rss_2.0Interdisciplinary Toxicology FeedSciendo RSS Feed for Interdisciplinary Toxicology Toxicology Feed meta-analysis of medicinal plants to assess the evidence for toxicity<abstract xml:lang="en"><title style='display:none'>A meta-analysis of medicinal plants to assess the evidence for toxicity</title><p>Toxicity of phytochemicals, plant-based extracts and dietary supplements, and medicinal plants in general, is of medical importance and must be considered in phytotherapy and other plant uses. We show in this report how general database analyses can provide a quantitative assessment of research and evidence related to toxicity of medicinal plants or specific phytochemicals. As examples, several medicinal plants are analyzed for their relation to nephrotoxicity and hepatotoxicity. The results of analyses in different databases are similar, and reveal the two best-established toxic effects among the group of plants that were examined: nephrotoxicity of <italic>Aristolochia fangchi</italic> and hepatotoxicity of <italic>Larrea tridentata.</italic></p></abstract>ARTICLEtrue<abstract xml:lang="en"><title style='display:none'>Editorial</title><p>The year 2010 is not gone yet but we already know that this year will be associated with one of the biggest losses in pharmacology and toxicology. On Tuesday, April 13, 2010, at the age of 97, one of the most influential pharmacologists in Eastern Europe, Professor Helena Rašková has left us. Her wisdom, generosity, kindness and hard work made it possible to create a positive environment for research and education, although sometimes she had to fight hard. Her incredible story "How I became a Pharmacologist" wroted by Prof. Rašková herself documents how rich and inspirational her life was [Rašková H. (1997). Pharmacology &amp; Toxicology 80: 255-261]. In this issue you will find mostly works of her colleagues and friends who would like to pay homage to the mother and grandmother of Czecho-Slovak pharmacology and toxicology and to the wonderful person who Prof. Helena Rašková was. She touched many people in her lifetime, affected many and will truly be missed.</p></abstract>ARTICLEtrue effect of manganese in cadmium-induced hepatic oxidative damage, changes in cadmium distribution and trace elements level in mice<abstract xml:lang="en"><title style='display:none'>Protective effect of manganese in cadmium-induced hepatic oxidative damage, changes in cadmium distribution and trace elements level in mice</title><p>Oxidative tissue damage is considered an early sign of cadmium (Cd) toxicity and has been linked with carcinogenesis. Manganese(II) - at low doses, was found to act as a potent antioxidant against oxidative stress in different in vitro systems producing lipid peroxidation conditions. The present study investigates in vivo antioxidant effects of Mn<sup>2+</sup> pretreatment in acute Cd intoxication with regard to lipid peroxidation, antioxidant defense system and cadmium distribution in the tissues of mice. Four groups of male mice (n=7-8) were used: Cd group was injected sc a single dose of CdCl<sub>2</sub> · 2 1/2 H<sub>2</sub>O (7 mg/kg b.w.); Cd+Mn group was treated <italic>ip</italic> with MnCl<sub>2</sub> · 4H<sub>2</sub>O (20 mg/kg b.w.) 24 hours before Cd intoxication; Mn group received manganese treatment only; Control group received saline only. Twenty-four hours after Cd intoxication an increased lipid peroxidation (<italic>p</italic>&lt;0.05), depleted GSH level (<italic>p</italic>&lt;0.01), increased activity of GSH-Px (<italic>p</italic>&lt;0.05) and inhibited CAT activity (<italic>p</italic>&lt;0.01) were found in Cd-treated group compared to controls. Manganese(II) pre-treatment either completely prevented (LP, GSH, GSH-Px) or significantly attenuated (CAT) these changes. Manganese(II) treatment alone decreased LP, enhanced hepatic GSH level and had no effect on antioxidant enzymes compared to control group. A significant increase of Cd concentration in the liver and decreased Cd concentration in the kidneys and testes were found in Cd+Mn treated mice compared to Cd-only treated group. The effect of manganese may result from a different metallothionein induction in particular organs. Manganese(II) pretreatment attenuated the interference of cadmium with Ca homeostasis, the alteration in Zn and Cu levels remained mostly unaffected.</p></abstract>ARTICLEtrue electrogastrography in experimental pigs<abstract xml:lang="en"><title style='display:none'>Preclinical electrogastrography in experimental pigs</title><p>Surface electrogastrography (EGG) is a non-invasive means of recording gastric myoelectric activity or slow waves from cutaneous leads placed over the stomach. This paper provides a comprehensive review of preclinical EGG. Our group recently set up and worked out the methods for EGG in experimental pigs. We gained our initial experience in the use of EGG in assessment of porcine gastric myoelectric activity after volume challenge and after intragastric administration of itopride and erythromycin. The mean dominant frequency in pigs is comparable with that found in humans. EGG in experimental pigs is feasible. Experimental EGG is an important basis for further preclinical projects in pharmacology and toxicology.