FETAL TOXICITY OF HYDROALCOHOLIC EXTRACT OF AGERATUM CONYZOIDES L. LEAVES (ASTERACEAE) IN RATS

Objective: Ageratum conyzoides is known to possess pharmacological and therapeutic pro perties in Africa. Some pyrrolizidine alkaloids, chemicals known to induce fetuses toxicity, have been identified in A. conyzoides. This study aims to evaluate the fetal toxicity of A. conyzoides.Methods: Mated females were randomly assigned to three experimental groups of 8 animals each. Pregnant rats received orally 500 or 1000 mg/kg of 80% hydroalcoholic extract of A. conyzoides, daily from the 17th to the 20th day of gestation. On day 21 of pregnancy, the females were sacrificed. Laparotomy was performed and uterine horns were removed. The number of implants, resorptions, and dead and live fetuses was then recorded. The ovaries were also observed and the corpora lutea were counted.Results: No visible signs of toxicity were observed in females and their pups throughout the study period. However, A. conyzoides (500 and 1000 mg/kg) caused a significant decrease (p<0.01) of fetal weight compared with the control. For the implantation, resorption and morta-lity there was no significant difference between groups.Conclusion: The administration of hydroalcoholic extract of A. conyzoides to female rats in late pregnancy is toxic to the fetuses. This fetal toxicity can be due to the oxidative stress induced by pyrrolizidine alkaloids present in this plant.Â

Fetal Toxicity and Cytotoxicity of Lannea kerstingii Engl and Krause Stem Bark (Anacardiaceae)

Purpose: To evaluate the fetal toxicity and cytotoxicity of L. kerstingii in pregnant rats exposed in the organogenic period.Methods: Mated female rats were randomly assigned to three experimental groups of 8 animals each. Pregnant rats received orally 500 or 1000 mg/kg of 50 % hydroalcohol extract of L. kerstingii, daily from the 17th to the 20th day of gestation. On day 21 of pregnancy, the females were sacrificed. Laparotomy was performed and uterine horns were removed. The number of implants, resorptions, dead and live fetuses were then recorded. The ovaries were also observed and corpora lutea were counted. The cytotoxic effect of L. kerstingii hydroalcohol extract was evaluated on Caco-2 cell lines using MTT (3-(4, 5-dimetylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide) and neutral red uptake assay.Results: No visible signs of toxicity were observed in the female rats and their pups through-out the study period. However, L. kerstingii (500 and 1000 mg/kg) caused a significant decrease (p < 0.01) in fetal weight compared with control. With regard to implantation, resorption and mortality, there was no significant difference between groups. L. kerstingii hydroal-cohol extract (IC50, 29 μg/mL) was more cytotoxic than the aqueous extract (IC50, 141 μg/mL).Conclusion: The administration of hydroalcohol extract of L. kerstingii to female rats in late pregnancy is toxic to the fetus.Keywords: Lannea kerstingii, Fetal toxicity, Cytotoxicity, Mortality, Oxidative stress, Anorexi

GLUE ABUSE IN LOME: INVESTIGATION AND TOXICOLOGICAL STUDY ON WISTAR RATS

Objectives: Volatile substances abuse (VSA) is considered as one of the most dangerous forms of drug abuse leading to serious accidents and fatalities. This study aims to assess the extent and dangers of the sniffing of '' Dia'' glue, used by the vulcanizer to paste the cars' tires.Methods: The first phase of the study involved a survey with vulcanizers of the district I of Lome. The effect of the glue was then evaluated on female wistar rats, by inhalation' in a 1L capacity jar for a period of 5 min at doses of 320 mg/l and 640 mg/l. The rat behavioral changes, driving test, tail flick test, tolerance test and 28 d subchronic toxicity test were carried out.Results: The survey has identified street vendors as glue sniffers (80.95%). The most cited reason for the glue inhalation was the tailism (79.76%) and the presumed effect was to feel stronger (76.19%). On wistar rat, ‘‘Dia'' glue has induced some behavioral changes. It has increased significantly the righting recovery reflex time and the maintaining time of the tail in warm water. After 28 d exposition, 5 min per day, ‘‘Dia'' glue increased significantly (pË‚0.001) the relative weight of the spleen, the AST (pË‚0.001) and ALT (pË‚0.001). It has also induced an anaemia associated with a thrombocytosis. The analysis of the glue by GC-HS-MS has showed a high amount of toluene (65%), a lesser proportion of dimethyl cyclohexane, ethyl acetate and traces of benzene, ethylbenzene and xylene.Conclusion: The sniffing of ‘‘Dia'' glue is very dangerous. Addiction especially that which is done with volatile substances must, therefore, be carefully controlled.Â

