General Toxic Effects Research Articles

The glyphosate influence on cytogenetic and biochemical aspects of wheat (Triticum aestivum L) seedlings development

The influence of glyphosate on the germination and development of bread wheat (Triticum aestivum) was researched. The chronical influence during all the time of growth was estimated, together with the consequences of the contact with glyphosate of the already formed seedlings. A dose-dependent decrease in the growth rate of seedlings in the presence of glyphosate was found, and even in normally developing seedlings damage to the root tips was observed. In particular, in seedlings, the integrity of the root cap was disrupted, degenerative changes of the rhizodermis and root hairs were detected. It has been shown that a decrease in the root growth rate during chronic exposure is largely due to the suppression of mitoses. In addition, high glyphosate concentrations had a general toxic effect, stopping the development of seedlings yet at the stage of primary roots growth through enlarging the cells. It was found that the antioxidant system of seedlings prevented the development of oxidative stress at the concentration of herbicide 50 μM, in particular, due to the activation of peroxidase. Placing seedlings grown on distilled water in 100 μM glyphosate solution induced lipid peroxidation. Chronic effects of herbicide in this concentration inhibited lipid metabolism in general.

Methods of assessing the health impacts of chemicals ingested with drinking water

Assessment of non-carcinogenic and carcinogenic risks of per oral intake of chemicals with drinking water for children aged 3-6 year sold living in 4 districts (zones) of the city of Kazan was carried out. A quantitative characteristic of risk was performed with application of regional exposure factors (REF) at the median level (Me) and the 95-thpercentile (95P). Analysis of the risk data showed that only 5 substances (magnesium, nitrates (in NO3), fluorides, oil products, and chloroform) made from 62.5% to 89.8% of contribution to total risk value in all zones. General toxic effects for critical organs and systems were due to oil products (from 29 to 54.7%) in the 2nd and the 4th zones, chloroform (from 10 to 30.6%) and nitrates (from 12.8 to 35.9%) in all zones, magnesium (up to 11.2%) in the 3rd zone, and fluorides (from 13.7 to 14.3%) in the 1st and the 3rd zones. The unacceptable risk level (HIMe = 11.8 and 9.9; HI95-th Perc = 14.8 and 12.5) was identified in the 2nd and the 4th zones with a mixed type of water in the utility and drinking water supply. The ingestion of chemicals with drinking water in different zones of the city of Kazan indicates an alarming and high level of non-carcinogenic and carcinogenic risks for the child population health.

A protective role of autophagy in Pb-induced developmental neurotoxicity in zebrafish

Lead (Pb) is one of the most toxic heavy metals and has aroused widespread concern as it can cause severe impairments in the developing nervous system. Autophagy has been proposed as an injury factor in Pb-induced neurotoxicity. In this study, we used zebrafish embryo as a model, measured the general toxic effects of Pb, and investigated the effect of Pb exposure on autophagy, and its role in Pb-induced developmental neurotoxicity. Zebrafish embryos were exposed to Pb at concentrations of 0, 0.1, 1 or 10 μM until 4 days post-fertilization. Our data showed that exposure to 10 μM Pb significantly reduced survival rates and impaired locomotor activity. Uptake of Pb was enhanced as the concentration and duration of exposure increased. Inhibition of lysosomal degradation with bafilomycin A1 treatment abolished the suppression of Lc3-II protein expression by Pb. Furthermore, autophagosome formation was inhibited by Pb in the brain. In addition, mRNA expression of beclin1, one of the critical genes in autophagy, were decreased in Pb exposure groups at 72 h post-fertilization. Whole-mount in situ hybridization assay showed that beclin1 gene expression in the brain was reduced by Pb. Rapamycin, an autophagy inducer, partly resolved developmental neurotoxicity induced by Pb exposure. Our results suggest that autophagy plays a protective role in the developmental neurotoxicity of Pb in zebrafish embryos and larvae.

