Resveratrol alleviates cardiac apoptosis following exposure to fenitrothion by modulating the sirtuin1/c-Jun N-terminal kinases/p53 pathway through pro-oxidant and inflammatory response improvements: In vivo and in silico studies.

Fenitrothion (FNT), a commonly used organophosphate, can cause oxidative damage and apoptosis on various organs. However, the underlying mechanisms for FNT-induced cardiotoxicity did not formally report. Here, we have evaluated the possible ameliorative roles of resveratrol (RSV) against FNT-induced cardiac apoptosis in male rats through the sirtuin1 (SIRT1)/c-Jun N-terminal kinase (c-JNK)/p53 pathway concerning pro-oxidant and inflammatory cytokines. Forty-eight male rats were equally grouped into control, RSV (20 mg/kg), 5-FNT (5 mg/kg), 10-FNT (10 mg/kg), 20-FNT (20 mg/kg), 5-FNT-RSV, 10-FNT-RSV, and 20-FNT-RSV where all doses administrated by gavage for four weeks. The present findings demonstrated that RSV markedly diminished the level of hyperlipidemia and elevation in lactate dehydrogenase (LDH), total creatine kinase (CK-T), and troponin T (TnT) levels following FNT intoxication. Furthermore, RSV significantly reduced FNT-induced cardiac oxidative injury by reducing malondialdehyde (MDA) level and improving the levels of glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and acetylcholinesterase (AchE). Also, the levels of interleukin-1ß (IL1ß,), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly attenuated in the co-treated groups. Moreover, RSV alleviated the histopathological changes promoted by FNT and repaired the transcript levels of SIRT1, c-JNK, and caspase-9/3 along with p53 immunoreactivity. In silico study revealed that the free binding energies of RSV complexes with protein and DNA sequences of SIRT1 were lower than docked complexes of FNT. Therefore, RSV reserved myocardial injury-induced apoptosis following exposure to FNT by modulating the SIRT1/c-JNK/p53 pathway through cellular redox status and inflammatory response improvements.

Walnut Polyphenol Extract Protects against Fenitrothion-Induced Immunotoxicity in Murine Splenic Lymphocytes.

Fenitrothion (FNT), an organophosphate pesticide, exerts an immunotoxic effect on splenocytes. Dietary polyphenol compounds exert antioxidant, anticancer and antihypertensive effects. In this study, we investigated the effect of walnut polyphenol extract (WPE) on FNT-induced immunotoxicity in splenic lymphocytes in vitro. Treatment with WPE significantly increased the proliferation of FNT-exposed splenocytes, as evidenced by increases in the proportions of splenic T lymphocytes (CD3⁺ T cells) and T-cell subsets (CD8⁺ T cells), as well as the secretion of the T-cell-related cytokines interleukin (IL)-2, interferon-γ, IL-4 and granzyme B. These effects were associated with a reduction in oxidative stress, as evidenced by changes in the levels of hydroxyl radical, superoxide dismutase, glutathione peroxidase and malondialdehyde. Moreover, WPE decreased the FNT-induced overexpression of NADPH oxidase 2 and dual oxidase 1 by regulating Toll-like receptor 4 signaling in splenic T-cells. Taken together, these findings suggest that WPE protects against FNT-mediated immunotoxicity and improves immune function by inhibiting oxidative stress.

Postmortem distribution of chlorpyrifos-methyl, fenitrothion, and their metabolites in body fluids and organ tissues of an intoxication case.

We herein report a fatal intoxication case caused by the ingestion of the insecticides chlorpyrifos-methyl (CPFM) and fenitrothion (MEP). A 70-year-old man was found dead in his house and a cup containing a small amount of agricultural chemicals was on the table near his body. External and internal examinations revealed no injuries. In a gas chromatography-mass spectrometry (GC-MS) screening test, CPFM, MEP, and their metabolites, 3,5,6-trichloro-2-pyridinol (TCPY) and 3-methyl-4-nitrophenol (3MNP), respectively, were qualitatively detected in his stomach contents. The concentrations (µg/g) of CPFM, TCPY, MEP, and 3MNP in the extracts of each body fluid and organ tissue were assessed by GC-MS and were as follows: 27.8, 56.2, 17.2, and 2.82 (heart blood); 6.60, 42.9, 1.80, and 2.59 (peripheral blood); 0.0821, 45.9, 2,09, and 102 (urine); 21.4, 26.6, 76.2, and 3.83 (brain (frontal portion)); 16.1, 101, 9.67, and 1.26 (liver); 7.45, 101, 21.4, and 26.1 (right kidney); and 73,500, 9750, 232,000, and 1880 (stomach contents), respectively. Based on these results and autopsy findings, the cause of death was acute fatal intoxication by CPFM and MEP.

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.

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.

Monitoring of five different insecticide resistance status in Turkish house fly Musca domestica L. (Diptera: Muscidae) populations and the relationship between resistance and insecticide usage profile.

