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Biomedical subjects

I Chahoud

Publications and source records attributed to I Chahoud.

At least 19 recordsLinked to original sources
PubMed2005

Effects of fentin hydroxide on reproduction of the Japanese quail (Coturnix coturnix japonica).

In a one-generation reproductive study, the fungicidal compound triphenyltin hydroxide (fentin) was administered to adult Japanese quail for 6 weeks at dietary levels of 3 and 30 ppm. Reproduction was significantly impaired in the high-dose group. The principal adverse finding was a marked increase in embryonic mortality, resulting in a lower hatch rate. Furthermore, a reduction in egg production was observed with ongoing duration of treatment. Most of the other reproduction-related parameters were not affected. The in ovo losses are assumed to result from a direct toxic effect of the test substance on chick embryos. At the low dietary level, reproduction was not altered. In contrast to the obvious reproductive toxicity, there was only limited evidence of adverse treatment-related findings in the adult birds. However, because such minor effects as an increase in mean liver weight, which was accompanied by macroscopic liver findings and a decrease in T4 serum concentration, were still seen at 3 ppm, a no-observed-effect level could not be established.

Animals↗
PubMed2005

Relationships between fetal body weight of Wistar rats at term and the extent of skeletal ossification.

We investigated the relationship between fetal body weight at term (pregnancy day 21) and the extent of ossification of sternum, metacarpus, metatarsus, phalanges (proximal, medial and distal) of fore- and hindlimbs and cervical and coccygeal vertebrae in Wistar rats. The relationships between fetal body weight and sex, intrauterine position, uterine horn, horn size, and litter size were determined using historical control data (7594 fetuses; 769 litters) of untreated rats. Relationships between body weight and degree of ossification were examined in a subset of 1484 historical control fetuses (154 litters) which were subsequently cleared and stained with alizarin red S. Fetal weight was independent of horn size, uterine horn side (left or right) or intrauterine position. Males were heavier than females and fetal weight decreased with increasing litter size. Evaluation of the skeleton showed that ossification of sternum, metacarpus and metatarsus was extensively complete and independent of fetal weight on pregnancy day 21. In contrast, the extent of ossification of fore- and hindlimb phalanges and of cervical and sacrococcygeal vertebrae was dependent on fetal body weight. The strongest correlation between body weight and degree of ossification was found for hindlimb, medial and proximal phalanges. Our data therefore suggest that, in full-term rat fetuses (day 21), reduced ossification of sternum, metacarpus and metatarsus results from a localized impairment of bone calcification (i.e., a malformation or variation) rather than from general growth retardation and that ossification of hindlimb (medial and proximal) phalanges is a good indicator of treatment-induced fetal growth retardation.

Animals↗
PubMed2004

Effects of vinclozolin on spermatogenesis and reproductive success in the Japanese quail (Coturnix coturnix japonica).

In a one-generation reproduction study, the major agricultural fungicide vinclozolin was administered to adult Japanese quail for a period of 6 weeks at dietary levels of 125 and 500 ppm. Fertility and reproductive performance were not affected up to the highest concentration, although the examination of additional endpoints in the drakes (spermatid count, histology of the testis) provided some evidence of an inhibition of spermatogenesis at both dietary concentrations. Likewise, there were no indications of systemic toxicity in the adult birds. Plasma hormone concentrations (estradiol, testosterone, progesterone, T3, and T4) showed a large interindividual variance but treatment-related differences between the groups could not be established. There were no clear-cut indications of antiandrogenic effects in quail, although a limited transfer of the test substance into the eggs was proven.

Administration, Oral↗
PubMed2001

Toxicological evaluation of a tea from leaves of Vernonia condensata.

Teas of Vernonia condensata Baker (Asteraceae) are widely used in Brazil for gastro-intestinal disorders and to treat several other diseases. In this study, we evaluated the acute toxicity, embryotoxicity and mutagenicity of a lyophilized aqueous extract (LAE) from V. condensata leaves. Single doses of LAE, up to 5000 mg/kg body weight, were given orally or intraperitoneally to male and female Swiss albino mice. No toxicity was observed after oral administration. The "Approximate Lethal Dose" after intraperitoneal injections was 3400 mg/kg for males and 5000 mg/kg for females. Embryotoxicity was investigated in Han:NMRI mice. LAE (0, 500 and 2000 mg/kg/day) was given by gavage on days 10, 11 and 12, and dams were submitted to caesarean sections on day 18 of pregnancy. Fetuses were weighed, examined for externally visible malformations, and evaluated for skeletal anomalies. Except for a slight reduction of fetal body weight accompanied by signs of delayed ossification at the highest dose, no other embryotoxic effect was noted in the exposed offspring. LAE-induced mutagenicity was evaluated in the Salmonella/microsome assay without and with S9 mixture. LAE, tested up to 5000 microg/plate, was not mutagenic to tester strains TA97a, TA98 and TA100. Results therefore suggest that V. condensata aqueous extracts present low acute toxicity and pose neither teratogenic nor mutagenic risks.