ACUTE TOXICITY OF CERIUM DIOXIDE NANOPARTICLES

The resorptive effects of 0.01 M cerium nanodioxide sol upon single intraperitoneal administration to rats have been studied. The acute exposure to nanoparticles was found to have a dose-dependent general toxic effect on the body (weight loss, inflammatory changes in the abdominal organs, modification of individual behavior, hematological changes, metabolic imbalance), which develops on the background of POL activation. The prooxidant effect of cerium dioxide nanoparticles is demonstratively manifested at relatively high exposure levels (80–8 mg / kg). The threshold dose for the general toxic effect (Limch integr) is equal to 0.8 mg / kg.

POISONOUS SNAKES OF BULGARIA: СLINICAL AND EPIDEMIOLOGICAL ANALYSIS

Snakes are cold-blooded, legless reptiles of the suborder Serpentes. They belong to the order - Squamates. They conjure contradictory feelings in man: fear and honor, disgust and admiration. Snake symbol is found in almost all cultures of the world. Snake is perceived variously by different nations and different religions. In one, the snake is a symbol of the environmental forces of nature, and in others it is associated with evil and chaos. Of the 3000 species of snakes in the globe, only 400 are poisonous. The aim of the present study is to analyze the clinical course, the specific treatment and the prophylactic measures for poisonous snakes bites, the presentation of the poisonous snakes in Bulgaria and the most poisonous ones in the world. Analysis of epidemiological data in the world and in the Pleven region for the last 8 years. This study investigates clinical cases of poisonous bites in the Pleven region. Was obtained a comparative analysis of epidemiological data and methodological justification of the results. There are 18 species of snakes in Bulgaria, 4 of which are poisonous. Snakes that may pose a threat to human life are Vipera berus and the Vipera ammodytes. Definitive for snake bite is a combination of local toxic damages with general toxic effects. The bites of the Vipera berus are leading in Pleven region because of geographical peculiarities (altitude). For the period 2011 – 2018 years 63 patients with snakes bites were hospitalized. They account 1.75% of the total toxicology pathology. 52% of them are men and 48% are women. 56 % of patients were only with local symptoms, 44% were with local and general symptoms. 69% of patients were with slightly severity of the clinical course, 23% were with medium severity and 8% with high severity. Lethal cases were 0%. According to WHO data, 5 million people are exposed to bites per year. Prior to applying modern treatment methods, lethality accounts for 20-40% and in some countries up to 70%. Now, thanks to the use of anti-virus serum, the number of deaths has decreased significantly. Although there are no lethal snakes in Bulgaria, every bite is not to be underestimated due to the fact that complications for people with health problems are very severe.

Immuno-toxicological Evaluation of the Adjuvant Formulations for Experimental Anti-meningococcal Vaccines without Aluminium Hydroxide

The proteoliposomes and cochleates are used as adjuvants for vaccines since they are potent immune stimulators. However, the hyper stimulation of the immune system provoked by adjuvants can cause immune-toxicological side effects. The present study was carried out to evaluate the toxic and immuno-toxicological effects of new adjuvants for anti-meningococci vaccines based on neo-proteoliposomes (nPL) and neo-cochleates (nCh), in Balb/c mice that were administered doses of 15 �g each, over periods of 14 days through intramuscular route and three inoculations with the same doses through intranasal route, every 7 days. The Scanning and Transmission Electron Microscopy showed that the nPL and nCh had nanometric dimensions and their normal peculiar forms. The experimental formulations did not provoke general toxic effects in the tested animals, which tended to the progressive normal growing of this species, that did not statistically differ from the control ones. The studies of pathologic anatomy in inoculation organs and sites did not reveal modifications that can indicate toxicity and there was no sign of hepatic damage. The structural observations found in the spleen and lymphatic nodes showed the physiological development of the immune response, which was normal in all cases showing the restitution of the stimulation signs. The relative weight values of the spleen were within the standard range. These results showed that the nPL and nCh elaborated as adjuvants for vaccines did not show any evident induction of general toxic or particular immune-toxicologicl effects.

