Assuntos
Rotavirus , Animais , Povo Asiático , Bovinos , Humanos , Lactente , Projetos de Pesquisa , VacinaçãoRESUMO
BACKGROUND: A heat-stable bovine-human rotavirus reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was developed in India. In this study, the vaccine was tested for safety, immunogenicity and clinical lot-to-lot consistency. METHODS: This was a Phase III, open label, randomized, equivalence design study. The primary objective was to demonstrate lot-to-lot consistency of BRV-PV. Subjects were randomized into four arms, three arms received Lots A, B, and C of BRV-PV and the control arm, received Rotarix®. Three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given at 6, 10, and 14â¯weeks of age. Blood samples were collected four weeks after the third dose to assess rotavirus IgA antibody levels. The three lots of BRV-PV were equivalent if the 95% Confidence Intervals (CIs) of the geometric mean concentration (GMC) ratios were between 0.5 and 2. Solicited reactions were collected by using diary cards. RESULTS: The study was conducted in 1500 randomized infants, of which 1341 infants completed the study. The IgA GMC ratios among the three lots were around 1 (Lot A versus Lot B: 1.07; Lot A versus Lot C: 1.06; and Lot B versus Lot C: 0.99). The 95% CIs for the GMC ratios were between 0.78 and 1.36. The IgA GMCs were: BRV-PV group 19.16 (95% CI 17.37-21.14) and Rotarix® group 10.92 (95% CI 9.36-12.74) (GMC ratio 1.75; 90% CI 1.51-2.04). Seropositivity rates were 46.98% (95% CI 43.86-50.11) and 31.12% (95% CI 26.17-36.41). The incidence of solicited reactions was comparable across the four arms. No serious adverse events were associated with the study vaccines, except two gastroenteritis events in the BRV-PV groups. CONCLUSION: Lot-to-lot consistency of BRV-PV was demonstrated in terms of GMC ratios of IgA antibodies. The vaccine safety and immunogenicity profiles were similar to those of Rotarix®. Clinical Trials.Gov [NCT02584816] and Clinical Trial Registry of India [CTRI/2015/07/006034].
Assuntos
Anticorpos Antivirais/sangue , Imunogenicidade da Vacina , Vírus Reordenados/imunologia , Vacinas contra Rotavirus/efeitos adversos , Vacinas contra Rotavirus/imunologia , Animais , Bovinos , Estabilidade de Medicamentos , Feminino , Gastroenterite/prevenção & controle , Humanos , Esquemas de Imunização , Lactente , Masculino , Rotavirus/imunologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Vacinação , Vacinas Atenuadas/administração & dosagemRESUMO
BACKGROUND: A newly developed bovine-human reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was tested for its potential effect on the immunogenicity of concomitantly administered EPI vaccines in infants in a randomized controlled study in India. METHODS: In this Phase III, multicenter, open label, randomized, controlled study, three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given to healthy infants at 6, 10, and 14â¯weeks of age. Subjects also received three doses of DTwP-HepB-Hib (diphtheria, tetanus, whole-cell pertussis, hepatitis B, and haemophilus influenzae type b conjugate - pentavalent vaccine) and oral polio vaccine concomitantly at 6, 10, and 14â¯weeks of age and a single dose of inactivated polio vaccine at 14â¯weeks of age. Blood samples were collected four weeks after the final vaccination to assess immune responses to all the vaccines administered. For diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 antibodies, non-interference was to be supported if the lower limit of the two-sided 90% confidence interval (CI) for the seroprotection rate difference for the BRV-PV group minus the Rotarix® group was >10.0%. For pertussis antibodies, non-interference was to be supported if the lower limit of the two-sided 90% CI for the ratio of geometric mean concentrations (GMCs) was >0.5. RESULTS: A total of 1500 infants were randomized to either BRV-PV (1125 infants) or Rotarix® (375 infants), of which 1341 completed the study as per the protocol. More than 97% of subjects achieved seroprotective antibody titres against diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 in both groups. The difference in seroprotection rates between the BRV-PV group and the Rotarix® group for all these antibodies was less than 1%. The ratio of GMCs of anti-pertussis IgG concentrations for the BRV-PV group versus Rotarix® was 1.04 [90% CI: 0.90; 1.19]. CONCLUSION: BRV-PV does not interfere with the immunogenicity of concomitantly administered routine infants vaccines.
