The influence of diet, smoking, alcohol and drugs on the metabolism of xenobiotics

U svakoj situaciji čovjek je istodobno izložen raznim egzogenim, tijelu stranim kemijskim supstancijama, ksenobioticima. Toksičnost pojedine tvari ne ovisi samo o njezinim toksikološkim značajkama (toksikokinetika, toksikodinamika) nego je i funkcija izložene biološke vrste, aktivnosti enzima koja je genetski predodređena te faktora okoline uključujući istodobnu izloženost drugim ksenobioticima, mikroklimatske uvjete (temperatura, vlaga, tlak), kao i životne navike (način prehrane, pušenje, konzumiranje alkohola, upotreba lijekova itd.). Spoznaja o svim tim faktorima kao mogućim uzrocima velikih interindividualnih razlika u biološkim pokazateljima pri jednakoj razini profesionalne izloženosti nekoj kemijskoj noksi direktan je povod nastanka ovog prikaza. Iz raznovrsnog i kompleksnog područja interakcije, gdje se ne može predvidjeti ni kvalitativno ni kvantitativno djelovanje pojedinog sastojka smjese izdvojeni su i u ovom prikazu opisani dostupni rezultati istraživanja utjecaja načina prehrane, navike pušenja, konzumiranja alkohola i upotrebe lijekova, dakle nekih životnih navika na metabolizam ksenobiotika. Razmatrajući tu temu potrebno je prvo istaknuti osnovne značajke metabolizma ksenobiotika odnosno aktivnosti metaboličkih enzima. Oskudan broj radova koji istražuju interakciju najbolje odražava činjenica da je uvodni dio o metabolizmu opsežniji od opisa utjecaja životnih navika na metabolizam ksenobiotikaThe paper is a survey of available results on the impact of main life-style factors (dietary and smoking habits, alcohol ingestion, use of drugs) on the metabolism of xenobiotics. The principal characteristics of the metabolism -and the activity of metabolic enzymes are described. The relatively scanty number of examples, which could be justified by the variety and complexity of combined exposure, allows to conclude that life-style factors have considerable influence on interindividual differences in susceptibility to xenobiotics toxicity

A methodological approach to estimating the toxicity of chemical substances

Sve se češće čuje mišljenje da je danas opasnost od kemijskih supstancija (ksenobiotika) jednaka onoj od prije stotinu godina od bakterija. Povećanjem spoznaje o opasnosti od kemikalija postavlja se pitanje boljeg osiguranja prihvatljivog rizika. U tu svrhu iznesene su neke zakonske regulative u svijetu d u nas, te osnovni problemi provedbe toksikološkog ispitivanja počevši od izbora eksperimentalnih životinja i uniformnosti provođenja toksikoloških pokusa.The risk of chemical substances (xenobiotics) is claimed more and more often to be as great today as was the danger of bacterias a hundred years ago. Greater awareness of chemical hazards creates in turn the need for greater safety from acceptable risks. In view of this relevant legislative regulations in Yugoslavia and in other countries are presented and basic problems encountered in carrying out toxicological investigations, from the very choice of experimental animals to uniform conductance of experiments, are discussed

The estimation of exposure to fluorides in the workplace

U svrhu ocjene opterećenja tijela plinovitim fluoridima i fluoridima u obliku čestica u uvjetima profesionalne izloženosti pri elektrolitskoj ekstrakciji aluminija, provođena su tijekom 7 godina mjerenja osobne izloženosti fluoridima (odvojeno plinovitim od onih u obliku čestica), kao i sadržaj fluorida u mokraći 159 izloženih radnika u odnosu na kontrolnu skupinu, Istraživanja su pokazala da je u izloženih. radnika sadržaj fluorida u mokraći značajno veći negoli u kontrolnoj skupini. Razina fluorida u mokraći prije rada, kao li razlika u razini prije i nakon završetka rada u značajnoj je korelacija u razinama plinovitih fluorida kojima su radnici bili izloženi.To estimate the body burden of gaseous fluorides and fluoride particles in conditions of occupational exposure du-ring the electrolytic extraction of aluminium measurements of personal exposure to fluorides (separately to gaseous fluorides and to fluoride particles) and of fluoride urinary content were conducted in a group of 159 occupationally exposed workers and in a control group over a period of seven years. The urinary content of fluorides in exposed workers was significantly higher than in the control group. The fluoride level in urine before work and the difference in fluoride levels before and after work were in good correlation with the levels of gaseous fluorides to which the workers had been exposed

The determination of paraquat in biological material

Opisano je suicidalno otrovanje izuzetno velikom količinom parakvata (otprilike osam puta većom od procijenjene smrtonosne doze za čovjeka) sa smrtnim ishodom u toku liječenja. Uzeti su za analizu uzorci mokraće, krvi i hemodijalizata 7, 8, 10 i 12 sati nakon ingestije, Na obdukciji uzeti su uzorci bubrega, jetre i pluća. U uzorcima mokraće, krvi i hemodijalizata utvrđeno je postepeno smanjivanje koncentracije parakvata. Najveća koncentracija parakvata određena je u bubregu, nešto niža u jetrima, a najniža u plućima.The case described is one of poisoning with an exceptionally large quantity of paraquat (about eight times larger than the estimated lethal dose for man) in a suicide attempt with a fatal consequence. Samples of urine, blood and haemodialysates were taken 7, 8, 10 and 12 hours after ingestion, and later on post mortem samples were taken· of the kidneys, liver and lungs. In the samples of urine, blood and haemodialysates a gradual decrease in the concentration of paraquat was observed depending on the time of sampling. The maximum paraquat concentration in the organs was found in the kidneys, a slightly lower in the liver and the lowest in the lungs