AIR POLLUTION RISK TO HEALTH OF THE POPULATION OF THE CITIES SAMARA AND NOVOKUIBYSHEVSK

There are presented results of the analysis of a risk to public health of cities of Samara and Novokuibyshevsk. We assessed the content of harmful substances in the air at fixed stations located within the city boundaries on a well-ventilated area. The risk to health is calculated in accordance with the R 2.1.10.1920-04. During the period 2014-2015 we fixed the impurity concentration in excess of the average daily maximal permissible concentrations of carcinogens of the first and second classes of danger (benzo[a]pyrene and formaldehyde), as well as ammonia, which has a general toxic effect. The average concentration of phenol and formaldehyde within the territory of the city of Novokuibyshevsk were in the range of the average daily maximal permissible concentrations. Within the city of Samara in the air annual average concentrations of formaldehyde, only slightly exceeding the daily maximal permissible concentrations value of 1.39 in 2015 were registered. The total cancer risk to public health in the city of Samara as a whole for the period 2014-2015 amounted to 2.77·10-4, the total hazard index - 18.35. For the health of the population of the city of Novokuibyshevsk the level of total cancer risk is equal to 1.37·10-4, the total hazard index - 14.64. Hexavalent chromium, formaldehyde and benzene seem to be main pollutants that form the total level of carcinogenic risk to public health in the cities of Samara and Novokuibyshevsk. Copper (I place ranking), contained in large quantities in the emissions of non-ferrous metallurgy is the priority chemical, forming the total index of the risk of developing non-carcinogenic effects in the population of the city of Samara and Novokuibyshevsk. Petrochemicals are related with the values of the total cancer risk and total hazard index unacceptable for public health in cities of Samara and Novokuibyshevsk and require planned measures aimed at improving the environment in the near future.

COMPARATIVE CHARACTERISTICS OF THE CRYSTALLOGRAM OF THE ORAL FLUID IN PATIENTS WHO USE HEROIN AND METHADONE

Currently, the problem of drug addiction is one of the main not only in healthcare but also in society, because it poses a serious threat to the life and health of the working-age population. Persons suffering from drug addiction, are characterized not only by severe disorders of the Central nervous system, internal organs, but also pathological changes in the mucous membrane of the oral cavity. The results of studies indicate that persons suffering from drug dependence on opiates (mainly from heroin addiction) and taking methadone (a synthetic drug from the group of opioids used in some countries as substitution therapy in the treatment of drug dependence), along with the general toxic effects on the body, there are significant changes in the state of the dentition.The aim of the work is to analyze the results of oral fluid crystallograms in patients using heroin and methadone and to identify the features of crystal morphology depending on the substance used. For the first time, changes in crystal morphology were detected in patients taking heroin and methadone. The article presents the results of the analysis of crystallograms of oral fluid of patients using heroin and methadone, the features of their morphology, distinctive quality features, including the lack of crystal growth and rupture of its structure. It is noted that these morphological changes in the crystallization of oral fluid of drug-dependent patients identified for the first time and can be used for diagnostic purposes in dentistry to identify patients who use heroin or methadone. Analysis of the results of these crystallograms in the studied categories of patients allows to differentiate them depending on the substance used (heroin, methadone), which can be used in clinical practice.

Study of gonado- and reproductive toxicity of technical-grade carbendazim in male and female Wistar Han rats

Objective. Identification of hazard and assessment of the risk of gonado- and reproductive toxicity of two generic pesticides of technical-grade carbendazim of different purity bin male and female Wistar Han rats. Materials and Methods. Carbendazim with the purity of 98 % (C1) and 98.1 % (C2) was intragastrically administered on the daily basis, excluding Saturday and Sunday, at the doses of 2.5 and 25 mg/kg body weight in three groups of animals (20 males and female rats in each) during 10 weeks (forfemales) and 11 weeks (for males). Control animals received an equivalent amount of the solvent. Intact animals intended for breeding were managed in parallel with the control and experimental animals. After the end of the exposure, functional parameters of the condition of gonads and reproductive ability of the animals were investigated. Females were used to investigate the condition of the oestral cycle, duration and frequency of each stage of it. The condition of the reproductive function in the female rats was considered at Day 20 of pregnancy. Indices of breeding, conception, fertility, pregnancy were established, and the duration of the pre-coitalperiod was considered. Results and Discussion. The data obtained suggest that exposure to two generic substances of carbendazim at the dose of 25 mg/kg body weight during 11 weeks is manifested in general toxic effect (body weight reduction) only in males upon exposure to C2. All test substances in the maximum dose have reproductive toxicity and show significant anti-androgenic action that is manifested as changes in the morphological and functional parameters of the condition of gonads in the experimental groups of male rats. Furthermore, the negative effect on the oestral cycle in experimental female rats exposed to C2 was noted. Conclusion. Based on the obtained results it can be concluded that all test samples of carbendazim have reproductive toxicity at the dose of 25 mg/kg body weight. No-observed-effect level (NOEL) for all test compounds is 2.5 mg/kg body weight. Dose-effect dependence was observed in the range of studies doses.