Assuntos
Anticorpos Antivirais/sangue , Imunogenicidade da Vacina , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/imunologia , Animais , Bovinos , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/imunologia , Humanos , Esquemas de Imunização , Imunoglobulina G/sangue , Lactente , Masculino , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/imunologia , Vacina Antipólio Oral/administração & dosagem , Vacina Antipólio Oral/imunologia , Vírus Reordenados/imunologia , Vacinas contra Rotavirus/administração & dosagem , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologiaRESUMO
The present study examined the response of zebrafish embryos exposed to different concentrations (10, 20, 30, 40, 50, and 60 mg/L) of monocrotophos under static conditions for 96 h. We found that mortality had occurred within 48 h at all test concentrations, later insignificant mortality was observed. Monocrotophos (MCP) can be rated as moderately toxic to the Zebrafish embryos with a 96-h median lethal concentration (LC50) of 37.44 ± 3.32 mg/L. In contrast, it greatly affected the development of zebrafish embryos by inducing several developmental abnormalities like pericardial edema, altered heart development, spinal and vertebral anomalies in a concentration-dependent manner. A significant percent reduction in length by 9-48% and heart beats by 18-51% was observed in hatchlings exposed to LC10 and LC50 concentrations at 96 h when compared to controls. The process of looping formation of heart at embryonic stage was greatly affected by the LC50 concentration of MCP. The neurotoxic potentiality of MCP was assessed by using a marker enzyme, acetylcholinesterase in both in vitro and in vivo experiments. MCP was found to be the most potent inhibitor of AChE in vitro with an IC50 value of 4.3 × 10(-4) M. The whole-body AChE enzyme activity in vivo was significantly inhibited during the exposure tenure with the maximum inhibition of 62% at 24 h.
Assuntos
Monocrotofós/toxicidade , Praguicidas/toxicidade , Peixe-Zebra/embriologia , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Animais , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/embriologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
The propargyl alcohol on reaction with alkylazides under Sharpless conditions through click chemistry concept gave exclusively 1,4-disubstituted triazoles 2. The compounds 2 were oxidized to aldehydes 3 followed by reaction with aniline resulted Schiff's bases 4. The compounds 4 was further reacted with various aldehydes having α-hydrogen using molecular iodine as a catalyst and obtained 2-alkyl triazole-3-alkyl substituted quinoline derivatives 5. All the final compounds were screened against four human cancer cell lines (THP-1, Colo205, U937 & HeLa) and promising compounds have been identified.
Assuntos
Quinolinas/síntese química , Quinolinas/farmacologia , Triazóis/síntese química , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Quinolinas/química , Triazóis/química , Células U937RESUMO
The sponge Dysidea herbacea was collected from the Mandapam Coast, Tamilnadu, India. Isolated gram quantities of hydroxylated polybrominated diphenyl ether (HO-PBDE) and semi-synthesized a series of new PBDEs derivatives and tested them for antibacterial and cytotoxic activities.
Assuntos
Dysidea/química , Éteres Difenil Halogenados/síntese química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Éteres Difenil Halogenados/farmacologia , Humanos , Estrutura MolecularRESUMO
A simple, highly efficient and stereoselective synthetic route has been developed for synthesis of alpinoid-C (1) and its analogues (2, 3 and 4) from commercially available starting materials by using Wittig olefination, Sharpless asymmetric epoxidation, Grubbs cross metathesis as key steps. All the compounds showed moderate anti-proliferative activity against human leukemia/carcinoma (U-937, THP-1, COLO-205 and HepG2) and mouse melanoma (B16-F10) cancer cell lines. Compounds 3 and 4 are found to be most potent with an IC(50) of 7.53 µM and 32.26 µM on THP-1, 11.12 µM and 7.21 µM on COLO-205 cell lines, respectively.
