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Biomedical subjects

G Smagghe

Publications and source records attributed to G Smagghe.

32 records · Page 2Linked to original sources
PubMed2002

Comparative toxicity and ecdysone receptor affinity of non-steroidal ecdysone agonists and 20-hydroxyecdysone in Chironomus tentans.

Ecdysone agonists belonging to the bisacylhydrazine class of compounds are a new generation of insecticidal compounds that cause premature lethal molts in susceptible intoxicated insects. While two of the bisacylhydrazines (coded as RH-5992 and RH-2485) are predominantly toxic to lepidopteran pests, RH-5849, which has not been commercialized, has a broader spectrum of toxicity. We have carried out toxicity bioassays with last (4th) instar Chironomus tentans L. larvae, radioligand binding assays using bacterial fusion proteins of C. tentans ecdysone receptor and ultraspiracle (CtEcR, CtUSP), and C. tentans imaginal disc development assays to compare the relative potencies of the three bisacylhydrazine compounds as well as of 20-hydroxyecdysone (20E). In all three assays, the potency of the three bisacylhydrazines was in the order RH-2485>RH-5992>RH-5849. While in toxicity assays 20E was ineffective, most likely due to rapid metabolism, it was more potent than RH-5849 but less so than RH-5992 and RH-2485 in imaginal disc assays. In summary, we compared the potencies of the ecdysone agonists for C. tentans at three levels: whole organism, imaginal discs and the receptor level, and our results indicate that the increased toxicity of the non-steroidal ecdysone agonists for C. tentans has a high correlation to the affinity of these compounds for CtEcR/CtUSP bacterially expressed proteins. Our results, though, do not exclude reasons of metabolic stability of the compounds in C. tentans, which we have not investigated in this report.

Animals↗
PubMed2002

Effect of RH-5992 on adult development in the spruce budworm, Choristoneura fumiferana.

The effect of RH-5992 (tebufenozide), a non-steroidal ecdysone agonist, on adult development of the spruce budworm, Choristoneura fumiferana, was investigated by administering the compound intrahemocoelically to pupae on days 1-6 after pupal ecdysis. At concentrations of 200ng/pupa there was significant mortality but at doses of 50-100ng/pupa, the emerging adults displayed wing deformities which reduced their ability to mate and oviposit. Light microscopy of the pupal wings revealed that there was degeneration of the epithelial cells, reduction in the number of veins, precocious cuticle formation and inhibition of growth of normal wing scales. Injection of RH-5992 into pupae resulted in a dose dependent induction of mRNA for ecdysone-induced transcription factor, Choristoneura hormone receptor 3 (CHR3). These results suggest that the pupae respond to RH-5992 in a manner similar to larvae. However, the effects are not expressed overtly and are camouflaged by the pharmacological effects.

Animals↗
PubMed2002

Insecticidal activity of a nonsteroidal moulting hormone agonist on mosquito larvae and effects on ecdysteroid amounts.

The secondary effects of conventional insecticides on the environment, vertebrates and beneficial organisms have caused a move to the use of more target-specific chemicals such as insect growth regulators. Halofenozide (RH-0345) is a novel nonsteroidal ecdysteroid agonist that induces a precocious and incomplete moult in several insect orders. In the present study, the insecticidal activity of a commercial formulation of halofenozide (23% EC) was evaluated at different concentrations ranging between 8 and 32 micrograms/l. Treatment was made on newly moulted fourth-instar larvae of the mosquito, Culex pipiens (Diptera: Culicidae), and mortality was scored until adult emergence. Results showed that death in the larval stage was relatively important. Moreover, treatment caused a significant reduction in the length of the larval and pupal stage. In a second series of experiments, halofenozide was tested at two doses (LC50 = 12.58 micrograms/l and LC90 = 28.58 micrograms/l) and the ecdysteroid amounts during the fourth instar were evaluated in an enzyme immunoassay. We noted that halofenozide did not shifted the moment of the single larval ecdysteroid peak, but it caused an increase of the titre values. Finally, the compound at the highest concentration was found to increase significantly the cuticle thickness recorded at day 4 following treatment.