Effects of norfloxacin exposure on neurodevelopment of zebrafish (Danio rerio) embryos

In view of the wide application of fluoroquinolones (FQs), a group of broad-spectrum synthetic antibacterial agents, and their large ingress into the environment, the toxic effects on non-target organisms caused by FQs have received great attention. In this study, we used zebrafish embryo as a model, measured the general toxic effects of norfloxacin, a commonly used FQs, and investigated the effects of norfloxacin on the neurodevelopment of zebrafish embryos. Our data showed that norfloxacin significantly inhibited the hatching rate of zebrafish embryos, and increased the mortality and malformation rate of the embryos. To discuss the developmental neurotoxicity of norfloxacin, we measured the expression of several stem cell and neuron lineage markers in the zebrafish embryos. We found that norfloxacin exposure inhibited the expression of GFAP (glial cell marker), and enhanced the expression of Sox 2 (stem cell marker) and Eno2 (mature neuron marker). By measuring the level of active Caspase 3 and the expression ratio of Bax to Bcl2, we discovered that norfloxacin induced obvious cell apoptosis in the brain of zebrafish embryos. To explore the mechanism of the developmental neurotoxic effects of norfloxacin, we applied MK-801, a non-competitive NMDA receptors antagonist, to block the actions of NMDA receptors. The results indicated that MK-801 could rescue the upregulated cell apoptosis and disrupted balance of neuro-glial differentiation induced by norfloxacin in the brain of zebrafish embryos. Our results suggest that the activation of NMDA receptors mediates the developmental neurotoxicity of norfloxacin.

СОВРЕМЕННЫЕ ТРЕБОВАНИЯ К ИЗУЧЕНИЮ ОБЩЕТОКСИЧЕСКОГО ДЕЙСТВИЯ ФАРМАКОЛОГИЧЕСКИХ ВЕЩЕСТВ

The article provides an overview of methodical recommendations, rules and guidelines for conducting preclinical studies of general toxic effect of pharmacological substances on the basis of international requirements for research. The introduction of new drugs for veterinary use into civil circulation is preceded by set of scientific studies to assess their effectiveness and safety in accordance with modern requirements. At the same time, it is necessary to observe a certain order of research at various levels on the basis of international standards, the most important stage of which is the study of the toxic effect of pharmacological substance in preclinical conditions. Preclinical toxicological studies are carried out in order to exclude in animals of target species possible adverse effects of the drug in the course of clinical trials and their subsequent use in veterinary practice.

Effect of Taurine on Alterations in Deiodinase 3 Expression Induced by BDE 209 in Human Neuroblasoma-Derived SK-N-AS Cells.

PBDEs (stands for polybrominated diphenyl ethers) are extensively utilized flame retardants, and BDE 209 is one of the most widely used congeners. Studies have suggested the general toxic effects of PBDEs on the endocrine system and neural development. Our previous studies found that BDE 209 changed Type 3 iodothyronine deiodinase (Dio 3) expression in human SK-N-AS neuroblastoma cells. The current study was designed to examine the potential protection of taurine on alterations of Dio 3 expression induced by BDE 209 in SK-N-AS cells. Briefly, SK-N-AS cells were pretreated with taurine prior to the BDE 209 treatment, and the cell viability was evaluated by the MTT (methyl-thiazolyl-tetrazolium) assay. The disturbance or restoration in the levels of Dio 3 proteins and mRNA were observed separately by the western blot and qRT-PCR. Our data showed that taurine moderately attenuated BDE 209-mediated the loss of cell viability. Also, taurine moderately prevented the reduction in the Dio 3 protein expression and mRNA expression induced by BDE 209 in the SK-N-AS cells. Our findings indicated that taurine potentially provide the protection on PBDEs-induced toxicity on endocrine and neuro-development.