</p></abstract>ARTICLEtrue memory of Prof. Helena Rašková, MD., DSc., Dr.h.c.<abstract xml:lang="en"><title style='display:none'>In memory of Prof. Helena Rašková, MD., DSc., Dr.h.c.</title><p>On April 13, 2010, Prof. Helena Rašková, MD, DrSc., Dr.h.c., the legendary figure of Czecho-Slovak and world pharmacology, passed away. She was born in 1913 in Laussane in a physician's family of a Czech father and Russian mother. She was predestinated for science even due to her childhood experience and meetings with A. Einstein and the later Nobel prize winner W. Hess, who played in a chamber quartet with her father. Moreover, she became a polyglot from the earliest time of her life (Czech from her father, Russian from her mother), Switzerdeutsch and Hochdeutsch from nursary rhymes, French in the elementary school in Zurich and basic English in convent summer school in Weymouth, where as she put it "she got an early lesson that one loves one's own country but is also a citizen of the world".</p></abstract>ARTICLEtrue of pomiferin administration on kidney ischaemia-reperfusion injury in rats<abstract xml:lang="en"><title style='display:none'>Effect of pomiferin administration on kidney ischaemia-reperfusion injury in rats</title><p>The aim of the study was to analyse protective effects of different doses of pomiferin in therapy of reperfusion injury. Rats were randomly divided into five groups (n=10). One group was intact. Three medicated groups and one placebo group were subjected to ischaemia and reperfusion of the left kidney. Pomiferin was administrated by single gastric gavage in 2 ml of 0.5% Avicel solution in doses of 5, 10 and 20 mg/kg. The placebo group was given only Avicel solution. On day 15, all the animals were exsanguinated and the reperfused kidneys were recovered. Selected biochemical markers were assessed in blood: antioxidative enzymes, total antioxidative capacity, malondialdehyde, creatinine, urea and uric acid. Creatinine, urea and total proteins were analysed in urine and 24-hour diuresis was recorded. The kidney tissue samples were used for histopathological examination.</p><p>The results confirmed the expected protective effects of pomiferin. Pomiferin supported defensive reactions of the body against free radicals (increased levels of superoxide dismutase, total antioxidative capacity), decreased lipid peroxidation (decreased malondialdehyde) and contributed to the recovery of kidney functions (creatinine and urea in blood). The best biochemical and histopathological results were achieved after pomiferin administration in the dose of 5 mg/kg.</p></abstract>ARTICLEtrue and histone deacetylases as targets for neuroblastoma treatment<abstract xml:lang="en"><title style='display:none'>DNA and histone deacetylases as targets for neuroblastoma treatment</title><p>Neuroblastoma, a tumor of the peripheral sympathetic nervous system, is the most frequent solid extra cranial tumor in children and is a major cause of death from neoplasia in infancy. Still little improvement in therapeutic options has been made, requiring a need for the development of new therapies. In our laboratory, we address still unsettled questions, which of mechanisms of action of DNA-damaging drugs both currently use for treatment of human neuroblastomas (doxorubicin, cis-platin, cyclophosphamide and etoposide) and another anticancer agent decreasing growth of neuroblastomas <italic>in vitro</italic>, ellipticine, are predominant mechanism(s) responsible for their antitumor action in neuroblastoma cell lines <italic>in vitro.</italic> Because hypoxia frequently occurs in tumors and strongly correlates with advanced disease and poor outcome caused by chemoresistance, the effects of hypoxia on efficiencies and mechanisms of actions of these drugs in neuroblastomas are also investigated. Since the epigenetic structure of DNA and its lesions play a role in the origin of human neuroblastomas, pharmaceutical manipulation of the epigenome may offer other treatment options also for neuroblastomas. Therefore, the effects of histone deacetylase inhibitors on growth of neuroblastoma and combination of these compounds with doxorubicin, cis-platin, etoposide and ellipticine as well as mechanisms of such effects in human neuroblastona cell lines <italic>in vitro</italic> are also investigated. Such a study will increase our knowledge to explain the proper function of these drugs on the molecular level, which should be utilized for the development of new therapies for neuroblastomas.