Animals↗
PubMed2001

Significance of absorption, oxidation, and binding to toxicity of four ecdysone agonists in multi-resistant cotton leafworm.

Treatment of last-instar larvae of multi-resistant cotton leafworm Spodoptera littoralis with four dibenzoylhydrazines, methoxyfenozide (RH-2485), tebufenozide (RH-5992), halofenozide (RH-0345), and RH-5849, resulted in premature molting leading to death. Methoxyfenozide was the most toxic followed by tebufenozide, halofenozide, and RH-5849. To explain differences in toxicity, especially between multi-resistant and laboratory strains, absorption in the body tissues and oxidative metabolism were tested with 14C-labeled ecdysone agonist and a Lineweaver-Burk assay, respectively. Then to address different compound potencies in multi-resistant strains, the potency of the four ecdysone agonists was measured based on their ability to mimic the natural insect molting hormone, 20-hydroxyecdysone (20E) by inducing evagination in isolated imaginal wing discs. Using monoclonal antibody 9B9, the presence of ecdysteroid receptors in imaginal discs in vitro was confirmed. In parallel, Scatchard plot analysis with whole imaginal wing discs cultured with different concentrations of 3H-labeled ponasterone A indicated no significant difference in affinity and in number of target sites for binding between multi-resistant and susceptible laboratory strains. The four compounds tested caused the effect as agonists of 20E in vitro, and typically the order of their toxicities (LC50s) corresponded with that for evagination-induction with whole imaginal discs.

Absorption↗
PubMed2001

Quantitative structure-activity studies of insect growth regulators: XVIII. Effects of substituents on the aromatic moiety of dibenzoylhydrazines on larvicidal activity against the Colorado potato beetle Leptinotarsa decemlineata.

Larvicidal activity against the Colorado potato beetle Leptinotarsa decemlineata (Say) was measured for a series of N-tert-butyl-dibenzoylhydrazines having various substituents on the benzoyl (A-ring) moiety nearer to the tert-butyl group, with the other benzoyl (B-ring) moiety being unsubstituted. The effects of these substituent on the larvicidal activity were analyzed using classical quantitative structure-activity relationship (QSAR) procedures. The effects of substituents on the A-ring moiety on larvicidal activity were entirely different from those against the lepidopteran rice stem borer Chilo suppressalis (Walker) previously reported. Position-specific steric and hydrophobic effects, as well as certain substitution patterns, were likely to participate in modifying the larvicidal activity. The activity of para-substituted compounds was generally lower than that of un-, ortho- and meta-substituted compounds. Most multi-substituted compounds showed an activity equivalent to or lower than that of the unsubstituted compound. Among 46 compounds tested, the 2-sec-butoxy analogue was most potent against L decemlineata, although this compound had previously been shown to be only weakly active against C suppressalis.

Animals↗
PubMed2001

RH-0345 restored partly the effects induced by KK-42 on reproductive events in mealworms.

In the mealworm, Tenebrio molitor L., KK-42, an imidazole derivative, was found to reduce ovarian ecdysteroid production, while RH-0345, a benzoylhydrazine analogue, has been reported to affect growth and development of mealworm ovaries in a manner similar to 20-hydroxyecdysone. In order to determine whether the reduction of reproduction events is dependent on inhibition of ecdysteroid production by ovaries, RH-0345 (10 micrograms/insect) was applied before or after topical application of KK-42 (10 micrograms/insect) on newly emerged adult females. KK-42 applied alone increased significantly the pre-oviposition period compared to controls. It also significantly delayed egg-laying compared to combined treatments using KK-42 before or after RH-0345. KK-42 applied alone or with and before RH-0345, was found to reduce significantly the duration of oviposition period. Moreover, there was a significant difference in the duration of oviposition period between the two combined treatments. The fecundity was significantly reduced in all treated series compared to controls. In addition, the fecundity recorded in treated series by RH-0345 alone or before KK-42 was significantly higher than in KK-42 treated series. Lastly, the viability of eggs laid was significantly reduced in all treated series compared to controls. Moreover, the combined treatment pronounced the reduction in egg viability. Free ecdysteroids (ecdysone and 20-hydroxyecdysone) in eggs of control and RH-0345 treated females were analyzed by an enzymo-immunoassay using two specific antibodies.