Assuntos
Alpinia/química , Antineoplásicos Fitogênicos/síntese química , Diarileptanoides/síntese química , Glicoproteínas da Membrana de Plaquetas/antagonistas & inibidores , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diarileptanoides/isolamento & purificação , Diarileptanoides/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Camundongos , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
A series of novel alkyltriazole tagged pyrido[2,3-d]pyrimidine derivatives 5 and 6 was prepared starting from 2,3-active functional pyridine 1via cyclization, propargylation followed by reaction with alkyl or perfluoroalkyl azides under Sharpless conditions. All the compounds 5 and 6 were screened for anticancer activity against three cancer cell lines such as U(937), THP-1 and Colo205. The promising compounds 5b and 5e have been identified.
Assuntos
Antineoplásicos/síntese química , Azidas/química , Sobrevivência Celular/efeitos dos fármacos , Pirimidinas/síntese química , Triazóis/química , Alquilação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Ciclização , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Leucemia Monocítica Aguda/tratamento farmacológico , Leucemia Monocítica Aguda/patologia , Linfoma/tratamento farmacológico , Linfoma/patologia , Pirimidinas/farmacologia , Relação Estrutura-AtividadeRESUMO
BACKGROUND AND THE PURPOSE OF THE STUDY: Lercanidipine hydrochloride (LRDP) is used in the treatment of hypertension because of its selectivity and specificity on the smooth vascular cells. The pharmacokinetic parameters make LRDP a suitable candidate for transdermal delivery. The purpose of the study was to select a suitable formulation for the development of transdermal drug-delivery system (TDDS) of LRDP and to determine the effect of penetration enhancer, limonene on drug permeation METHODS: The matrix type TDDS of LRDP were prepared by solvent evaporation technique. Formulations A1, A2, A3, A4, A5 and A6 were composed of Eudragit RL100 (ERL) and hydroxypropyl methyl cellulose (HPMC) in 1.5:8.5, 3:7, 4:6, 6:4, 7:3 and 8.5:1.5 ratios respectively. All the six formulations carried 10 mg of LRDP/patch area, 8% v/w of d-limonene as a penetration enhancer, 20% v/w of propylene glycol as plasticizer in methanol and dichloromethane as solvent system. The prepared TDDS were evaluated for physicochemical characteristics, in-vitro release, ex-vivo permeation and skin irritation. The ex-vivo permeation studies were carried out across excised rat skin using Franz diffusion cell. RESULTS: All the formulations exhibited satisfactory physicochemical characteristics. Cumulative percentage of the drug released in 24 hrs from the six formulations were 82.0%, 74.9%, 63.2%, 63.5%, 59.8% and 53.5% respectively. Corresponding values for the cumulative amounts of the drug permeated across the rat skin for the above matrix films were 2644.5, 2347.2, 2249.5, 1933.4, 2021.5 and 1663.4 µg/cm(2) respectively. By fitting the data into zero order, first order and Higuchi model, it was concluded that drug release from matrix films followed Higuchi model and the mechanism of the drug release was diffusion mediated. The patches were seemingly free of potentially hazardous skin irritation. CONCLUSIONS: The patches composed of ERL, HPMC (1.5:8.5) with 8% v/w limonene as penetration enhancer may be selected for the development of TDDS of LRDP for potential therapeutic use by using a suitable adhesive layer and backing membrane.