Odabir bioloških pokazatelja pri profesionalnoj izloženosti toluenu i ksilenu

Results of a comparative study of occupational exposure to toluene and xylene are presented. The study was carried out in a group of 24 workers from a paint factory and aimed to determine the most appropriate exposure indicators for use in biological monitoring. Measurements included toluene and xylene in blood and their metabolites in urine. Toluene in blood proved to be the best indicator of toluene exposure, and both xylene in blood and its only major metabolite methylhippuric acid in urine to be reliable indicators of xylene exposure, The validity of hippuric acid and o-cresol as toluene exposure indicators has not been confirmed.Proveđeno je komparativno istraživanje profesionalne izloženosti toluenu i ksilenu radi odabira najpogodnijih bioloških pokazatelja u biološkom monitoringu. Određeni su toluen i ksilen u krvi i njihovi metaboliti u urinu 24-ju radnika profesionalno izloženih toluenu i ksilenu. Toluen u krvi pokazao se najboljim pokazateljem izloženosti toluenu, dok su i ksilen u krvi i njegov glavni metabolit metilhipurna kiselina pouzdani pokazatelji izloženosti ksilenu. Vrijednosti hipurne kiseline odnosno o-krezola nisu jednoznačni pokazatelji izloženosti toluenu što je poznato iz ranijih istraživanja a potvrđeno je i našim mjerenjima

Event-Related Potentials in Medical Workers with Long-Term Exposure to Xylene

The effects of chronic exposure to xylene on cognitive ability were studied in a group of 35 medical workers occupationally exposed to low-level concentrations of xylene for at least five years by using event-related potentials (ERPs), and compared with a control group of 21 subjects. The exposure to xylene was confirmed through determination of m-methylhippuric acid, a reliable biological indicator of xylene exposure, in pre- and post-shift urine. A dose-effect relationship between log m-methylhippuric acid and ERP log latency (p = 0.032), and the ERP amplitude (p = 0.047) was statistically significant. The group of medical workers showed significantly longer ERP log latency (p < 0.001) than did the control group with respect to factors of exposure to smoking, education and age as covariates. For the ERP amplitude the difference was found not to be significant (p = 0.263), probably due to high between subject variability. The cognitive impairment may occur in workers chronically exposed to xylene

The relationship between the methods for the determination of erythrocyte protoporphyrins (EP) and zinc protoporphyrins (ZPP)

U svrhu izbora najprikladnije metode za određivanje eritrocitnog protoporfirina (EP), vrlo važnog biokemijskog pokazatelja u ocjeni povećane apsorpcije olova, ispitan je odnos između spektrofluorometrijske metode Chisolm-Brown i spektrofotometrijske metode Cripps-Peters za određivanje EP, kao i odnos između obje metode s direktnim određivanjem cink-protoporfirina (ZPP) na hematofluorometru. S pomoću koeficijenta korelacije utvrđena je značajna povezanost između sve tri ispitane metode. S pomoću pravca regresije utvrđena je veća osjetljivost spektrofluorometrijske metode Chisolm-Brown od spektrofotometrijske metode Cripps-Peters za određivanje EP. Metoda direktnog određivanja ZPP na hematofluorometru je također osjetljivija od spektrofotometrijske metode Cripps-Peters. Dokazano je da je spektrofluorometrijska metoda Chisolm-Brown specifična, točna, osjetljiva i ponovljiva. Pored toga je relativno brza i lako izvediva, ne zahtijeva veliku količinu biološkog uzorka i kompliclrane tehničke uređaje. Zbog tih osobina preporučuje se kao metoda izbora za određivanje EP u odraslih i djece za ispitivanje povećane apsorpcije olova, sideropenične anemije te u nekim genetskim bolestima poremećene sinteze porfirina.In order to find the most convenient method for erythrocyte protoporphyrin (EP) determination, a very important biochemical parameter in the evaluation of increased lead absorption, the relationship between the Chisolm-Brown spectrofluorometric method and the Cripps-Peters spectrophotometric method for EP determination, as well as the relationship between the two methods and direct zinc-protoporphyrin (ZPP) determination by means of a haematofluorometer were examined. A very significant connection between all the three examined methods was established by means of the correlation coefficient. From the regression line the sensitivity of the Chisolm-Brown spectrofluorometric method was found to be higher than of the Cripps-Peters method for EP. The method of direct ZPP determination also proved to be more sensitive than the Cripps-Peters spectrophotometric method. The Chisolm-Brown spectrofluorometric method was shown to be specific, acourate, sensitive and reproducible. In addition, it is relatively quick and easy to apply, does not need a large quantity of biological samples and complicated technical instruments. Because of these characteristics it is recommended as a method of choice for EP determination in adults and children for examination of increased lead absorption, sideropenic anaemia and in some genetic diseases of disturbed porphyrin synthesis