</p></abstract>ARTICLEtrue of perfluorinated carboxylic acids for aquatic organisms<abstract xml:lang="en"><title style='display:none'>Toxicity of perfluorinated carboxylic acids for aquatic organisms</title><p>Toxicity of perfluorinated carboxylic acids with carbon chain C<sub>8</sub> to C<sub>12</sub> were tested with oligochaeta <italic>Tubifex tubifex.</italic> Toxicity was evaluated as the exposure time ET<sub>50</sub> from onset of damage of the oligochaeta in saturated aqueous solutions. The ET<sub>50</sub> fluctuated between 25 and 257 minutes. No statistically significant difference was found among the C<sub>8</sub>, C<sub>9</sub> and C<sub>12</sub> acids (ET<sub>50</sub> between 143 and 257 minutes with large standard deviation). The acids with carbon chain C<sub>10</sub> and C<sub>11</sub> induced the effect significantly quicker (25 to 47 minutes). No acute toxicity measured in the three-minute test was observed in any case.</p></abstract>ARTICLEtrue for Prof. Helena Rašková, MD., DSc., Dr.h.c. 2 January, 1913 †13 April, 2010<abstract xml:lang="en"><title style='display:none'>Obituary for Prof. Helena Rašková, MD., DSc., Dr.h.c. <sup>*</sup>2 January, 1913 †13 April, 2010</title><p>Professor Rašková had been a member, and after her retirement, an honorary member of a number of scientific societies and editorial boards in Slovakia as well as abroad. To provide a list of all decorations and honours given to Professor Rašková would take a lot of space. Of them, let us mention only that she had been decorated with the Finnish Sibelius Medal, the French medal of the of Académie de Lutec, the Gold Medal of European Pharmacological Societies for her contributions to the development of world pharmacology, as well as all the decorations obtained from the Slovak Academy of Sciences: Gold Medal of the Slovak Academy of Sciences, Honourable Gold Medal of the Slovak Academy of Sciences for her contributions to biological sciences, and the Memorable Medal of the Slovak Academy of Sciences. Professor Rašková was an honorary member of the Learned Society of the Slovak Academy of Sciences</p></abstract>ARTICLEtrue manifestations of developmental impairment of the brain<abstract xml:lang="en"><title style='display:none'>Neurobehavioral manifestations of developmental impairment of the brain</title><p>Individual characteristics of human nature (<italic>e.g.</italic> introversion, extroversion, mood, activity, adaptability, aggressiveness, social ability, anxiety) do not need to be primarily innate. They can be determined by the action of various influences and their interactions on functional development of the brain. There is ample epidemiological and experimental evidence that chemical and/or physical factors acting during sensitive time windows of the brain development can cause mental, behavioral, emotional and/or cognitive disorders. Environmental pollutants, addictive substances, drugs, malnutrition, excessive stress and/or hypoxia-ischemia were reported to induce functional maldevelopment of the brain with consequent neurobehavioral disorders. The article provides review on most significant neurobehavioral manifestations of developmental impairment of the brain during prenatal, perinatal and early postnatal period. The most known adverse factors causing developmental neurobehavioral dysfunctions in humans as well as in experimental animals are discussed.</p></abstract>ARTICLEtrue of tramadol dependence on male sexual dysfunction<abstract><title style='display:none'>Abstract</title><p>Tramadol dependence became an increasing and alarming problem in the Egyptian community. Wide availability of tramadol as a pain killer and its role in the treatment of premature ejaculation may be the most apparent causes of increased magnitude of the problem among youth who believe that tramadol has a positive impact on their sexual functions. This study aimed to explore the real impact of chronic tramadol administration on sexual functions in males dependent on tramadol. The study was carried on 80 subjects (50 subjects were tramadol dependent group and 30 subjects represented the control group). Personal, family and past histories were obtained from all the participants in addition to the toxicological history from tramadol dependent group. Urine screening for tramadol was done for all cases of history of tramadol dependence then confirmation by HPLC technique to measure tramadol blood level was done. Both groups were investigated for serum testosterone and prolactin level. Curiosity (22%) and treatment of premature ejaculation (20%) were the main motives for dependence. Erectile dysfunction and decreased libido occurred in 44% and 48% of tramadol dependent group respectively. Significant increase in erectile dysfunction and decreased libido was noted as the duration of dependence increased. Additionally, significant decrease in serum testosterone level and increase in serum prolactin level as tramadol daily dose and duration increased was found. In conclusion, men who take tramadol for premature ejaculation or any other purpose must know that they are very susceptible to many sexual dysfunctions.