RESUMO
L-Asparaginase is an important component in the treatment of acute lymphoblastic leukemia in children. Its antineoplastic activity toward malignant cells is due to their characteristic nature in slow synthesis of L-asparagine (Asn), which causes starvation for this amino acid, while normal cells are protected from Asn starvation due to their ability to produce this amino acid. The relative selectivity with regard to the metabolism of malignant cells forces to look for novel asparaginase with little glutaminase-producing systems compared to existing enzyme. In this investigation, the role of the extracellular asparaginase enzyme produced by an isolated bacterial strain was studied. Biochemical characterization denoted that this isolated bacterial strain belongs to the Bacillus circulans species. The strain was tested for L-asparaginase production, and it was observed that, under an optimized environment, this isolate produces a maximum of 85 IU ml(-1) within 24-h incubation. This enzyme showed less (60%) glutaminase activity compared to commercial Erwinia sp. L-asparaginase. The partially purified enzyme showed an approximate molecular weight of 140 kDa. This enzyme potency in terms of antineoplastic activity was analyzed against the cancer cells, CCRF-CEM. Flow cytometry experiments indicated an increase of sub-G1 cell population when the cells were treated with L-asparaginase.
Assuntos
Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Asparaginase/biossíntese , Asparaginase/farmacologia , Bacillus/isolamento & purificação , Bacillus/metabolismo , Espaço Extracelular/enzimologia , Antineoplásicos/uso terapêutico , Asparaginase/uso terapêutico , Bacillus/citologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Leucemia/tratamento farmacológicoRESUMO
The euryhaline fish, Oreochromis mossambicus was exposed to sub-lethal concentration (30 microg/L) of profenofos (PF) for 28 days and allowed to recover for 7 days. Responses were evaluated through antioxidant enzyme activities in various tissues of fish. Glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities showed transient increases in gill, viscera and muscle, but decreased in brain. However, catalase (CAT) and glutathione reductase (GR) were inhibited in gill and viscera. Reduced glutathione (GSH) levels were depleted in all the tissues and a significant induction in lipid peroxidation (LPO) was observed. Significant recovery in all the studied parameters was noticed at the end of recuperation period. The enhanced LPO in the present study suggests that reactive oxygen species (ROS)-induced oxidative damage could be one of the main toxic effect of PF. The increased LPO and alterations in the antioxidant defense system can be used as biomarkers in the pesticide-contaminated aquatic streams.
Assuntos
Antioxidantes/metabolismo , Inseticidas/toxicidade , Organotiofosfatos/toxicidade , Tilápia/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Catalase/metabolismo , Brânquias/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Vísceras/metabolismoRESUMO
A total synthesis of yashabushidiol (1a), a linear diarylheptanoid having 1,3- diol system and its analogues has been achieved by alkynylation of 3-hydroxy-5-phenyl pentanal with substituted phenyl acetylenes. All the compounds have shown significant anti-proliferative activity on human leukemia (THP-1, U-937) and melanoma (A-375) cell lines. Compounds 2a and 2b were found to be most potent with an IC(50) of 12.82 microg/mL and 12.62 microg/mL, respectively, on THP-1 leukemia cell line.
Assuntos
Antineoplásicos/síntese química , Heptanos/síntese química , Fenóis/síntese química , Antineoplásicos/química , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Heptanos/toxicidade , Humanos , Fenóis/toxicidadeRESUMO
Bioassay directed fractionation and purification led to the successful isolation of a furano sesquiterpene, Methyl 5-[(1E,5E)-2,6-Dimethyl octa-1,5,7-trienyl] furan-3-carboxylate (MDTFC), a bioactive component from a soft coral, Sinularia kavarittiensis. Its structure was determined by analyzing (1)H, (13)C NMR and FAB-MS. The results show that MDTFC could efficiently and selectively inhibit the proliferation of several human cancer cell lines. Among all the cell lines, THP-1 was found to be most sensitive (IC(50) 29.59 microM), whereas the peripheral blood mononuclear cells were least effected (IC(50) 464.16 microM). The molecular mechanism of MDTFC mediated apoptosis was investigated for the first time. Induction of apoptosis in THP-1 cells was characterized by cell membrane blebbing, chromatin condensation, DNA fragmentation, and decrease in level of pro-caspases 3, 9 and increase in Bax/Bcl-2 ratio. Our results were further strengthened through cleavage of poly (ADP-ribose) polymerase, reduction of mitochondrial membrane potential (Psim) and cytosolic release of cytochrome c, which are key events during apoptosis. Moreover, phosphatidyl serine exposure and appearance of sub-G1 peak also demonstrated cell death, when analyzed by flow cytometry. DNA fragmentation was prevented moderately when pretreated with caspase-9 inhibitor (Z-LEHD-FMK) and largely with caspase-3 inhibitor (Z-DEVD-FMK). In summary, MDTFC mediated apoptosis involves mitochondria-dependent pathway and the present compound of marine origin might have a therapeutic value against human cancer cell lines and especially on leukemia cells.
