Morphological and Skeletal Abnormalities Induced by Rolapitant: An Antiemetic Agent (original) (raw)
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Rolapitant: Effects of an Antiemetic Agent on the Growth of Developing Chick Embryo
International Journal of Medical Research & Health Sciences,, 2021
Aim: The purpose of this study was to determine the effect of Rolapitant, an antiemetic agent, on chick embryo development in 200 white leghorn chicken eggs used that met the inclusion-exclusion criteria. Material and method: The present study utilized 200 eggs, randomly assigned to experimental groups A and B and control groups a and b. Eggs incubated in the presence of Rolapitant had their Rolapitant dose increased on the fifth day of incubation from 0.18 mg to 0.36 mg. In contrast to the control groups, all of the subjects in the treatment groups received the same amount of normal saline. Eggs were broken on the twentieth day of incubation, and embryos were extracted on the same day. Results: The weight and CRL of the chick embryos were measured, and gross anatomical malformations were observed-the percentile lethality of Rolapitant increase with dose with the odds ratio of 1.175 and 1.313. While analyzing the abnormal weight and abnormal CR length due to the effects of Rolapitant, a significant difference was observed. In each case, an increased t-value concerning an increase in dose shows the lethality of Rolapitant. Conclusion: The present study observed an increased mortality rate and a decrease in weight and crown-rump length following a double dose of Rolapitant. The author remanded additional research with a larger sample size to improve the current observation's reliability and generalizability.
The chick was chosen as a model because it is more readily available than rats or mice and its organogenesis is analogous to that of humans. Rolapitant is a highly potent, powerful antagonist of the neurokinin-1 receptor, featuring a high degree of infiltration to the brain. The study aimed to assess the morphological and histopathological analysis of the brain (cerebral cortex) of growing chick embryos in response to the rolapitant's effect. Three hundred fertilised white leghorn chicken eggs were utilised, separated into five control groups (C1 to C5) and five experimental groups (E1 to E5), each with thirty eggs. On the fifth day of incubation, eggs from five experimental groups were exposed to different concentrations of rolapitant at 0.00039 mg, 0.0005 mg, 0.00075 mg, 0.001 mg, and 0.00125 mg respectively, whilst five control groups received the same concentration of normal saline. Chick brains were obtained and weighed. The cerebral cortex (brain) was sectioned and stained to examine the histopathological abnormalities. A significant growth retardation and decreased weight of the brain of experimental groups were noted. The number of chick embryos with abnormal "Histopathological findings such as" neuronophagia and perineural vacuolation in the cerebral cortex was also significant in experimental groups E4 and E5 (p-value < 0.05). Mild to moderate degenerative changes in the cerebral cortex of experimental groups E3, E4 and E5 and some haemorrhagic spots in experimental groups E4 and E5 were also noted. When taken in large doses, the rolapitant demonstrated its toxic effects on the brain of chick embryos.
The Teratogenic Effects of the Insecticide Pyriproxyfen on the Developing Chick Embryos
Egyptian Journal of Zoology
Pyriproxyfen (PPF) is a juvenile hormone analogue insecticide that is often used as a larvicide against a wide range of insect pests. The present study was designed to investigate its teratogenic effects on the embryonic development of the chick. First, the median lethal dose (LD50) of the commercial PPF was determined. Accordingly, three sub-lethal doses (15, 30, 45 µg/egg) were selected for injection into the air space of the eggs after 24 hours of incubation. The eggs were opened on the embryonic days (EDs) 7 and 14, and the embryos were examined for morphometric changes and the presence of malformations. The PPF treatment induced growth retardation and reduction in head and eye sizes as reflected by a reduction in wet body weights, crown-rump lengths, anterior-posterior head lengths, and eye diameters. These morphometric alternations were mild or moderate on ED7, but more apparent on ED14. Also, significant reductions in the lengths of the forelimb and hindlimb parts were recorded with high-dose treatment on ED14. Obviously, there was high percentage of malformations among ED7 individuals in the form of hematoma, ventral body wall defect, limb deformities, microphthalmia, and microcephaly. However, on ED14 the embryos exhibited significant hematoma, microcephaly, delay feather, delay beak, microphthalmia in all treated groups, and limb deformities in the group that received the high dose. Other abnormalities included edema, anophthalmia, short neck, short tail, caudal regression, microtia, and microblepharon were also recorded. These findings revealed that PPF has potentially teratogenic effects on the development of the chick embryos. Pyriproxyfen-induced teratogenicity in chick embryos
Teratogenic Effects of Chlorantraniliprole on chick embryos (Gallus gallus domesticus)
Indian Journal of Animal Research, 2017
The present study was designed to assess the teratogenic effects of Chlorantraniliprole on chick embryos (Gallus gallus domesticus). Different doses of commercial Chlorantraniliprole (0.1, 0.5, 1.0 and 1.5µl/1000µl/egg, in four experimental groups B, C, D, and E respectively) were injected into the yolk sac of eggs before incubation. Embryos were recovered at day 12 of incubation. The mortality rate gradually increased from lower to higher doses. A total of twelve morphometric parameters viz., wet body weight, crown rump length, anterior posterior head diameter, eye diameter, beak length, neck length, humor length, radius and ulna length, metacarpus length, femur length, fibula length and metatarsus length were recorded and compared with control group. These quantitative parameters indicated significant (p>0.05) decreases in all treated groups compared to control group. While the qualitative anomalies such as microcephaly, hydrocephaly, edematous swelling, hematoma formation, abn...