Animals↗
PubMed2000

Developmental toxicity of the HIV-protease inhibitor indinavir in rats.

BACKGROUND: Indinavir is an antiviral agent used for the treatment of HIV infection. We studied its developmental toxicity in rats. METHODS: Pregnant animals were treated orally with 500 mg indinavir/kg body weight (bw) from day 6 to 15 of gestation (once daily) or from day 9 to 11 (twice daily). Fetuses were evaluated for external and skeletal anomalies on day 21 of gestation. In addition, 19 rats were treated from day 9 of gestation to day 24 postnatally with 500 mg indinavir/kg bw once daily; a control group of 17 rats was treated with the vehicle accordingly. Developmental landmarks were recorded. Sixteen offspring each were studied on postnatal days 7, 14, 21, and 35 for hepatic enzyme activity. Liver tissue was examined by electron microscopy. RESULTS: Fetal examination on day 21 of pregnancy showed no treatment-related effects on number, weight, and viability of the fetuses; however, an increased incidence was noted in the supernumerary ribs and variations of the vertebral ossification centers in both indinavir-treated groups. Postnatal evaluation showed delayed fur development, eye opening, and descensus testis. The most striking finding was unilateral anophthalmia, observed in 7 pups (3%) from 2 out of 19 litters exposed to indinavir, but not in controls. Only minor changes in hepatic monooxygenase activities occurred in dams. Electron microscopy of liver samples showed hepatocellular inclusions of lipids and myelin figure-like structures in maternal livers and infiltration with granulocytes in offspring livers. CONCLUSIONS: Further studies on reproductive toxicity, including combinations of three or more antiretroviral agents as used therapeutically, are needed to determine the hazards of such a treatment.

Abnormalities, Drug-Induced↗
PubMed2000

PCDDs, PCDFs, PCBs, and other organochlorine compounds in human milk from Rio de Janeiro, Brazil.

The levels of polychlorinated dibenzo-p-dioxins (PCDDs) and -furans (PCDFs), polychlorinated biphenyls (PCBs), and other organochlorine compounds were determined in a pooled sample of breast milk from 40 mothers (first lactation: 33; second lactation: 7, age: 15-38 years) living in the urban area of Rio de Janeiro County, Brazil, in 1992. Mothers were breastfeeding only one infant and milk was collected between 4 and 6 weeks after delivery. The results showed a dioxin equivalent concentration of 8.1 pg I-TEq/g milk fat. The levels of other chlorinated compounds (micrograms per gram of milk fat) were as follows: PCBs (total), 0.15; alpha-HCH, 0.001; beta-HCH, 0.27;gamma-HCH, 0.005; HCB, 0.012; DDT (total), 1.7; dieldrin, 0.023, and cis-heptachlor epoxide, 0.008. These results suggest that human background contamination by PCDD/Fs, PCBs, and HCB in Rio de Janeiro is lower than that generally found in industrialized countries.

Adolescent↗
PubMed2000

Establishment and characterization of the follicular thyroid carcinoma cell line ML-1.

The present study focuses on the establishment and characterization of a new follicular thyroid carcinoma cell line. The human cell line ML-1 was derived from a dedifferentiated follicular thyroid carcinoma relapse, which progressed despite preceding surgery followed by two radioiodine therapies. More than 90% of the cells of this line express thyroglobulin, chondroitin sulfate, and vimentin antigens, but only about 70% show cytokeratin filaments and a negative surface charge density such as human erythrocytes. More importantly, cells of this line are able to take up iodine and/or glucose both in vitro and in vivo and to secrete thyroglobulin, chondroitin sulfate, and fibronectin into the interstitial space. In addition, triiodothyronine is released constitutively into culture supernatants. Moreover, it is also suitable for xenotransplantation studies because it is tumorigenic in NMRI nude mice in vivo. The cell line forms tumors with follicular structures when transplanted to nude mice. Due to these unique features the ML-1 cell line can be considered as a very suitable test model for pharmacological and cell biological studies. Since chemicals may interfere with the production of thyroid hormones, this cell line represents also a tool for toxicological investigations.