CYTOTOXICITY STUDY OF ANTIDIABETIC PLANTS ON NEUROBLASTOMA CELLS CULTURED AT NORMAL AND HIGH GLUCOSE LEVEL

Objective:In diabetes, chronic hyperglycemia causes damage (glucose toxicity) on some cells leading to micro and macro vascular complications. The aim of this study was to investigate the effect of antidiabetic plants extracts in high glucose concentration in vitro. Methods: Phyllanthus amarus (whole plant), Vitex doniana (leaves), Tectona grandis (leaves and trunk bark) and Plumeria alba (roots) hydroalcoholic extract (at the concentrations of 6.25, 25, 75, 125, 250 and 500 µg/ml) were tested for their possible cytotoxicity using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on neuroblastoma cells lines in standard condition (extract alone) and high glucose concentration (extract+50 mM glucose). Results: At concentrations of 6.25 and 25µg/ml, T. grandis bark and leaves and P. amarus induced a significant decrease (p<0.01; p<0.001) on cell viability as compared to controls. The decrease on cell viability was very pronounced in the presence of the extracts plus glucose 50 mM. P. amarus extract becomes increasingly toxic as the concentration of extract increased in the presence of glucose. With P. amarus at 125 µg/ml and glucose at 50 mM, there is no more viable cells in the medium. By contrast, T. grandis bark extract induced a significant reduction of the cytotoxicity in the presence of glucose compared to standard condition. Conclusion:It appears that, only hydroalcoholic extract of T. grandis bark possesses neuroprotective activity in high glucose concentration

Bacterial-based additives for the production of artificial snow: What are the risks to human health?

International audienceFor around two decades, artificial snow has been used by numerous winter sports resorts to ensure good snow cover at low altitude areas or more generally, to lengthen the skiing season. Biological additives derived from certain bacteria are regularly used to make artificial snow. However, the use of these additives has raised doubts concerning the potential impact on human health and the environment. In this context, the French health authorities have requested the French Agency for Environmental and Occupational Health Safety (Afsset) to assess the health risks resulting from the use of such additives. The health risk assessment was based on a review of the scientific literature, supplemented by professional consultations and expertise. Biological or chemical hazards from additives derived from the ice nucleation active bacterium Pseudomonas syringae were characterised. Potential health hazards to humans were considered in terms of infectious, toxic and allergenic capacities with respect to human populations liable to be exposed and the means of possible exposure. Taking into account these data, a qualitative risk assessment was carried out, according to four exposure scenarios, involving the different populations exposed, and the conditions and routes of exposure. It was concluded that certain health risks can exist for specific categories of professional workers (mainly snowmakers during additive mixing and dilution tank cleaning steps, with risks estimated to be negligible to low if workers comply with safety precautions). P. syringae does not present any pathogenic capacity to humans and that the level of its endotoxins found in artificial snow do not represent a danger beyond that of exposure to P. syringae endotoxins naturally present in snow. However, the risk of possible allergy in some particularly sensitive individuals cannot be excluded. Another important conclusion of this study concerns use of poor microbiological water quality to make artificial snow

La pollution par le chlordécone en Guadeloupe et en Martinique (risques sanitaires et mesures de prévention)

BORDEAUX2-BU Santé (330632101) / SudocPOINTE A PITRE-BU (971202101) / SudocSudocFranceF