Animals↗
PubMed2001

Comparative action of RH-0345 and pyriproxyfen on molting hormone production and protein analysis in mealworm pupae.

RH-0345 (halofenozide) was found to mimic the action of 20-hydroxyecdysone while pyriproxyfen was presented as a juvenile hormone analogue. In this study, RH-0345 (5, 10 micrograms/pupa) and pyriproxyfen (0.10 and 0.20 microgram/pupa), applied topically on newly ecdysed pupae of Tenebrio molitor, were investigated on ecdysteroid titers and hemolymph protein concentrations. During normal pupal development, the ecdysteroid titer measured using an enzyme immunoassay showed a single peak at day 3. The two compounds did not shifted the moment of the pupal ecdysteroid peak. However, RH-0345 at the highest dose (10 micrograms/pupa) increased the ecdysteroid titres recorded from the second day after topical application while pyriproxyfen decreased this hormonal production. In a second series of experiments, the compounds were evaluated on the protein concentrations in the hemolymph. In control pupae, change in protein concentrations showed two peaks. At a 5 micrograms dose, RH-0345 was found to reduce significantly the value of the first peak and at the highest dose, the first peak was not observed and the values recorded following treatment were significantly lower than in controls. Changes in protein concentrations showed that pyriproxyfen suppressed the second peak and the values recorded were either significantly increased at day 2 and 3, either reduced from day 4.

Animals↗
PubMed1999

Action and pharmacokinetics of a novel insect growth regulator, halofenozide, in adult beetles of aubeonymus mariaefranciscae and leptinotarsa decemlineata

Topical application of halofenozide on adults of the Colorado potato beetle (CPB), Leptinotarsa decemlineata, and Aubeonymus mariaefranciscae (AMF) exhibited its effects in a different way in the two coleopterans. In CPB, the fecundity was strongly affected, whereas the main effect in AMF was a drastic decrease of the progeny survival. The rate of penetration of labeled halofenozide through the cuticle followed a similar pattern in CPB and AMF, whereas the rate of excretion was much more rapid in AMF. The extremely slow excretion of the product in CPB suggested that this fact must contribute to the prolonged action of halofenozide on fecundity at its highest dose of 20 &mgr;g per adult. Retention of halofenozide in the reproductive system of males of AMF and CPB was low, whereas high levels of radioactivity were recovered in females (ovaries + eggs). Comparing females of both coleopterans, CBP retained a higher amount than AMF. Moreover, treated CPB adults showed a rapid cessation of oviposition due to distorted ovaries, detrimental oocyte growth, and loss of oviposition due to the fact that yolk protein synthesis and/or incorporation into eggs was reduced. In AMF, the development of the progeny was strongly affected, and more than 80% of first-instar larvae died after egg hatching in the first 25 days after the treatment, due to premature molting and inhibition of ecdysis. Cross sections of intoxicated first larval instars of AMF originating from adults that were topically treated with halofenozide showed the presence of a double cuticle and these larvae could not shed the old cuticle. Arch. Copyright 1999 Wiley-Liss, Inc.

Journal Article↗
PubMed1999

Cadmium uptake and defense mechanism in insect cells.