Adenocarcinoma, Follicular↗
PubMed1999

Male reproductive toxicity and beta-luteinizing hormone gene expression in sexually mature and immature rats exposed to 2-bromopropane.

1. The reproductive effects of 2-bromopropane (2-BP) in sexually mature and immature male Sprague-Dawley rats were investigated. The animals were randomly divided into three treatment groups and one control group each of which comprised six mature and six immature rats. The treated groups were injected s.c. 200, 600 and 1800 mg/kg of 2-BP on 5 days a week for 5 - 7 weeks and the control group received the vehicle. 2. The absolute and relative testis weights were significantly reduced in 600 and 1800 mg/kg b.w. dose groups in both mature and immature rats. The absolute epididymis, prostate, seminal vesicle, and pituitary weights and the relative epididymis weights, however, were significant only at the highest dose level used in both mature and immature rats. 3. The sperm concentration and sperm viability in epididymal duct decreased and the percentage of abnormal sperm increased in a dose-dependent manner in both mature and immature rats. Additionally, serum testosterone level was significantly decreased in all dose groups in mature rats, and was significantly reduced only in the group treated with the middle and highest dose in immature rats. 4. In both mature and immature rats treated with 200 and 600 mg/kg, the seminiferous tubules were atrophied and all types of germ cells were decreased in number. At the highest dose level, the effect was more marked showing severely atrophied seminiferous tubules and a complete loss of all types of germ cells. 5. The mating, pregnancy and fertility indices were significantly reduced in the 600 and 1800 mg/kg groups. Additionally, at the highest dose group the number of implantations and viable fetuses per litter were reduced and the resorption rate was increased significantly. 6. In the mature rats, the beta-LH gene expression increased significantly in the 1800 mg/kg group when compared to the control group. 7. It can be concluded that 2-BP induces alterations in both neuro-endocrine axis and the reproductive tract under the present experimental conditions. The no observed adverse effect level (NOAEL) in this study could be estimated to be lower than 200 mg/kg/b.w. based on the alteration in testicular morphology as well as on sperm parameters observed at the dose level of 200 mg/kg.

Animals↗
PubMed1998

Reproductive toxicity and tissue concentrations of low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin in male offspring rats exposed throughout pregnancy and lactation.

The effects of low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the reproductive system of male offspring rats were examined. The dams were treated subcutaneously 2 weeks prior to mating and throughout mating, pregnancy, and lactation. They received an initial loading dose of 25, 60, or 300 ng TCDD/kg body wt, followed by a weekly maintenance dose of 5, 12, or 60 ng TCCD/kg body wt (TCDD 25/5, TCDD 60/12, and TCDD 300/60). Three dams per group were killed on Gestation Day 21 and the fetuses were removed. The concentration of TCDD in the maternal liver and fat was measured. After birth, developmental landmarks in male rats were monitored. At weaning, the concentration of TCDD in the offspring liver and testis was determined. Effects on male reproduction were studied on Postnatal Days (PND) 70 and 170. At weaning, the concentration of TCDD in the offspring liver was 0.24, 0.39, and 1.78 ng/g in the TCDD 25/5, TCDD 60/12, and TCDD 300/60 groups, respectively. In the testes, the concentration of TCDD was 0.25 ng/g in the TCDD 25/5 and TCDD 60/12 groups and 0.28 ng/g in the TCDD 300/60 group. The number of sperm per cauda epididymis was reduced in TCDD groups at puberty and at adulthood. Daily sperm production was permanently decreased as was the sperm transit rate in the TCDD-exposed male rats, thus increasing the time required by the sperm to pass through the cauda epididymis. Moreover, the male rats of the TCDD groups showed an increased number of abnormal sperm when investigated at adulthood. Similarly, mounting and intromission latencies were significantly increased in the TCDD 25/5 and TCDD 300/60 groups. In the highest dose group, serum testosterone concentration was decreased at adulthood. Likewise, in this dose group permanent changes including pyknotic nuclei and the occurrence of cell debris in the lumen were revealed. The lowest adverse effect level and the no observed effect level can be estimated to be substantially lower than the estimated daily dose of the lowest dose which is 0.8 ng/kg body wt/day. Sperm parameters were more susceptible than the other end points investigated. However, the question as to whether such doses exposed throughout gestation and lactation induce subtle changes in humans remains to be determined.

Adipose Tissue↗
PubMed1998

Reproductive toxicity and tissue concentrations of 3,3',4,4'-tetrachlorobiphenyl (PCB 77) in male adult rats.