Assuntos
Antozoários/química , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Leucemia/enzimologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Sesquiterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Colorimetria , Fragmentação do DNA/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Citometria de Fluxo , Humanos , Leucemia/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Propídio/metabolismo , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificaçãoRESUMO
The results of the present research study indicate that the heavy metal accumulation in the marine sponges provide evidence as an excellent bioindicators for monitoring heavy metal pollution between near and offshore environments of Mandapam coast of "Gulf of Mannar (GoM), India". The heavy metal concentrations in sea water and accumulation in the tissues of Haliclona tenuiramosa were analyzed by ICP-MS (inductively coupled plasma-mass spectrometry). The concentrations of metals in the coastal waters of nearshore (< 0.5 km from shore) were always higher than those in the offshore waters (2-5 km away from shore). Likewise, sponges living in the nearshore accumulated greater concentrations of heavy metals (As, Cd, Co, Cu, Fe, Mn and Ni) ranging from 2 to 17 times higher concentration than the sponges located away from the shore. A positive correlation between concentration levels in water and bioaccumulation in tissues was observed. The bioaccumulation of heavy metals in sponge tissue were in order of Fe > Mn > Ni > Cu > As > Co > Cd in both the near and offshore stations. The present results justified that a more comprehensive monitoring of presence of heavy metals in H. tenuiramosa of surrounding GoM, is necessary to help a better mitigation of the problem.
Assuntos
Monitoramento Ambiental/métodos , Haliclona/metabolismo , Metais Pesados/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Cádmio/metabolismo , Cobalto/metabolismo , Cobre/metabolismo , Índia , Ferro/metabolismo , Manganês/metabolismo , Níquel/metabolismoRESUMO
Acute toxicity, morphological alterations and histological effects of an organophosphorus insecticide, profenofos (PFF) to earthworm, Eisenia foetida were evaluated by direct contact through a filter paper. The 24 and 48 h LC(50) was 4.56 and 3.55 microg cm(-2), respectively. Morphological and histological observations showed body ruptures, bloody lesions, and internal excessive formation of glandular cell mass and disintegration of circular and longitudinal muscles, which failed to regulate the internal coelomic pressure, leading to fragmentation in earthworms. Neurotoxic potentiality of PFF was assessed by measuring acetylcholinesterase (AChE). AChE basal K(m) and V(max) values were 0.26 mM and 0.15 micromol min(-1) mg(-1) protein, respectively. PFF alters the in vitro K(m) value, resulting in a competitive type of inhibition. The inhibitory constant K(i) was 2.52x10(-6) M. Morphological alterations and histological effects should be monitored in addition to AChE inhibition to assess OP pesticide contamination in soil ecosystems.