</p></abstract>ARTICLEtrue and histopathological effects of sub-acute exposure of albino rats to fumigants – dichlorvos and cypermethrin<abstract><title style='display:none'>Abstract</title><p>Cypermethrin (CYP) is one of the most common active ingredients in most insecticides, mosquito coils and powder used in Nigeria. dichlorvos (DDVP) is the most indiscriminately used fumigant in most rural and sub-urban areas in Nigeria. These fumigants can easily be accessed without proper method of usage thus exposing the population to their toxic effects. As a result, this study was initiated to determine the effects of sub-acute exposure of CYP and DDVP on some biochemical and histopathological parameters of albino rats. In this study, forty (40) albino rats of 10 groups of 4 rats per group, with one group serving as control, were exposed to these fumigants in a poorly ventilated area for 4hours per day over 2, 4 and 6 weeks. The results showed observable changes in liver enzyme activities (<italic>p</italic>&lt;0.05) in groups exposed to DDVP for 2, 4 and 6 weeks. The groups exposed to CYP showed mild changes in liver enzyme activities when compared with the DDVP groups. Increase in activity of the liver enzymes was also observed in the groups exposed to a mixture of DDVP+CYP for 2, 4 and 6 weeks. The urea, creatinine and electrolytes levels in all the groups exposed to DDVP, CYP and DDVP+CYP for 2, 4 and 6weeks were significantly (<italic>p</italic>&lt;0.05) increased. Also WBC and platelets in all the groups exposed to DDVP and CYP recorded significant changes. The histology report of the lungs and liver showed moderate lymphocytic infiltration and hepatocytic steatosis which progressed with duration of exposure to the fumigants, while the kidneys showed no remarkable changes. The results of this study suggest that DDVP and CYP have relative toxic effects in the exposed animals and should be used with caution to avoid human exposure to their visible toxicities.</p></abstract>ARTICLEtrue of protection of rat hepatocytes from acetaminophen-induced cellular damage by ethanol extract of<abstract><title style='display:none'>Abstract</title><p>The aim of this study is to evaluate the protective effect of ethanol extract of <italic>Aerva lanata</italic> (EEAL) in preventing acetaminophen induced liver toxicity. EEAL was prepared and its hepatoprotective effect was studied in both isolated primary hepatocytes <italic>in vitro</italic> and in Sprague Dawley rats <italic>in vivo</italic>. For <italic>in vivo</italic> studies, the animals were grouped as Group I – Control; Group II – ACN (2 g/kg b.w.); Group III – EEAL (50 mg/kg b.w.) + ACN (2 g/kg b.w.), Group IV – EEAL (100 mg/kg b.w.) + ACN (2 g/kg b.w.). Extracellular activities of the enzymes liver aminotransferease (GOT, GPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in isolated hepatocytes and rat plasma were studied colorimetrically. Expression of GST, Nrf2, COX 1 &amp; COX2 genes in rat liver were evaluated by RT-PCR. The results showed that ACN induced down-regulation of Nrf2 and upregulation of GST gene expression, which were modulated by EEAL treatment. GOT, GPT, ALP and LDH levels were found to be lowered in both hepatocyte culture media and plasma following EEAL treatment. In addition, the medium GOT and GPT levels were diminished following EEAL treatment only. Moreover, only ALP and LDH in serum appeared to be at normal level following EEAL treatment, whereas GOT and GPT showed levels lower than control. ACN treatment increased the expression of pro-inflammatory COX 1 and COX 2 genes and the levels of these genes were reduced by EEAL treatment. EEAL pre-treated rats exposed to ACN were found to retain normal hepatic structure compared to ACN alone treated rats. From these results it can be concluded that ethanol extract of <italic>A. lanata</italic> possesses both anti-inflammatory and hepatoprotective activity.</p></abstract>ARTICLEtrue migration measurement through spectrophotometry device and the effect of time and tableware type on it<abstract><title style='display:none'>Abstract</title><p>Melamine is an organic-based chemical material widely used in the production of tableware. Given the adverse effects of melamine on human health, melamine tableware can be a source for its introduction into the human body. The aim of this study was to use a simple method for monitoring the rate of melamine migration from the tableware to food and the effect of time and tableware on this migration. To measure the migration, spectrophotometry was used. The limit of detection (LOD) of the method was 0.2 (μg/ml), which is functional for measuring the rate of migration. The investigation of sample migration of melamine tableware revealed that migration has occurred across all samples. The rate of migration in all samples was less than the standard level of the European Union (30 