Toxicity Study of Chlorzoxazone and Isosorbide Dinitrate using Chick Embryo
Biosciences, Biotechnology Research Asia, 2022
Number of potential drugs are underutilized due to a lack of availability of teratological data. Isosorbide Dinitrate is a saviour drug in angina prophylaxis while chlorzoxazone is a skeletal muscle relaxant and there is no adequate teratogenic study performed till date. This study aims to assess the teratological effect of these drugs on vital organs using the chick embryo model. White Leghorn's (Gallus gallus domesticus) fertilised chicken eggs were acquired from shivneri agro and hatcheries Nashik and divided into five groups (n=10) as Control, nonteratogenic, teratogenic, chlorzoxazone, and Isosorbide Dinitrate. The drug was injected via yolk inoculation and after inoculation; the eggs were re-incubated at 37.5-37.8°C and 50-60% RH for 21 days. Then the embryos were harvested and evaluated for morphological and histopathological changes. The gross macroscopic examination of Isosorbide Dinitrate and chlorzoxazone treated chicks were normal. The development of the embryo was found shunted in Isosorbide Dinitrate treated group. Microscopic abrasions found in Isosorbide Dinitrate treated group are myocardial congestion, hemorrhage, hydropic degeneration, dislocation of the nucleus, splitting of cells, and infiltration of cells at all three doses. No teratogenic response was observed in chlorzoxazone treated group hence found to be safe. Teratogenic effect of Chlorzoxazone and isosorbide dinitrate in chick embryo provided notable details. Chlorzoxazone was found to be safe in chick embryos in the developmental phase, While Isosorbide dinitrate at highest dose was found toxic and so, it is inadvisable for its utilization in pregnancy.
Teratogenic Effects of ACE Inhibitors (Telmisartan) on the Development of Chick Embryos
The potential teratogenic effects of Telmisartan were investigated on developing chick embryos. A dosage of 0.025mL of 1mg/mL of the test agent served as the treatment group while 9% normal saline solution was introduced to the control group. The test agent was tested on developing chick embryos, specifically introduced on the 5th day of incubation. Morphological and anatomical abnormalities were checked and tallied on observation on both stages – embryological development and fully developed and emerged chicks. The results of this study, specifically tested via scaling by degree of malformations (qualitative) and Mann Whitney U test (quantitative) at alpha level 0.05 with U = 3 & CV = 5, proved that the ACE inhibitor drug Telmisartan is significantly teratogenic on developing chick embryos.
Environmental Toxicology, 2010
Developmental toxicity of two different classes of commercial formulations of insecticides was studied by in ovo treatment of fertilized Rhode Island Red eggs. The first one was a combination of chlorpyrifos and cypermethrin and the second one was spinosad, a fermentation product of soil bacterium, Actinomycetes. In this study, the combination pesticide and spinosad of different concentrations were administered as a single dose in ovo in volumes of 50 μL per each egg on day “0” of incubation. Embryonic growth and development, morphological and skeletal malformations, and hatchability were assessed. The combination insecticide induced explicit alterations in the embryonic growth and development and resulted in malformations particularly to the axial and appendicular skeletal structures, whereas the changes were trivial in case of the spinosad exposure. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.
