi da se BuChE osim u jetri sintetizira i u masnom tkivu. Također je utvrđeno da DM značajno povećava koncentraciju triglicerida, ukupnog kolesterola i HDL-kolesterola, te smanjuje koncentraciju LDL-kolesterola u plazmi. Međutim, nije utvrđena pozitivna korelacija između BuChE i triglicerida, niti negativna korelacija između BuChE i HDL. Promjene koncentracija lipidnih frakcija tijekom primjene DM nisu ovisile o spolu eksperimentalnih životinja niti o trajanju pokusa