μg/ml). Statistical analysis indicated that time is an important factor in melamine migration, which significantly increased (<italic>p</italic>&lt;0.05) in 93% of cases with lengthening the contact time from 30 minutes to 90 minutes. The type of tableware (new or old) and production conditions (standard or non-standard) were found to significantly affect (<italic>p</italic>&lt;0.001) the rate of migration. Statistical analysis of the results suggested that old tableware increased melamine migration in 41% of cases (<italic>p</italic>&lt;0.05). Non-standard tableware significantly (<italic>p</italic>&lt;0.001) increased the rate of migration and thus the effect of non-standard production on melamine tableware was more significant than the age of the tableware.</p></abstract>ARTICLEtrue effect of venlafaxine on blood pressure and ECG in rats fed with high-fat-fructose diet<abstract><title style='display:none'>Abstract</title><p>Metabolic syndrome represents one of the major health, social and economic issues nowadays, and affects more than 25% people worldwide. Being a multifactorial health problem, metabolic syndrome clusters various features, such as obesity, dyslipidemia, hyperglycemia and hypertension. Each of these disturbances represents a risk factor for developing cardiovascular disease. Moreover, patients with metabolic syndrome are more likely to suffer from depression, thus treatment with antidepressants (<italic>e.g.</italic> venlafaxine) is often neccessary. However, many of the antidepressants themselves may contribute to worsening or even development of the metabolic syndrome, thus creating a “vicious circle”. The aim of this work was to investigate on the animal model of metabolic syndrome, i.e. on hypertriacylglycerolemic rats fed high-fat-fructose diet (HFFD): 1) the effect of a change in diet from HFFD to a standard diet (SD) and the effect of venlafaxine treatment, 2) during HFFD, 3) as well as during a changed diet to SD. We focused on biometric parameters, blood pressure and selected ECG parameters. We observed the reversibility of the present metabolic and cardiovascular changes by switching the HFFD to SD in the last 3 weeks of the experiment. Switch to the standard diet led to decrease of body weight, even in the presence of venlafaxine. Administration of venlafaxine caused the decrease of heart weight/body weight index in rats fed with HFFD compared to the untreated group fed with HFFD for 8 weeks. Blood pressure, which was increased in the HFFD group showed a tendency to decrease to control values after switching to the standard diet. Administration of venlafaxine led to significant increase in all parameters of blood pressure when rats were fed with HFFD throughout the whole experiment. In untreated rats fed with HFFD for 8 weeks, we observed a shorter PQ interval and prolonged QRS complex as well as QTc interval compared to untreated rats with diet switched to SD. This effect was potentiated by venlafaxine administered not only during HFFD but even after switch to SD. Our results point to the fact that metabolic syndrome is clearly affecting the function of the cardiovascular system by modifying blood pressure and electrical activity of the heart. Moreover, administration of venlafaxine may lead to worsening of the observed changes, especially in the presence of high-fat-fructose diet.</p></abstract>ARTICLEtrue hepatoprotective and antioxidative effect of saffron stigma alcoholic extract against vincristine sulfate induced toxicity in rats<abstract><title style='display:none'>Abstract</title><p>Vincristine (VCR) is an important anti-cancer drug, which is highly toxic for the liver. This study aimed at evaluating the protective effect of alcoholic extract of saffron stigma against vincristine hepatotoxicity in the rat. A total number of 50 rats were randomly divided into 10 groups, including controls, rats receiving 0.25 mg/kg (A group), 0.5 mg/kg (B group), 0.75 mg/kg (C group) VCR, 0.25 mg/kg VCR + 0.5 mg/kg saffron (D group), 0.5 mg/kg VCR + 0.5 mg/kg saffron (E group), 0.75 mg/kg VCR + 0.5 mg/kg saffron (F group), 0.25 mg/kg VCR + 1mg/kg saffron (G group), 0.5 mg/kg VCR + 1 mg/kg saffron (H group), and 0.75 mg/kg VCR + 1 mg/kg saffron (I group) groups. Serum level of liver enzymes, including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and bilirubin were measured using specific kits at the end of the experimental period. Serum total antioxidant capacity (TAC) and malondialdehyde (MDA) values were measured using ferric reducing antioxidant of power (FRAP) and thiobarbituric acid reaction (TBAR) methods, respectively. Administration of VCR, especially at the concentration of 0.75mg/kg, caused severe hepatic injury with significant increase in the levels of AST (582.0±39.45 UI), ALT (124.0±5.92 UI), ALP (939.8±89.8 UI) enzymes and bilirubin (0.17±0.008). VCR administration also significantly increased the serum MDA level (0.49±0.021 nmol/ml), while TAC value was declined significantly (241.27±18.27 μmol/l). These effects were dose-dependent. Treatment with saffron extract decreased the activity of liver enzymes and MDA values in hepatotoxic rats with a significant enhancement in serum TAC content. These effects were notable for rats that received 1mg/kg plant extract. Administration of saffron, especially at higher concentration, can reduce VCR-induced hepatotoxicity, antioxidant depletion and lipid peroxidation, presumably due to its antioxidative properties.