Toxicological effects of diclofenac in four avian species
Avian Pathology, 2008
The objective of the present study was to investigate the toxico-pathological effects of diclofenac in different avian species including broiler chicks (Gallus gallus, 15 days old), pigeons (Columba livia, 3 months old), Japanese quail (Coturnix japonica, 4 weeks old) and mynah (Acridotheres tristis, independent young). For each species, five groups each containing 10 birds were maintained and administered diclofenac sodium orally at dose rates of 0, 0.25, 2.5, 10 and 20 mg/kg body weight, respectively, for seven consecutive days. Clinical signs in all species included depression, somnolence, decreased body weight and mortality. Severity of clinical disease increased in a dose-related manner and was most severe in broiler chicks, followed by pigeons, Japanese quail, and was least severe in mynah. Serum creatinine levels were elevated in all species. Serum urea levels varied non-significantly in broiler birds, significantly decreased in pigeons and significantly elevated in Japanese quail and mynah. Broiler chicks and pigeons administered 10 and 20 mg diclofenac/kg had visceral gout; however, this was not observed in Japanese quail and mynah. The kidneys and liver were enlarged in all species. Histologically, the kidneys of all species showed acute renal necrosis and the livers had fatty change and necrosis of hepatocytes. The kidneys and liver of broiler chicks and pigeons given 10 and 20 mg/kg diclofenac also exhibited uric acid crystal aggregates (tophi) and associated lesions in the parenchyma.Effets toxicologiques du diclofenac chez quatre espèces aviairesL'objectif de cette étude a été d'investiguer les effets toxico-pathologiques du diclofenac chez différentes espèces aviaires incluant des poussins de chair (Gallus gallus, de 15 jours), des pigeons (Columba livia, de 3 mois) des cailles japonaises (Coturnix japonica, de 4 semaines), et des mainates (Acridotheres tristis, jeune indépendant). Pour chaque espèce, cinq groupes de 10 sujets ont reçu oralement du sodium de diclofenac aux doses respectives de 0, 0, 25, 2, 5, 10 et 20 mg / kg de poids du corps, durant sept jours consécutifs. Dans toutes les espèces, les symptômes comprenaient de la prostration, de la somnolence, une perte de poids et de la mortalité. La sévérité de la maladie a augmenté en fonction de la dose et a été plus importante chez les poussins de chair, suivis par les pigeons, les cailles japonaises, et a été moins importante chez les mainates. Les niveaux en créatine sérique ont été élevés chez toutes les espèces. Les niveaux en urée sérique ont varié de façon non significative chez les poussins de chair, ont diminué significativement chez les pigeons et ont augmenté significativement chez les cailles japonaises et les mainates. Les poussins de chair et les pigeons qui ont reçu 10 et 20 mg de diclofenac / kg présentaient de la goÛte viscérale, cependant, ceci n'a pas été observé chez les cailles japonaises ni les mainates. Les reins et le foie ont été hypertrophiés chez toutes les espèces. Histologiquement, les reins de toutes les espèces ont montré une nécrose rénale aiguë et les foies présentaient des lésions de surcharge graisseuse et une nécrose des hépatocytes. Les reins et le foie des poussins de chair et des pigeons qui ont reçu 10 et 20 mg de diclofenac / kg ont également montré des agrégats cristallins d'acide urique et des lésions associées dans le parenchyme.Toxikologische Wirkungen von Diclofenac in vier VogelspeziesZiel dieser Studie war es, die toxikopathologischen Wirkungen von Diclofenac in verschiedenen Vogelspezies einschließlich Broiler (Gallus gallus, 15 Tage alt), Tauben (Columba livia, 3 Monate alt), Wachteln (Coturnix japonica, 4 Wochen alt) und Hirtenstaren (Acridotheres tristis, flügge Jungvögel) zu untersuchen. Von jeder Spezies wurden fünf Gruppen mit jeweils 10 Vögeln gehalten, die an sieben aufeinander folgenden Tagen oral 0, 0,25, 2,5, 10 oder 20 mg Diclofenac-Natriumsalz/kg Körpergewicht (KGW) erhielten. Die klinischen Symptome umfassten Depression, Somnolenz, Wachstumsverzögerung und Mortalität. Der Schweregrad der klinischen Symptome stieg dosisabhängig an und war am höchsten bei den Broilerküken gefolgt von den Tauben, Wachteln und Hirtenstaren. Die Serumkreatiningehalte waren bei allen Spezies erhöht. Die Serumharnstoffwerte wiesen bei den Broilern nicht signifikante Unterschiede auf, nahmen bei den Tauben signifikant ab und stiegen bei den Wachteln und Hirtenstaren signifikant an. Die Broilerküken und die Tauben, denen 10 und 20 mg Diclofenac/kg KGW verabreicht worden war, entwickelten eine Viszeralgicht, während dies bei den Wachteln und Hirtenstaren nicht beobachtet wurde. Die Nieren und Lebern waren bei allen Spezies vergrößert. Histologisch zeigten die Nieren bei allen Spezies akute renale Nekrose und die Lebern fettige