Assuntos
Inseticidas/toxicidade , Oligoquetos/efeitos dos fármacos , Organotiofosfatos/toxicidade , Acetilcolinesterase/metabolismo , Animais , Relação Dose-Resposta a Droga , Dose Letal Mediana , Oligoquetos/enzimologia , Organotiofosfatos/administração & dosagemRESUMO
The acute toxicity and hatching success of four organophosphorus insecticides--acephate (ACEP), chlorpyrifos (CPP), monocrotophos (MCP), and profenofos (PF)--was studied in a short-term bioassay using brine shrimp, Artemia salina. Fifty percent hatchability inhibition concentration and median lethal concentration (LC(50)) values were calculated after probit transformation of the resulting data. Among the insecticides tested, CPP is found to be the most toxic and also to inhibit hatching success of A. salina cysts in a concentration-dependent manner. In addition, the effect of these pesticides on locomotor behavior (swimming speed) and morphologic differences were studied in LC(50)-exposed nauplii after 24 hours. The in vivo effect of these insecticides on acetylcholinesterase (Enzyme commission number (EC 3.1.1.7) activity was also determined in LC(50)-exposed nauplii after 24 hours. Maximum percent decrease in their swimming speed and significant morphologic alterations were noticed in CPP-exposed brine shrimps. The order of toxicity was CPP > PF > MCP > ACEP in all the parameters studied.
Assuntos
Artemia/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Compostos Organofosforados/toxicidade , Praguicidas/toxicidade , Poluentes Químicos da Água/toxicidade , Acetilcolinesterase/metabolismo , Animais , Artemia/embriologia , Artemia/fisiologia , Dose Letal Mediana , Atividade Motora/efeitos dos fármacosRESUMO
The effect of exposure to sublethal concentrations (0.017 mg L(-1), 1/10 of LC50) of the novel organophosphate (OP) insecticide, 2-butenoic acid-3-(diethoxyphosphinothioyl) methyl ester (RPR-II) on biochemical parameters in Oreochromis mossambicus was studied during exposure for 3, 7, 15, 30 and its recovery response after seven days. Acetylcholinesterase (AChE) activity of brain, gill and muscle was inhibited by 67%, 77% and 73% respectively on day-30. The plasma and kidney alanine aminotransferase (AlaAT), and aspartate aminotransferase (AspAT) activity increased, while decreases were observed in gill and liver. Increases in acid phosphatase (AcP), and alkaline phosphatase (AP) activities were observed in plasma, gill, and kidney, and reductions of 20% and 61% in liver AcP and AP, respectively. Depletion of glycogen was observed in all tissues, an indication of typical stress related response of the fish with pesticide. Lactate dehydrogenase (LDH) activity decreased in liver and muscle, indicating tissue damage but a significant increase in LDH activity in gill and brain was observed. Depletion of glutathione (GSH) was observed in all tissues, thereby enhancing lipid peroxidation resulting in cell damage. The induction in hepatic glutathione-S-transferase (GST) levels indicates protection against the toxicity of xenobiotic-induced lipid peroxidation. There was a significant recovery in the above biochemical parameters, in all tissues of fish after a recovery period of seven days. These results revealed that the OP insecticide RPR-II is highly toxic and affects the intermediary metabolism of O. mossambicus.
Assuntos
Inseticidas/toxicidade , Monocrotofós/análogos & derivados , Compostos de Sulfidrila/toxicidade , Tilápia , Acetilcolinesterase/metabolismo , Fosfatase Ácida/metabolismo , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Brânquias/enzimologia , Glutationa/metabolismo , Glicogênio/metabolismo , Rim/enzimologia , Lactato Desidrogenases/metabolismo , Fígado/enzimologia , Monocrotofós/toxicidadeRESUMO
Subacute studies of profenofos on mosquito fish, Gambusia affinis, were carried out for 20 days to assess the locomotor behavior and structural integrity of gill in relation to bioaccumulation and targeted enzyme acetylcholinesterase (AChE; EC 3.1.1.7). The sublethal concentration of 0.13 mg/L (1/5 of LC50) altered locomotor behavior such as distance traveled and swimming speed in exposed fish. This could be due to inhibition in the activity of acetylcholinesterase and deformities in the primary and secondary lamella of gill. The bioaccumulation values indicated that the accumulation of profenofos was highest in viscera followed by head and body. The average bioconcentration factor values are 254.83, 6.18, and 2.52 microg/g for viscera, head, and body. The findings revealed that profenofos is highly toxic even at sublethal concentrations to the mosquito fish, Gambusia affinis.