Generation and characterization of novel recombinant anti-hERG1 scFv antibodies for cancer molecular imaging.

Modern molecular imaging techniques have greatly improved tumor detection and post-treatment follow-up of cancer patients. In this context, antibody-based imaging is rapidly becoming the gold standard, since it combines the unique specificity of antibodies with the sensitivity of the different imaging technologies. The aim of this study was to generate and characterize antibodies in single chain Fragment variable (scFv) format directed to an emerging cancer biomarker, the human ether-à-go-go-related gene-1 (hERG1) potassium channel, and to obtain a proof of concept for their potential use for in vivo molecular imaging.The anti-hERG1scFv was generated from a full length monoclonal antibody and then mutagenized, substituting a Phenylalanine residue in the third framework of the VH domain with a Cysteine residue. The resulting scFv-hERG1-Cys showed much higher stability and protein yield, increased affinity and more advantageous binding kinetics, compared to the “native” anti-hERG1scFv. The scFv-hERG1-Cys was hence chosen and characterized: it showed a good binding to the native hERG1 antigen expressed on cells, was stable in serum and displayed a fast pharmacokinetic profile once injected intravenously in nude mice. The calculated half-life was 3.1 hours and no general toxicity or cardiac toxic effects were detected. Finally, the in vivo distribution of an Alexa Fluor 750 conjugated scFv-hERG1-Cys was evaluated both in healthy and tumor-bearing nude mice, showing a good tumor-to-organ ratio, ideal for visualizing hERG1-expressing tumor masses in vivo.In conclusion, the scFv-hERG1-Cys possesses features which make it a suitable tool for application in cancer molecular imaging.

Дослідження впливу чотирьох генеричних пестицидів лямбда-цигалотрину на репродуктивну функцію самців щурів wistar han

Introduction. Objective is to identify hazard and asses reproductive toxicity risk of four generic lambda-cyhalothrin pesticides of different purity on male Wistar Han rats. Methods. Lambda-cyhalothrin (LC1 — 97 %, LC2 — 96 %, LC3 — 97,1 %, LC4 — 96,7 % purity) was administered intragastrically on a daily basis, exceptfor Saturday and Sunday, at doses of 0,0; 0,3 and 3,0 mg/kg body weight for three groups of animals, 20 males in each, for 11 weeks. Control animals received an equivalent amount of solvent. In parallel with control and experimental animals, there were intact females, intended for mating. At the end of inoculation, functional parameters of the state of gonads and the ability of animals to reproduce offspring were studied. The state of reproductive function in intact females was taken into account at day 20 of pregnancy. Results and discussion. The obtained data indicate that the exposure to four generic lambda-cyhalothrin substances at a dose of 3,0 mg/kg body weight for 11 weeks showed a general toxic effect (weight loss) in males under the effect of LC1. All four test substances have a reproductive toxicity at the maximum dose and have a pronounced antiandrogenic effect, which is manifested in changes in the morphological and functional parameters of the state of the gonads in the experimental groups of males. In addition, there was a negative effect on the fertility of males (LC2), which was concluded by the fertility index in intact females. Conclusion. Based on the results obtained, it can be concluded that all studied lambda-cyhalothrin samples have reproductive toxicity at a dose of 3,0 mg/kg body weight. No observed effect level (NOEL) for all studies substances is the dose of 0,3 mg/kg body weight. In the range of studied doses, there is a dose-effect dependence. Key words: pesticides, cyhalothrin, lambda-cyhalothrin, gonadotoxicity, reproductive toxicity.

Clinical and Morphological Aspects in Assessing the Safety of OSPL-502 with Repeated Dose Administration.