Degeneration und Nekrose der Hepatozyten. Die Nieren und Lebern der Broilerküken und Tauben, die 10 und 20 mg Diclofenac/kg KGW erhalten hatten, wiesen außerdem Harnsäurekristalaggregate (Tophi) sowie damit verbundene Läsionen in den Parenchymen auf.Efectos toxicológicos del diclofenaco en cuatro especies aviaresEl objetivo de este estudio fue investigar los efectos toxico-patológicos del diclofenaco en cuatro especies aviares distintas que incluían pollos de engorde (Gallus gallus, 15 días de vida), palomas (Columba livia, 3 meses de edad), codorniz (Coturnix japonica, 4 semanas de edad), Mainá común (Acridotheres tristis, jóvenes). Para cada especie, se incluyeron cinco grupos de 10 aves cada uno a los que se administró diclofenaco sódico oralmente a dosis de 0, 0.25, 2.5, 10 and 20 mg / kg peso vivo respectivamente, durante siete días consecutivos. En todas las especies los signos clínicos incluyeron depresión, somnolencia, disminución del peso vivo y mortalidad. La gravedad de los signos clínicos aumentó en relación con la dosis y fue más grave en los pollos broiler, seguido de las palomas, las codornices y la menor gravedad se observó en los Mainás. Los niveles de creatinina en suero fueron altos en todas las especies. Los niveles de urea no variaron de forma significativa en los broiler, disminuyeron significativamente en las palomas, y aumentaron significativamente en las codornices y los mainás. Los broiler y palomas a los que se administraron 10 y 20 mg de diclofenaco/kg desrrollaron gota visceral, sin embargo, esto no se observó en las codornices ni en los mainás. Se observó un aumento de tamaño de los riñones e hígado en todas las especies. Histológicamente, en todas las especies se observó necrosis renal aguda e hígado graso asociado a necrosis de hepatocitos. En los broiler y palomas tratados con 10 y 20 mg/kg de diclofenaco se observó agregados de cristales de ácido úrico (tofus) asociados a lesiones en el parénquima de riñones e hígado.
The chick embryo in toxicology: an alternative to the rabbit eye
Food and Chemical Toxicology, 1985
The chorioallantoic membrane (CAM) of the chick embryo is readily accessible for experimentation. It is a complete tissue that responds to injury with classical inflammatory reactions. It is limited to the late phase of embryologic life. and is without the sense of pain. Focal topical application of various household products onto the CAM results in local injury and reactions that differ in severity from one product to another. For any single product, tested as a sequence of dilutions on a series of membranes, the CAM responds with decreasing intensity that parallels the decreasing dosage. The membrane is prepared for study according to the method of Zwilling (Transplantn Bull 1959, 6, 115). The test material is applied in a Teflon ring to the 14-day-old CAM, to localize the application site. The macroscopic response is scored on day 17 of incubation. The results of analysis of histological preparations are found to correlate with macroscopic appearance. When a series of preparations was ranked according to the severity of the response each induced on the CAM, there was a good correlation with the ranking of the same preparations in the Draize test.
Embryotoxic effects of in-ovo triclosan injection to the yellow-legged gull
Chemosphere, 2018
Triclosan (TCS) is an antimicrobial agent used in diverse personal care products that is considered as an emerging contaminant of both aquatic and terrestrial ecosystems. Although TCS aquatic ecotoxicity is well known, information on the presence and effects on terrestrial organisms is still scarce. This study was aimed at exploring the embryotoxicity of TCS to the yellow-legged gull (Larus michahellis) induced by the in-ovo injection of 150 ng TCS/g egg weight. Effects of TCS on embryo morphological traits (i.e. body mass, tarsus length and head size). Moreover, oxidative and genetic effects were assessed in the embryo liver, by measuring the amount of reactive oxygen species (ROS), the activity of antioxidant (superoxide dismutase and catalase) and detoxifying (glutathione Stransferase-GST) enzymes, the levels of lipid peroxidation and DNA fragmentation. After the injection, the concentration of TCS measured in the yolk of unincubated eggs (159 ± 35 ng/g wet weight, ww) was close to the expected concentration. Triclosan was found in residual yolk (2.9 ± 1.1 ng/g ww), liver (2.3 ± 1.1 ng/g ww) and brain (0.2 ± 0.1 ng/g ww) of embryos soon before hatching. Triclosan did not significantly affect embryo morphological traits, while it increased ROS levels and promoted GST activity, inducing the onset of both oxidative and genetic damage. This study demonstrated, for the first time in a wild euriecious bird species with mixed habits, that TCS can be maternally transferred to developing embryos, representing a potential threat for offspring.