1 The aim of this study was to ascertain the reproductive effects of PCB 77 on adult male rats and to determine its concentration in the liver and testis. Adult male rats (n = 15/group) were treated subcutaneously with a single dose of 18 mg/kg bw (PC18) or with 60 mg/kg bw (PC60). The substance was dissolved in a 10 ml volume of peanut oil/kg. Control rats received the same volume of the vehicle. The reproductive effects as well as the concentration of PCB 77 in the liver and testis were investigated 1, 4 and 8 weeks after treatment. 2 In both groups, the daily sperm production (DSP; x10(6)) remained permanently reduced in the PC18 as well as in the PC60 groups throughout the entire investigation period (DSP week 8: control: 31 +/- 7; PC18: 22 +/- 5; PC60: 20 +/- 7). The sperm number (x10(6)) per cauda epididymis was affected only at the 1st and 4th week after treatment (control week 1: 211 +/- 67; PC18 week 1: 135 +/- 62; PC60 week 1: 142 +/- 49). Moreover, a significant increase in the percentage of abnormal sperm was observed 4 weeks following treatment in the PC18 and PC60 groups and 8 weeks after treatment in the PC60 group. Abnormal tails were the most frequent changes observed. 3 The relative testicular and prostata weights (g) were slightly increased in the PC60 group at the 1st and 4th week following treatment (testis weight: control/I: 0.46 +/- 0.02; PC60/I: 0.51 +/- 0.03). 4 The serum testosterone concentrations and effects on testis morphology were not reported. 5 The maximum concentration of PCB 77 was detected in the liver and testis 1 week after treatment. The concentration declined 4 weeks after treatment in both organs, but still a significant amount of PCB 77 was detectable in the liver as well as in the testis 8 weeks after treatment. 6 The results demonstrate that PCB 77 affects sperm variables when applied to adult rats and that the elimination of PCB 77 in the testis parallels that of the liver.

Animals↗
PubMed1998

Effects on developmental landmarks and reproductive capability of 3,3',4,4'-tetrachlorobiphenyl and 3,3',4,4',5-pentachlorobiphenyl in offspring of rats exposed during pregnancy.

1. Pregnant Wistar rats were treated orally with a single dose of 100 microg 3,3',4,4'-tetrachlorobiphenyl (PCB 77)/kg b.w. or 10 microg 3,3',4,4',5 pentachlorobiphenyl (PCB 126)/kg b.w. on day 15 of pregnancy. The control rats received peanut oil at the same day. Developmental landmarks were assessed in all offspring rats and reproductive effects of PCB 77 and PCB 126 on male offspring were studied on postnatal day 65 (at puberty) and on postnatal day 140 (at adulthood). 2. The ano-genital distance as well as the ratio ano-genital distance to body length was reduced in male pups of the PCB 126 group and the age at vaginal opening was significantly delayed in the female pups. 3. Testis, brain weights and daily sperm production were permanently increased and seminal vesicle weights were decreased in male offspring of the PCB 77 group. In male rats of PCB 126 group, the brain weights were permanently increased and ventral prostate weights permanently reduced. In both PCB groups, however, serum testosterone concentration was reduced only at adulthood. Additionally, the male rats of the PCB 126 group showed alterations in sexual behavior. In these rats the number of mounts with intromissions was significantly increased. 4. The results of this study show that PCB 126 elicits some TCDD-like reproductive effects after in utero exposure, while the reproductive effects of in utero exposure to PCB 77 on male offspring may be attributed to the neonatal hypothyroidism induced by the substance during early fetal development. Further studies using multiple doses and providing thyroid hormone data will be necessary to support this hypothesis.

Administration, Oral↗
PubMed1998

Study of the effects of beta-myrcene on rat fertility and general reproductive performance.