BACKGROUND:OSPL-502 is a new potential medicinal drug which stimulates a cognitive function. It is necessary to reveal clinical manifestations of its general toxic effect and determine organs that are most heavily affected by this pharmacological substance.AIMS:To describe and estimate clinical and histopathological changes in the organism of experimental animals in response to the repeated administration of pharmacological substance OSPL-502.MATERIAL AND METHODS:The study was conducted by the OECD Guidelines (Test No. 407) on Sprague-Dawley rats. The drug was administered at the dose of 20, 60 and 180 mg/kg.RESULTS:The repeated doses of OSPL-502 have not caused any toxic effects on the growth of body weight, food and water consumption of the tested animals, or affected the musculoskeletal system and exploratory behaviour of the rats in the doses of 20 and 60 mg/kg. The dose of 180 mg/kg (1800 times larger than the therapeutic dose) has shown clinical signs of toxicity in females but has not resulted in the death of the animals. Due to morphological methods, we have found histostructural changes in the liver, kidneys and adrenal glands of the rats that were treated with the test substance in the maximum dose. These changes are reversible and reduce within 14 days after the admission of the studied substances is cancelled.CONCLUSION:OSPL-502 at the dose of 180 mg/kg has a weakly pronounced toxic effect, the dose of 60 mg/kg is the threshold, and that of 20 mg/kg is no-observable-adverse-effect-level (NOAEL); the liver, kidneys and adrenal glands can be considered target-organs for the tested substance.

ETYMOLOGICAL PECULIARITIES OF MODERN ACUTE RESPIRATORY VIRAL INFECTIONS IN CHILDREN OF EARLY AGE HOSPITALIZED TO THE INTENSIVE CARE UNIT

Objective: to estimate the prevalence and clinical-epidemiological features of acute respiratory infections of various etiology in children of the first three years of life, hospitalized to the intensive care unit of a children’sinfectious hospital.150 children of the first three years of life of the total number of patients, hospitalized to the intensive care unit of the Republican Clinical Infectious Diseases Hospital of Kazan with a severe ARI, were randomly selected. The design of the research was consistent with the observational analytic.Results: the etiology of ARI was interpreted in 74% (95% CI 67–81), 111/150 cases. Rhinovirus infection is the main cause of development of severe forms of ARI in young children; in second place – influenza viruses – 13.9-28.7% in different age groups. Clinically significant in all age groups were respiratory syncitial viruses (7.1–16.7%), in children up to one year – parainfluenza viruses (13.9% (95% CI 6–21.8), 10/72, and in patients older than 2 years – adenoviruses (12–14.2%). Seasonal rise in the incidence of ARI was noted in the cold season. It was caused by influenza viruses, respiratory syncitial viruses, parainfluenza viruses. In the summer months, the rhino-, metapneumo- and adenoviruses were most common. The expressed general toxic effects that caused hospitalization were recorded in 66% (95% CI 58.4–73.6), 99/150 of the examined patients, manifestations of respiratory failure was detected in 58% (95% CI 50.1–65.9), 87/150.Conclusions: the leading causes of development of severe forms of ARI in young children are rhinoviruses, influenza viruses and the respiratory syncitial virus. They are associated with: respiratory tract diseases with respiratory failure, a symptom complex of toxicosis. Previously thought «harmless», rhinovirus infection is becoming a leader in the range of causes of severe forms of respiratory infections in young children.

Study of PEG-Filstim sub-acute toxicity

Febrile neutropenia caused by cytostatic therapy in the treatment of oncological diseases is a frequent complication, which results in enforced reduction in chemotherapy doses and lower effectiveness of the treatment. Introduction of the recombinant forms of the natural protein granulocyte colony-stimulating factor into clinical practice has allowed to minimize the negative consequences of myelosuppressive therapies. The main task of repeated dose toxicity studies of drugs is evaluation of damaging effects of the pharmacological substance, revealing the most sensitive organs and systems in the body.
 Therefore, our work was aimed at studying sub-acute toxicity of PEG-Filstim.
 Toxicity study of PEG-Filstim was performed in 50 white wild-type rats of both sexes with body weight 170 to 230 g on daily (28 days) subcutaneous administration in the doses of 0.5, 1.0 and 2.0 mg/kg. During the whole observational period, survival, water and food consumption, body weight and symptoms of intoxication were registered. After completion of the experiment, spontaneous diurnal diuresis was evaluated and clinical blood and urine examination performed in all groups of animals.
 The results have shown that PEG-Filstim on daily subcutaneous administration in the doses of 0.5, 1.0 and 2.0 mg/kg during 28 days does not cause death in the animals, nor general toxic effects on health, behaviour, food and water consumption, body weight growth in laboratory rats. Upon repeated administration in the studied doses, PEG-Filstim does not affect protein, lipid, carbohydrate metabolism, does not impair functions of urinary and hepatobiliary systems, but increases blood serum alkaline phosphatase activity. PEG-Filstim causes development of pronounced neutrophil leucocytosis and increase in monocyte, lymphocyte and eosinophil count. In the maximum dose of 2.0 mg/kg the studied drug decreases blood red cell count and haemoglobin level.