Assuntos
Ciprinodontiformes/fisiologia , Brânquias/efeitos dos fármacos , Brânquias/patologia , Inseticidas/toxicidade , Atividade Motora/efeitos dos fármacos , Organotiofosfatos/toxicidade , Acetilcolinesterase/metabolismo , Algoritmos , Animais , Brânquias/enzimologia , Inseticidas/farmacocinética , Dose Letal Mediana , Organotiofosfatos/farmacocinética , Distribuição TecidualRESUMO
The acute toxicity of chlorpyrifos and monocrotophos to subterranean termites, Odontotermes obesus (Rambur), has been studied by a paper contact method. The LC50 values for chlorpyrifos and monocrotophos were 0.046 and 0.148 microg cm(-2), respectively. Chlorpyrifos was 3.22-fold more toxic than monocrotophos. The effect of the pesticides on locomotor behaviour (velocity) and head acetylcholinesterase (AChE: EC 3.1.1.7) activity was estimated in LC50-exposed termites at intervals of 4, 8, 12, 16, 20 and 24 h. Chlorpyrifos- and monocrotophos-treated termites showed, respectively, 97 and 88% reduction in locomotor behaviour (velocity) after 24 h. At all time intervals the chlorpyrifos-treated termites exhibited more AChE inhibition and showed greater distorted behaviour than those exposed to monocrotophos. In vitro studies indicated that the I50 value (50% inhibition) for chlorpyrifos against AChE was 8.75 times that of monocrotophos.
Assuntos
Clorpirifos/farmacologia , Inibidores da Colinesterase/farmacologia , Inseticidas/farmacologia , Isópteros , Monocrotofós/farmacologia , Animais , Isópteros/enzimologia , Dose Letal Mediana , Atividade Motora/efeitos dos fármacos , Fatores de TempoRESUMO
Living in an environment that has been altered considerably by anthropogenic activities, fish are often exposed to a multitude of stressors including heavy metals. Copper ions are quite toxic to fish when concentrations are increased in environmental exposures often resulting in physiological, histological, biochemical and enzymatic alterations in fish, which have a great potential to serve as biomarkers. Esomus danricus was chosen as model in the present study and the metabolic rate, gill morphology, total glycogen, total protein, superoxide dismutase and catalase were critically evaluated. The 96h LC50 value was found to be 5.5mg/L (Cu as 1.402 mg/L). Fish groups were separately exposed to lethal (5.5 mg/L) and sub lethal concentrations (0.55 mg/L) of copper sulphate over a period of 96h to examine the subtle effects caused at various functional levels. Controls were also maintained simultaneously. Significant decrease in the metabolic rate (p<0.001) of the fish was observed in both the concentrations studied. Studies employing Automated Video Tracking System revealed gross changes in the architecture of gill morphology like loss, fusion, clubbing of secondary gill lamellae, and detachment of gill rakers following softening of gill shaft in fish under lethal exposures indicating reduced respiratory surface area. Biochemical profiles like total glycogen and total protein in gills and muscle of fish exposed to 5.5 mg/L showed appreciable decrease (p<0.05 to 0.001) from control. Significant inhibition of superoxide dismutase (60.83%), catalase (71.57%) from control was observed in fish exposed to 5.5 mg/L at the end of 96h exposure only. Interestingly, in fish exposed to 0.55 mg/L enzyme activity is not affected except for catalase. Toxic responses evaluated at various functional levels are more pronounced in fish exposed to 5.5 mg/L and these can serve as potential biomarkers for rapid assessment of acute copper toxicity in environmental biomonitoring.