beta-Myrcene (MYR) is a monoterpene found in the oils of a variety of aromatic plants including lemongrass, verbena, hop, bay, and others. MYR and essential oils containing this terpenoid compound are used in cosmetics, household products, and as flavoring food additives. This study was undertaken on investigate the effects of MYR on fertility and general reproductive performance in the rat. MYR (0, 100, 300 and 500 mg/kg) in peanut oil was given by gavage to male Wistar rats (15 per dose group) for 91 days prior to mating and during the mating period, as well as to females (45 per dose group) continuously for 21 days before mating, during mating and pregnancy, and throughout the period of lactation up to postnatal day 21. On day 21 of pregnancy one-third of the females of each group were submitted to cesarean section. Resorption, implantation, as well as dead and live fetuses were counted. All fetuses were examined for external malformations, weighed, and cleared and stained with Alizarin Red S for skeleton evaluation. The remaining dams were allowed to give birth to their offspring. The progeny was examined at birth and subsequently up to postnatal day 21. Mortality, weight gain and physical signs of postnatal development were evaluated. Except for an increase in liver and kidney weights, no other sign of toxicity was noted in male and female rats exposed to MYR. MYR did not affect the mating index (proportion of females impregnated by males) or the pregnancy index (ratio of pregnant to sperm-positive females). No sign of maternal toxicity and no increase in externally visible malformations were observed at any dose level. Only at the highest dose tested (500 mg/kg) did MYR induce an increase in the resorption rate and a higher frequency of fetal skeleton anomalies. No adverse effect of MYR on postnatal weight gain was noted but days of appearance of primary coat, incisor eruption and eye opening were slightly delayed in the exposed offspring. On the basis of the data presented in this paper the no-observed-adverse-effect level (NOAEL) for toxic effects on fertility and general reproductive performance can be set at 300 mg of beta-myrcene/kg body weight by the oral route.

Acyclic Monoterpenes↗
PubMed1997

Terminology of developmental abnormalities in common laboratory mammals (version 1).

This paper presents the first version of an internationally-developed glossary of terms for structural developmental abnormalities in common laboratory animals. The glossary is put forward by the International Federation of Teratology Societies (IFTS) Committee on International Harmonization of Nomenclature in Developmental Toxicology, and represents considerable progress toward harmonization of terminology in this area. The purpose of this effort is to provide a common vocabulary that will reduce confusion and ambiguity in the description of developmental effects, particularly in submissions to regulatory agencies worldwide. The glossary contains a primary term or phrase, a definition of the abnormality, and notes, where appropriate. Selected synonyms or related terms, which reflect a similar or closely related concept, are noted. Nonpreferred terms are indicated where their usage may be incorrect. Modifying terms used repeatedly in the glossary (e.g., absent, branched) are listed and defined separately, instead of repeating their definitions for each observation. Syndrome names are generally excluded from the glossary, but are listed separately in an appendix. The glossary is organized into broad sections for external, visceral, and skeletal observations, then subdivided into regions, structures, or organs in a general overall head to tail sequence. Numbering is sequential, and not in any regional or hierarchical order. Uses and misuses of the glossary are discussed. Comments, questions, suggestions, and additions from practitioners in the field of developmental toxicology are welcomed on the organization of the glossary as well as on the specific terms and definitions. Updates of the glossary are planned based on the comments received.

Animals↗
PubMed1997

The area under the concentration-time curve of all-trans-retinoic acid is the most suitable pharmacokinetic correlate to the embryotoxicity of this retinoid in the rat.

Earlier studies with etretinate and its metabolite acitretin suggested that area under the concentration-time curve (AUC) is the most suitable pharmacokinetic correlate to etretinate-induced teratogenesis. In an attempt to test this hypothesis with respect to the embryotoxic effects of all-trans-retinoic acid (all-trans-RA), we determined the embryotoxicity and plasma pharmacokinetics of all-trans-RA and its metabolites following administration of all-trans-RA to Wistar rats on Gestational Day (GD) 9, either subcutaneously (sc; dose levels 1, 3, or 5 mg/kg body mass) or orally (po; 5 mg/kg body mass). The 5 mg/kg dose of all-trans-RA was not embryotoxic when administered orally but led to high rates of embryolethality and skeletal defects following sc treatment. Determination of retinoids by HPLC showed that all-trans-RA reached similar maximum plasma concentrations (C(max)) after both dosing regimens, but its plasma AUC was ca. threefold higher after sc injection than po administration due to the slower uptake rate of the drug and its limited detoxification via beta-glucuronidation following sc injection. Furthermore, retinoid analysis in rat tissues (liver, kidney, duodenum, and jejunum), collected 1 hr after sc or po administration of 5 mg all-trans-RA/kg body mass on GD 9, confirmed that formation of all-trans-retinoyl-beta-glucuronide was much more extensive after po than after sc administration. Finally, linear regression analysis of either C(max). or AUC values of all-trans-RA in rat plasma and fetal abnormality rates showed that AUC values are better correlated with the embryotoxic outcome than C(max) [AUC-based correlation coefficient (r) > 0.90; C(max)-based r < 0.43]. Our findings establish the relevance of the AUC of all-trans-RA, and not its C(max), as the most appropriate pharmacokinetic marker of embryonic exposure and embryotoxic potency of all-trans-RA and stress the importance of the duration of exposure as a major determinant of embryotoxic outcome for retinoids.

Abnormalities, Drug-Induced↗