Subacute Toxicity Effect of Psidium guajava Leaves Ethanolic Extract on Gaster in Wistar Rat

Psidium guajava leaves have been proven be antiallergic. From the results of previous research, the ethanol extract of leaves is included in the class materials "Practically Non-Toxic." However, repeated administration may cause toxic effects on body organs, one of which was gaster. Subchronic toxicity had been carried out on 20 male Wistar rats and 20 female wistar albino rats. The test materials were administered orally, every day for 28 days. There are 3 (three) doses of test materials which were 250 mg, 500 mg, and 750 mg/kg BW. Observation of the general toxic effect was performed everyday, then organ sampling was performed on day 29 to examined gaster histology and score using Barthel-Manja methods. The result showed that administration of Psidium guajava leaves extract for 28 days caused physical and behavioral changes, caused soft and mucous feces, and also respiratory disorder. But the extract at dose 250 mg, 500 mg and 750 mg/kg BW did not caused changes on gaster histology profile and score. In conclusion, the extract did not have subchronic toxicity effect on gaster rat, but might caused general toxic effect in the higher dose.

Comparative assessment of the effect of course doses of vancomycin + gentamycin and vancomycin + amikacin on immature hearing analyzer

The objective of the work is the comparative study of acoustic function of immature animals after subsequent injection of therapeutic doses of vancomycin and gentamycin (group 1) and vancomycin and amikacin (group 2). The general toxic effect was observed in the first group of animals. More expressed ototoxic effect, according to ABR and DPOAE, was observed in the second group of animals which manifested itself in a more significant rise of ABR 1st peak thresholds. The comparison of the central conduction time did not reveal any significant differences. The injection of vancomycin and gentamycin has resulted in the reduction of DPOAE evoked response at the frequencies of 4 kHz, and the injection of vancomycin and amikacin provided such reduction at the frequency of 6 kHz.

Safety assessment of a standardized cucumber extract (Q-Actin™): Oral repeat-dose toxicity and mutagenicity studies.

Cucumus sativus (cucumber) is one of the most widely consumed fruit vegetables worldwide. Recent discovery of iminosugars in commonly consumed fruits and vegetables has promoted the interest in isolating these compounds and understanding the potential benefits to human health. The objective of the present study was to investigate the general toxicity and mutagenic effects of an aqueous extract of cucumber (Q-Actin), standardized to ≥1% (1–2%) ido-BR1 iminosugar. Single dose of Q-Actin was well tolerated without mortality at 2000 mg/kg body weight (bw) in Sprague Dawley rats. Oral (gavage) administration of Q-Actin up to 1000 mg/kg bw/day was well tolerated followed by repeated administration for a maximum period of 90 days in Sprague-Dawley rats. There were no treatment related changes in clinical observations, ophthalmic examinations, body weights and body weight gains or feed consumption, clinical chemistry and pathological changes compared to control. The mutagenicity as evaluated by Ames assay, in vitro chromosomal aberration test and in vivo micronucleus assay did not reveal any potential of Q-Actin to induce genotoxicity. The results showed that Q-Actin is well tolerated in general toxicity studies and did not induce mutagenicity. The no-observed-adverse-effect level (NOAEL) of the standardized aqueous cucumber extract (Q-Actin) is considered to be ≥1000 mg/kg bw/day, followed by repeated administration for90 days.