The uptake of cadmium and the defense mechanism against this heavy metal were studied in the Aedes albopictus C6/36 cell line. The internalization of cadmium was a very quick process and exhibited saturation kinetics over the metal concentration gradient (1.37 to 131 micromol/L). Cd toxicity and influx were both shown to be temperature dependent. The uptake was not influenced by a 2, 4-dinitrophenol pretreatment but was significantly decreased by the Ca2+ antagonist verapamil. These data suggest that cadmium is readily taken up through mediated transport, not requiring metabolic energy. A considerable amount of the metal passes through the Ca2+ channels, but probably (an)other transporting molecule(s) also play(s) an important role in the uptake process. The remarkable, nonsigmoid viability pattern of Cd-treated cultures suggests that CdCl2 concentrations above 33 micromol/L induce a cellular defense system. This phenomenon went together with increased protein synthesis. We found a major induction of a group consisting of 71-, 75-, and 78-kDa proteins, probably belonging to the HSP70 family, as similar proteins were induced by heat shock. A slight induction of a 120-kDa protein also occurred. At the highest Cd concentrations 98-, 108-, and 110-kDa proteins were induced. These data suggest that heat shock proteins may play an important role in the Aedes cell protection against Cd insult.

2,4-Dinitrophenol↗
PubMed1993

Mortality from lung cancer and cardiovascular diseases among stainless-steel producing workers.

The mortality pattern of workers involved in the production of stainless steel (SS) was studied from 1968 to 1984 in order to investigate a possible risk of lung cancer in relation to exposure to chromium compounds, polycyclic aromatic hydrocarbons, and silica. The role of heat exposure in mortality from cardiovascular diseases also was examined. The cohort was comprised of 4,227 workers. Complete individual job histories were provided by the company (UGINE SA). The smoking habits of 24 percent of the cohort members were known from the interview of workers still active during the data collection. The observed numbers of deaths were compared with the expected ones based on national rates with adjustment for age, sex, and calendar time (standardized mortality ratio, SMR). No significant excesses of lung cancer were observed among workers employed in the manufacture of ferroalloys (SMR = 0.68) and in the melting and casting of SS (SMR = 1.04), whereas a significant excess appeared among SS foundry workers (SMR = 2.29). This excess was higher and remained significant among workers with more than 30 years since first employment in the foundry area (SMR = 3.34). Among subjects exposed to heat, no excess was observed for all cardiovascular diseases or for ischemic heart diseases.

Cardiovascular Diseases↗
PubMed1990

Mortality study among workers producing ferroalloys and stainless steel in France.

A mortality study was carried out among the workers of a plant that had produced ferrochromium and stainless steel, and was still producing stainless steel, in order to determine whether exposure to chromium compounds, to nickel compounds, and to polycyclic aromatic hydrocarbons (PAH) could result in a risk of lung cancer for the exposed workers. The cohort comprised 2269 men whose vital status were recorded between 1 January 1952 and 31 December 1982. The smoking habits of 67% of the cohort members were known from medical records. The observed numbers of deaths were compared with the expected ones based on national rates with adjustment for age, sex, and calendar time. A low mortality, achieving statistical significance, was found from all causes (observed = 137, standardised mortality ratio (SMR) = 0.82) and from benign respiratory diseases (observed = one, SMR = 0.15). With regard to mortality from lung cancer, a non-significant excess appeared in the whole cohort (observed = 12, SMR = 1.40). Among the exposed workers, however, a significant lung cancer excess was found (observed = 11, SMR = 2.04) that contrasted with a low SMR (0.32) in the non-exposed group. This excess is unlikely to be explained by smoking, as the tobacco consumption of these two groups was similar. No trend was observed for mortality from lung cancer either according to time since first exposure, or according to duration of exposure. A nested case-control study clearly suggested that this excess of deaths from lung cancer was attributable to former PAH exposures in the ferrochromium production workshops rather than to exposures in the stainless steel manufacturing areas.

Case-Control Studies↗