</p></abstract>ARTICLEtrue present approaches to the development of prophylactic and therapeutic antidotes against nerve agents<abstract xml:lang="en"><title style='display:none'>The present approaches to the development of prophylactic and therapeutic antidotes against nerve agents</title><p>Nerve agents belong to highly toxic organophosphorus compounds misused as chemical warfare agents for military as well as terroristic purposes. Basic mechanism of action of nerve agents is based on acetylcholinesterase (AChE, EC inhibition and subsequent accumulation of neuromediator acetylcholine at the cholinergic synapses, either peripheral or central leading to cholinergic hyperstimulation and development of symptoms of poisoning, followed by metabolic dysbalance and death without effective prophylaxis/treatment. The antidotal treatment of acute poisonings with nerve agents still represents a serious problem and, therefore, we are searching how to satisfactorily protect people against acute toxicity of nerve agents. There are two approaches how to improve the medical protection against nerve agents:</p><p>to increase the resistance of nerve agent-exposed organism and the efficacy of post-exposure antidotal treatment by pharmacological prophylaxis</p><p>the development of new, more effective antidotes, expecially AChE reactivators, to achieve the satisfactorily effective antidotal treatment of acute poisonings with nerve agents.</p></abstract>ARTICLEtrue in the study of genetic susceptibility<abstract xml:lang="en"><title style='display:none'>Trends in the study of genetic susceptibility</title><p>Genotoxicology investigates the molecular basis of cellular responses to DNA damage. During more than three decades of genetic toxicology testing, a large number of tests with varying sensitivity and specificity have been developed.</p><p>These genotoxicity tests can predict:</p><p>the likelihood of a substance to be a (rodent) carcinogen,</p><p>the mechanism of carcinogenic activity of different substances,</p><p>if the results of genotoxicity studies only predict carcinogenicity or they are a distinct hazard endpoint (Nohynek, 2005).</p><p>The current genetic toxicity testing batteries represent:</p><p>Ames test which is a component of all genetic testing batteries.</p><p>A mammalian cell mutagenicity assay which should confirm or complete the Ames test.</p><p>Chromosomal aberrations tests which are based on a different endpoint than gene mutations.</p><p>Positive <italic>in vitro</italic> results need to be confirmed by in vivo tests; results from test batteries have higher predictive value than results of a single test (Nohynek, 2005).</p></abstract>ARTICLEtrue systems of detoxication — overview of recent approaches<abstract xml:lang="en"><title style='display:none'>Enzyme systems of detoxication — overview of recent approaches</title><p>The most important enzymes of detoxication are cytochromes P450 of Phase I and UDPglucuronosyltransferases of Phase II of drug metabolism. The conventional division of drug, or xenobiotic, metabolism to two phases has survived almost fifty years and although not perfect, still is rather informative and practical. The recent addition of the next, third phase to the first two (Phase I as yielding a molecule with free functional groups ready for conjugation with another molecule or its part in Phase II) stressed the importance of drug transport across the membranes even if it is not a pure metabolic process (i.e. a process changing the polarity and structure of a compound).</p></abstract>ARTICLEtrue issues in developmental toxicity testing<abstract xml:lang="en"><title style='display:none'>Important issues in developmental toxicity testing</title><p>Studies of individual development and its possible deterioration have been the concern since the 19th century, when Etienne Geoffroy de Saint-Hilaire (1772-1844) with his pioneer experiments opened the door for future experimental teratologists. Later scientists, focused on environmental agents which can alter embryonic and fetal development, such hyperthermia, malnutrition, pharmaceuticals, microbial toxins etc. Although the history of teratology involves many notable scientists, it has gained prominence after the big thalidomide tragedy in 1961. Principles of teratology were proposed later by James Wilson in his monograph <italic>Environment and Birth Defects</italic> (Wilson, 1973).</p></abstract>ARTICLEtrue