Ciguatera en Polynésie Française (fondements des traitements traditionnels et comparaison avec la thérapeutique conventionnelle)

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Toxicité des médicaments hypoglycémiants

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Etude des mécanismes épigénétiques de l'acide okadaïque in vitro et influence des polluants environnementaux

L'acide okadaïque (AO) est la principale toxine de dinoflagellés dans l'hépatopancréas des moules. Il a été montré qu'il est largement distribué dans l'organisme des mammifères, surtout dans le tractus intestinal. C'est un promoteur de tumeur. L'AO à faible concentration, induit une méthylation de l'ADN. Donc l'AO peut interférer avec la régulation et l'expression des gènes, la prolifération cellulaire et participer à l'induction de tumeurs par un mécanisme épigénétique dans l'intestin humain. Nous avons utilisé deux ligne es cellulaires, dont une de l'intestin humain, pour étudier ses effets épigénétiques. Les moules peuvent aussi être contaminées par certains métaux (Cd, Hg etc), leurs influences sur la toxicité de l'AO ont été évaluées. Des tests de cytotoxicité ont montré que l'AO réduit la viabilité cellulaire en fonction de la concentration. La peroxydation lipidique augmente de 70 % à 120 %, avec une concentration d'AO de 0,075 à 15 ng/ml. La production de 8OHdG s'accroît de 38 à 52/10 puissance 5 dG et celle de m(puissance 5)dC de (dC+m puissance 5 dC). Parallèlement l'AO inhibe progressivement la transcription du mRNA de la connexine 43 jusqu'à disparition totale, après 24 h d'incubation, conduisant à l'inhibition des GJIC. Ces effets cytotoxiques et épigénétiques sont accrus en présence des métaux. Nos résultats démontrent que l'AO inhibe les GJIC dans les cellules Caco2 comme plusieurs promoteurs de tumeurs, via le stress oxydant qui semble-t-il inhibe les GJIC. Il y a donc un accord parfait avec la littérature. Dans le cas particulier de l'AO, des mutations transverses GC->AT peuvent résulter des processus de réparation des 8OH-dG induites par le stress oxydant. De même l'hyperméthylation induite par de faibles concentrations d'AO peut conduire à la répression des gènes suppresseurs de tumeurs. Il apparaît donc que des effets épigénétiques et des mutations géniques peuvent être impliqués de manière prépondérante dans l'initiation du processus de cancérogenèse de l'AO.Okadaic acid (AO) is the main toxin of dinoflagellates in the hepatopancreas of mussels. It has been shown to be widely distributed in the body of mammals, especially in the intestinal tract. It is a tumour promoter. At low concentrations, OA leads to methylation of the DNA bases. So, OA may interfere with genes regulation, expression, cell proliferation and participate in induction of tumours by epigenetic mechanisms in human intestin. We have used two cell lines (one from human intestin), to study its epigenetic effects. Mussels may be also contaminated by some metals (Cd, Hg etc), their influences on the toxicity of OA were evaluated. Cytotoxicity tests have shown yhat OA reduces cell viability according to the concentration. Lipid peroxidation increases from 70 % to 120 % for OA concentrations of 0.075 to 15 ng. The production of 80HdG increases from 38 to 52 for 10(puissance5)dG similarly to the production of m(puissance5)dCfrom 3 % to 6 % of (dC + m(puissance5)dC). At the same time OA inhibits gradually the transcription of the mRNA of the connexine 43 until total disappearance after 24 h of incubation,leading to inhibition of GJIC. These cytotoxic and epigenic effects are increased in the presence of metals. Our results demonstrate that OA inhibits GJIC in Caco2 cells similarly to a number of tumour promoters via oxidizing stress which seems to inhibit GJIC. There is therefore a complete agreement with the literature. In the particular case of OA, transverse mutations, GC ->AT may result from the repair processes of 80H-dG induced by the oxidizing stress. The hypermethylation of dC may lead to the repression of tumours suppressor genes. It seems, thus, that epigenetics and genomic mutations can be involved prominently in the initiation of the carcinogenesis of OA.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF