Ameliorative Effects of Honey, Propolis, Pollen, and Royal Jelly Mixture against Chronic Toxicity of Sumithion Insecticide in White Albino Rats.

Sumithion (Fenitrothion) (SUM) is an organophosphorus insecticide used to combat a wide variety of plant pests. Exposure to SUM causes significant toxicity to the brain, liver, kidney, and reproductive organs through, for example, binding to DNA, and it induces DNA damage, which ends with oxidative stress. Therefore, the present study aimed to examine the protective role of bee products: a mixture of honey, propolis, palm pollen, and royal jelly (HPPJ) against SUM-induced toxicity. Twenty-four male albino rats (Rattus norvegicus) were classified into four groups, each containing six rats: control (corn oil), SUM (85 mg/kg; 1/20 LD50), HPPJ, and SUM + HPPJ once daily for 28 consecutive days. Blood samples were gently collected in sterilized ethylenediaminetetraacetic acid (EDTA) tubes for blood picture analyses and tubes without anticoagulant for serum isolation. Serum was used for assays of enzymatic and biochemical characteristics. The results revealed that SUM increased the weights of the liver, kidney, and brain as well as the enzymatic activity of glutathione peroxidase (GP), serum superoxide dismutase (SOD), and glutathione-S-transferase (GST). Additionally, SUM significantly increased the activity of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and γ-glutamyltransferase (γ-GT) and glucose, uric acid, and creatinine contents, while decreasing the acetylcholine esterase (AChE) activity and total lipids and total protein content. Furthermore, because of the inclusion of phenolic, flavonoids, terpenoids, and sugars, the HPPJ mixture counteracted the hematological, renal, and hepatic toxicity of SUM exposure.

Pesticide-contaminated feeds in integrated grass carp aquaculture: toxicology and bioaccumulation.

Effects of dissolved pesticides on fish are widely described, but little is known about effects of pesticide-contaminated feeds taken up orally by fish. In integrated farms, pesticides used on crops may affect grass carp that feed on plants from these fields. In northern Vietnam, grass carp suffer seasonal mass mortalities which may be caused by pesticide-contaminated plants. To test effects of pesticide-contaminated feeds on health and bioaccumulation in grass carp, a net-cage trial was conducted with 5 differently contaminated grasses. Grass was spiked with 2 levels of trichlorfon/fenitrothion and fenobucarb. Unspiked grass was used as a control. Fish were fed at a daily rate of 20% of body mass for 10 d. The concentrations of fenitrothion and fenobucarb in pond water increased over time. Effects on fish mortality were not found. Fenobucarb in feed showed the strongest effects on fish by lowering feed uptake, deforming the liver, increasing blood glucose and reducing cholinesterase activity in blood serum, depending on feed uptake. Fenobucarb showed increased levels in flesh in all treatments, suggesting bio-concentration. Trichlorfon and fenitrothion did not significantly affect feed uptake but showed concentration-dependent reduction of cholinesterase activity and liver changes. Fenitrothion showed bioaccumulation in flesh which was dependant on feed uptake, whereas trichlorfon was only detected in very low concentrations in all treatments. Pesticide levels were all detected below the maximum residue levels in food. The pesticide-contaminated feeds tested did not cause mortality in grass carp but were associated with negative physiological responses and may increase susceptibility to diseases.

Alteration of carbohydrates metabolism and midgut glucose absorption in Gromphadorhina portentosa after subchronic exposure to imidacloprid and fenitrothion.

This study was undertaken to test the hypothesis that following exposure to insecticides, changes take place in the metabolism of carbohydrates and absorption in the midgut of insects. The Madagascar hissing cockroach (Gromphadorhina portentosa) was chosen for the experiment as a model organism, due to it being easy to breed and its relatively large alimentary tract, which was important when preparing the microperfusion midgut bioassay. In each group of cockroaches treated with imidacloprid and fenitrothion, absorption of glucose, expressed as the area under the curve (AUC), was elevated compared to the control group. Glucose in the hemolymph of the examined insects was present in a vestigial amount, often below the threshold of determination, so the determinable carbohydrate indices were: hemolymph trehalose concentration and fat body glycogen content. The level of trehalose found in the hemolymph of insects when exposed to fenitrothion, and irrespective of the level of concentration mixed into food, were significantly lower when comparing to the control samples. Imidacloprid acted analogically with one exception at the concentration of 10 mg·kg(-1) dry food where trehalose concentration did not differ from the control values. Coupling with fat body glycogen concentration was less visible and appeared only at the concentrations of 5 and 10 mg imidacloprid·kg(-1) dry food. As described in this study changes in the sugar distribution and midgut glucose absorption indicate that insects cover the increased energy needs induced by insecticides; also at the gastrointestinal tract level. The result indicates that the midgut glucose absorption parameters could be considered as a non-specific biomarker of insecticide toxicity.

Amelioration of fenitrothion induced oxidative DNA damage and inactivation of caspase-3 in the brain and spleen tissues of male rats by N-acetylcysteine.

N-acetylcysteine (NAC) has largely been used as an effective chemo- protective agent owing to their beneficial effect in restoring several physiological parameters and relieving oxidative stress. Interestingly, it has been suggested that NAC mechanisms of action extend beyond being a precursor to the antioxidant glutathione and that they may involve several neurotropic and inflammatory pathways. Exposure to fenitrothion, an organophosphorus insecticide, promotes oxidative stress and induces several deleterious changes in the immune response and various tissues including cerebrum and spleen. The main objective of our study was to investigate ameliorative efficacy of N-acetylcysteine for immunological and neurological alterations and oxidative DNA damage induced by fenitrothion toxicity in cerebrum and spleen tissues of male rats. Our results revealed that oral exposure to fenitrothion for 30 days caused a reduction in the erythrocyte count in addition to leukocytosis, lymphocytosis, and neutrophilia. Also, this route of administration increased the serum levels of LDH, TNF-α, and IL-2 with reduction in serum immunoglobulins (IgG & IgM) concentrations. Furthermore, a significant downregulation in the antioxidant markers (GSH & SOD) with an elevation of free radical (MDA) levels were noticed. Regarding the brain, fenitrothion administration inhibited AchE activity and increased brain GABA, serotonin and dopamine levels. Moreover, it induced an elevation in oxidative DNA damage indicated by 8-hydroxy 2-deoxyguanosine (8OH2dG) and mRNA expression of pro-apoptotic genes, including Bax, and p53, but Bcl-2 expression was reduced. N-acetylcysteine co-treatment restored the normal physiological tone in most of these parameters. Immunostaining for GFAP and Caspase-3 markers in the brain and spleen tissues were increased respectively. In conclusion, N-acetylcysteine supplementation has an ameliorative effect against immunotoxic, neurotoxic and oxidative DNA damage induced by fenitrothion exposure.

The ameliorating effects of selenium and vitamin C against fenitrothion-induced blood toxicity in Wistar rats.

Fenitrothion is widely used organophosphate pesticide in agriculture and health programs, but besides, it causes several toxic effects. The present study was designed to evaluate the possible protective effects of selenium (0.5mg/kg b.w.) and vitamin C (100mg/kg b.w) on altered haematological, biochemical and oxidative stress parameters in the blood of rats orally treated with fenitrothion (20mg/kg b.w) for 30days. Fenitrothion caused changes in body weight, food and water intake, and some haematological and biochemical parameters. Fenitrothion altered the glutathione redox status (GSH and GSSG) and decreased activity of antioxidant enzymes (GSH-Px, GST, SOD and CAT), leading to a lipid peroxidation. Selenium and vitamin C, by improving the activity of antioxidants, reduced oxidative stress and a lipid peroxidation, maintaining the values of examined parameters to optimal levels. Therefore, selenium and vitamin C could be useful in providing protection of exposed non-target organisms including people from fenitrothion.

EFFICACY OF THREE INSECTICIDES ON RAT FLEA (XENOPSYLLA CHEOPIS) INFESTING RODENTS IN GIZA GOVERNORATE, EGYPT.

The extensive use of insecticides in public health and agriculture sectors is the main reason for development of resistance in fleas associated in domestic rodents. The present work was planned to investigate the insecticidal efficacy of Lambda-cyhalothrin, Chlorpyrifos and Fenitrothion against rat flea (Xenopsylla cheopis) infesting rodent species in Giza Governorate, Egypt. The lethal concentration Lc50 and Lc90 of population percent were obtained from the established regression log concentrate-response lines. Data indicated that the values of lethal concentration (Lc50) were 0.293, 1.725 & 2.328% for Lambda-cyhalothrin, chlorpyrifos and Fenitrothion, respectively. The values of lethal concentration (Lc90) were 0.467, 2.839 & 5.197% for Lambda-cyhalothrin, chlorpyrifos and Fenitrothion, respectively.

Evaluation of urinary corticosterone as a biomarker of stress in rats using fenitrothion as a chemical stressor.

Regulatory guidelines for pharmaceutical toxicity studies recommend using one dose near the maximum tolerated. At that level significant toxicities may occur, leading to systemic stress and secondary immune suppression which can be difficult to differentiate from a primary drug effect. Therefore, there is a need for a biomarker of stress applicable to toxicity studies. This study evaluated urinary corticosterone as a biomarker, using as a pharmacologic stressor fenitrothion, which was previously shown not to cause primary immune suppression. Rats were administered fenitrothion orally at 20 and 30 mg/kg daily for 2 or 8 days, with matched vehicle controls (n = 6/group). Urine was collected for 6 and 24 h, before treatment and on Day 2 and Day 8. Urine was assayed for corticosterone, separately for the first 6 h of collection and for the whole 24 h sample. Animals were euthanized on Day 3 or Day 9 and lymphoid tissue samples were collected, weighed and examined histologically. Treated rats showed neurologic signs following treatment. Findings also included time- and dose-dependent decreases in body weight and spleen and thymus weight decreases supra-proportional to body weight on Day 9. Histologic changes were mild at a dose of 20 mg/kg, but significant at 30 mg/kg, consisting of lymphocytolysis at Day 3 and lymphoid depletion at Day 9. Urine corticosterone levels were increased on Day 2 and Day 8, in the 6-h samples, but not the 24-h ones, at both dose levels. Based on the results, urine corticosterone appears to be a sensitive biomarker of systemic stress caused by fenitrothion. Other chemical stressors should be evaluated in a similar manner in order to fully validate urine corticosterone measurement as a stress biomarker.

Fenitrothion: toxicokinetics and toxicologic evaluation in human volunteers.

An unblinded crossover study of fenitrothion 0.18 mg/kg/day [36 times the acceptable daily intake (ADI)] and 0.36 mg/kg/day (72 X ADI) administered as two daily divided doses for 4 days in 12 human volunteers was designed and undertaken after results from a pilot study. On days 1 and 4, blood and urine samples were collected for analysis of fenitrothion and its major metabolites, as well as plasma and red blood cell cholinesterase activities, and biochemistry and hematology examination. Pharmacokinetic parameters could only be determined at the higher dosage, as there were insufficient measurable fenitrothion blood levels at the lower dosage and the fenitrooxone metabolite could not be measured. There was a wide range of interindividual variability in blood levels, with peak levels achieved between 1 and 4 hr and a half-life for fenitrothion of 0.8-4.5 hr. Although based on the half-life, steady-state levels should have been achieved; the area under the curve (AUC)(0-12 hr) to AUC(0-(infinity) )ratio of 1:3 suggested accumulation of fenitrothion. There was no significant change in plasma or red blood cell cholinesterase activity with repeated dosing at either dosage level of fenitrothion, and there were no significant abnormalities detected on biochemical or hematologic monitoring.

Effects of in utero exposure to the organophosphate insecticide fenitrothion on androgen-dependent reproductive development in the Crl:CD(SD)BR rat.

Fenitrothion [0,0-dimethyl-O-(4-nitro-m-tolyl) phosphorothioate] is an organophosphate insecticide that has been shown to have antiandrogenic activity using in vitro and in vivo screening assays. Studies were performed to evaluate the ability of fenitrothion to disrupt androgen-dependent sexual differentiation in the male rat. Pregnant Crl:CD(SD)BR rats were administered fenitrothion by gavage at 0, 5, 10, 15, 20, or 25 mg/kg/day ( n = 6-11/group) from gestation day (GD) 12 to 21. Maternal toxicity was observed in the dams treated with 20 and 25 mg fenitrothion/kg/day based on muscle tremors and decreases in body weight gain from GD 12 to 21. Fetal death was increased in the 20 and 25 mg/kg/day exposure groups, as evidenced by a decrease in the proportion of pups born alive. Androgen-mediated development of the reproductive tract was altered in male offspring exposed in utero to maternally toxic levels of fenitrothion (25 mg/kg/day), as evidenced by reduction in anogenital distance on postnatal day (PND) 1 and retention of areolae on PND 13. However, these effects were only transient, and there were no indications of abnormal phenotypes or development of androgen-dependent tissues on PND 100. At the dose levels evaluated in this study, fenitrothion was only weakly antiandrogenic in vivo compared with other androgen receptor antagonists such as flutamide, linuron, and vinclozolin. Based on observed fetotoxicity at 20 mg/kg/day, the lowest observed adverse effect level (LOAEL) for developmental effects can be lowered from 25 to 20 mg/kg/day.

A safety study on rat's eye after 13-week oral administration with fenitrothion.

The potential of ocular toxicity of fenitrothion (O,O-dimethyl O-4-nitrom-tolyl phosphorothioate) was assessed in Sprague-Dawley (Crj:CD) rats of both sexes receiving a diet containing the test compound at concentrations of 0, 2.5, 5, 10, or 30 ppm for 13 weeks. The animals were observed daily for clinical signs and their body weights and food consumption were measured weekly during the study. At termination of treatment, surviving animals were subjected to ophthalmoscopy, electroretinography, and biochemical analyses of plasma, erythrocyte, and brain cholinesterase (ChE). Histopathological examinations of ocular tissues were performed on all animals by light microscopy and on two animals/sex/dose by electron microscopy. There were no treatment-related changes in clinical signs, body weights, and food consumption. A significant inhibition of ChE activity was observed in males (plasma and erythrocyte ChE) and females (plasma, erythrocyte, and brain ChE) at 30 ppm and in females (plasma ChE) at 10 ppm. Ophthalmological and histopathological examinations revealed neither functional nor morphological alterations in the visual system at any dose level. Under the conditions of the present study, there was no evidence of ocular toxicity of fenitrothion for male and female rats at dose levels up to 30 ppm (1.70 mg/kg/day for males and 1.96 mg/kg/day for females) where distinct inhibition of ChE activity was observed.

Laboratory evaluation of fenitrothion microcapsules as a new residual spraying formulation for mosquito control.

Physicochemical and insecticidal properties of fenitrothion microcapsule (MC) as a new residual spraying formulation for mosquito control were studied. The wall staining after treatment with MC at the rate of 1-2 g AI/m2 was not noticeable as compared with that of wettable powder (WP). Covering rate with MC on a vertical wall was almost the same as WP and emulsifiable concentrate (EC) when the wall material was absorptive plywood and mud, and was relatively higher than WP and EC when the wall material was nonabsorptive overlaid plywood. Residual efficacy of MC at the rate of 1 g/m2 was almost equivalent or superior to that of WP at the rate of 2 g/m2. Fenitrothion MC also has had an "airborne" effect, which is sort of a vapor killing effect of insecticides under high vapor pressure. This suggested a difference in mode of action in mosquitoes from that for cockroach control.

Genetic and cytogenetic effects of Fenitrothion.

Male mice (Q strain) were injected intraperitoneally with a high dose (i.e., 1 g/kg) of the organophosphorus insecticide Fenitrothion. No increase in the percentage of chromosome aberrations was observed in bone marrow cells and spermatogonia. A dominant lethal mutation assay did not show any enhancement of fetal mortality before or after implantation.

Antifeeding effect of several insecticidal formulations against Ctenocephalides felis on cats.

Evaluation of insecticidal activity of flea products is generally based on counting live fleas in the animal's coat 24 and 48 hours following artificial infestation. This approach, however, does not allow to specify whether the fleas have had the opportunity to bite and take a bloodmeal prior to their death. To address this question, 30 cats were alloted to six groups of five animals. Each cat was housed in a separate cage. At Day 0, each group of cats received a single treatment as follows: Group 1: spot-on application of imidacloprid: cats < 4 kg: 40 mg/cat, cats > or = 4 kg: 80 mg/cat (Advantage). Group 2: spot-on application of fipronil: 50 mg/cat (Frontline spot-on). Group 3: spray application of fipronil: 7.5 mg/kg b.w. (Frontline spray). Group 4: foam application of permethrin 40/60: 50 mg/kg b.w. (Defencat). Group 5: aerosol spray application of dichlorvos + fenitrothion: one second/kg b.w. (NuvanTop). Group 6: control group: cats were left untreated. One hour after treatment, each cat was infested with 50 unengorged young adult fleas, Ctenocephalides felis, deposited along the dorsal midline. One hour later, each cat was carefully combed using a fine-toothed comb (13 teeth/cm). Collected fleas were swatted to deteci blood in their abdomen. To the manufacturers respective product use instructions and efficacy claims, reeinfestations were made at Days 3, 7, 14 in all groups; at Days 21 and 30 in Groups 1, 2, 4, 6; at Days 35 and 42 in Groups 3 and 6. The cats were combed one hour after each reinfestation. The results indicate that the topical application of imidacloprid or fipronil does not prevent fleas from biting and feeding within the first hour after infestation prior to being killed while the topical application of dichlorvos/fenitrothion and permethrin let to a better than 80% decrease of the number of engorged fleas for three and seven days post treatment, respectively.

Changes in brain acetylcholine of rats after dermal application of fenitrothion (Sumithion).

Fenitrothion (Sumithion), and organophosphorous insectide, was applied dermally to rats. Cholinesterase activity was measured in blood and brain. The concentration of the pesticide in blood plasma and acetylcholine in brain were estimated at different intervals. The maximum concentration of Fenitrothion in the plasma was found at 4 hrs while significantly elevated levels of acetylcholine were present in the brain till 24 hrs. The results suggest that the compound was readily absorbed by dermal route to produce inhibition of cholinesterase and a consequent persistent increase in brain acetylcholine.

Embryonic toxicity of insecticide Sumithion 50 EC and herbicide Fusilade S in pheasants after individual or combined administration.

The purpose of this work was to determine the individual and combined effects of insecticide Sumithion 50 EC (50% fenitrothion) and herbicide Fusilade S (12.5% fluazifop-P-butyl) on the development of pheasant embryos. Eggs were treated by injection of various concentrations of pesticides into the air space on day 12 of incubation. Pathological examination of embryos was carried out on day 23 of the hatching period. Mortality rate, body weight data and morphological alterations were evaluated after the macroscopic examination. The skeletal staining method was used to detect deformities. The two pesticides used in combination moderated the toxic/teratogenic effects of individual treatment.

[Effects of repeated inhalation-exposure to fenitrothion powder on blood cholinesterase activity in rats].

Effects of repeated exposure to Fenitrothion (Sumithion) powder on erythrocyte membrane acetylcholinesterase (AChE) and plasma cholinesterase (PChE) were studied. Rats (Wistar, male) were exposed to fenitrothion powder for 2 hrs/day, 5 days/week for up to 3 months. The suppression of AChE and PChE increased as the exposure period and exposure concentration increased, although no suppression of AChE was found after a single 4-hr exposure. The persistence of AChE inhibition after the termination of exposure increased with the increase of the exposure period and was longer than that of PChE. Therefore, the AChE activity seems to be useful in examining the response to the repeated exposure to fenitrothion powder.

Fenitrothion alters sperm characteristics in rats: ameliorating effects of palm oil tocotrienol-rich fraction.

Exposure to organophosphate insecticides such as fenitrothion (FNT) in agriculture and public health has been reported to affect sperm quality. Antioxidants may have a potential to reduce spermatotoxic effects induced by organophosphate. The present study was carried out to evaluate the effects of palm oil tocotrienol-rich fraction (TRF) in reducing the detrimental effects occurring in spermatozoa of FNT-treated rats. Adult male Sprague-Dawley rats were divided into four equal groups: a control group and groups of rats treated orally with palm oil TRF (200 mg/kg), FNT (20 mg/kg) and palm oil TRF (200 mg/kg) combined with FNT (20 mg/kg). The sperm characteristics, DNA damage, superoxide dismutase (SOD) activity, and levels of reduced glutathione (GSH), malondialdehyde (MDA), and protein carbonyl (PC) were evaluated. Supplementation with TRF attenuated the detrimental effects of FNT by significantly increasing the sperm counts, motility, and viability and decreased the abnormal sperm morphology. The SOD activity and GSH level were significantly increased, whereas the MDA and PC levels were significantly decreased in the TRF+FNT group compared with the rats receiving FNT alone. TRF significantly decreased the DNA damage in the sperm of FNT-treated rats. A significant correlation between abnormal sperm morphology and DNA damage was found in all groups. TRF showed the potential to reduce the detrimental effects occurring in spermatozoa of FNT-treated rats.

Acute oral toxicity of the organophosphorus pesticide fenitrothion to fat-tailed and stripe-faced dunnarts and its relevance for pesticide risk assessments in Australia.

The scarcity of information on the effects of pesticides on native Australian vertebrates constrains the development of biologically relevant risk assessments in Australia for the registration of pesticides. The concern that endemically old and unique Australian vertebrate fauna might display high sensitivity to pesticides used for locust control provoked examination of the acute oral toxicity of the organophosphorus pesticide fenitrothion for the fat-tailed dunnart, Sminthopsis crassicaudata (Gould 1844), and the stripe-faced dunnart, S. macroura (Gould 1845). By using the up-and-down method for determining acute oral toxicity, S. crassicaudata and S. macroura were found to have estimated median lethal doses (LD50s) of 129 mg/kg (95% confidence interval [CI] = 74.2-159.0) and 97 mg/kg (95% CI = 88.3-120.0), respectively. These values are 10 to 14 times lower than the reported LD50 values for a similar-sized eutherian mammal, Mus musculus (L. 1758; LD50 = 1,100-1,400 mg/kg) and lower than all other reported mammalian LD50 values. Such wide interspecific variation in sensitivity to fenitrothion may be a consequence of underlying differences in the metabolic pathway for fenitrothion detoxification in mammals and a possible explanation for the increased toxicity of fenitrothion to dunnarts, compared with other mammals, is proposed. The unexpectedly high sensitivity of these Australian marsupials to fenitrothion emphasises the importance of adequately evaluating the risks of pesticides to endemic Australian fauna.