OBJECTIVE: The objective of this study is to assess the resistance status and yearly changes involved for house fly populations from six cities in Turkey. METHODS: Field strains of house fly (Musca domestica L. Diptera: Muscidae) were collected in 2004-2006 from cow farms (Antalya, Izmir) and garbage dumps (Adana, Ankara, Istanbul, Sanliurfa) in Turkey. The resistance levels of first and two generation offspring were determined against five insecticides (cypermethrin, cyphenothrin, deltamethrin, permethrin and fenitrothion). RESULTS: While the highest resistance level for pyrethroid was determined for Antalya 2005 strain (851.97 Cypermethrin) and lowest resistance level for Sanliurfa 2004 strain (2.06 Permethrin), the highest fenitrothion resistance was found in Sanliurfa 2004 strain (50.37) and lowest fenitrothion resistance was found in Adana 2004 strain (6.45). CONCLUSION: Our results showed that pyrethroid resistance levels were very high and determined a decreasing trend for Antalya and Istanbul strains and an increasing trend for Adana and Sanliurfa strain for all tested pyrethroid insecticides from 2004 to 2006. Although cypermethrin and cyphenothrin resistance showed a decreasing trend, deltamethrin and permethrin showed an increasing trend for the Izmir strain from 2004 to 2006. The same trend was also determined for the Ankara strain except for permethrin. Fenitrothion resistance was determined to be lower than pyrethroids, but these levels were still high. Flies from cow farms were generally more resistant than those from garbage dumps. Our results also revealed the presence of strong selective pressure on the populations.

Lethal and sublethal effects of fenitrothion and deltamethrin residues on the egg parasitoid Trissolcus grandis (Hymenoptera: Scelionidae).

Effects of fenitrothion and deltamethrin, the most commonly used insecticides in Iran for controlling Eurygaster integriceps Puton (Heteroptera: Scutelleridae), in wheat and barley were assessed on adults and preimaginal stages of egg parasitoid Trissolcus grandis Thompson (Hymenoptera: Scelionidae). Adult parasitoids exposed to field recommended concentrations of the insecticides suffered 100% mortality within 24 h. LC50 values of fenitrothion and deltamethrin for T. grandis were 8.1 and 3.9 microg (AI) /ml, respectively. Both insecticides and the preimaginal stage of exposure had a significant influence on the level of adult emergence from host eggs treated with field recommended rates. Fenitrothion and deltamethrin reduced the emergence rates by 18 and 34.4%, respectively, compared with the control. However, neither insecticide significantly affected the longevity or reproductive capacity of emerged females, or the sex ratio of their progeny. This study revealed that application of these insecticides should be avoided in early season to conserve natural or released populations of T. grandis. Both insecticides seemed to be detrimental to the parasitoid and need to be applied cautiously through season.

Interaction of organophosphate pesticides and related compounds with the androgen receptor.

Identification of several environmental chemicals capable of binding to the androgen receptor (AR) and interfering with its normal function has heightened concern about adverse effects across a broad spectrum of environmental chemicals. We previously demonstrated AR antagonist activity of the organophosphate (OP) pesticide fenitrothion. In this study, we characterized AR activity of analogues of fenitrothion to probe the structural requirements for AR activity among related chemicals. AR activity was measured using HepG2 human hepatoma cells transfected with human AR plus an androgen-responsive luciferase reporter gene, MMTV-luc. AR antagonist activity decreased as alkyl chain length of the phosphoester increased, whereas electron-donating properties of phenyl substituents of the tested compounds did not influence AR activity. Oxon derivatives of fenitrothion, which are more likely to undergo hydrolytic degradation, had no detectable AR antagonist activity. Molecular modeling results suggest that hydrogen-bond energies and the maximum achievable interatomic distance between two terminal H-bond capable sites may influence both the potential to interact with the AR and the nature of the interaction (agonist vs. antagonist) within this series of chemicals. This hypothesis is supported by the results of recent AR homology modeling and crystallographic studies relative to agonist- and antagonist-bound AR complexes. The present results are placed in the context of structure-activity knowledge derived from previous modeling studies as well as studies aimed toward designing nonsteroidal antiandrogen pharmaceuticals. Present results extend understanding of the structural requirements for AR activity to a new class of nonsteroidal, environmental, OP-related chemicals.

Multilevel effects of sublethal fenitrothion exposure in Chironomus riparius Mg. (Diptera, Chironomidae) larvae.

The effects of fenitrothion exposure on fourth-instar Chimnomus riparius larvae were investigated on biochemical, physiological, and population-level parameters. Biochemical effects were investigated through measurements of acetylcholinesterase and cytosolic superoxide dismutase activities. Water content and dry weight of the larvae were used as physiological parameters, and the emergence rate of adults was used as a descriptor of population-level effects. Results showed that the response of most parameters exhibited a concentration-dependent relationship. Although biochemical parameters proved to be very sensitive, no direct relation was observed with effects at a higher level of biological organization. Perturbations of osmoregulation, as reflected by changes in water content of the larvae, were more directly related with emergence failure. This study demonstrates that the use of several biological parameters can provide complementary information about the effects of chemical exposure. Therefore, use of a multilevel approach in C. riparius seems to be a promising way to diagnose environmental quality.

Changes in mutagenicity during biodegradation of fenitrothion.

In order to investigate changes in the mutagenicity of fenitrothion during its biodegradation in solution, measurements were conducted at intervals in batch cultures incubated under anaerobic or aerobic conditions. Fenitrothion-degrading bacteria were obtained from a green onion field on the west side of Gifu University, Japan. Fenitrothion was almost completely decomposed by day 12 under both types of incubation condition. The indirect mutagenicity of the solution to strains YG1029 and YG1042, however, increased markedly during anaerobic biodegradation. The increase in mutagenicity was partially due to amino-fenitrothion, a metabolite formed during anaerobic biodegradation of fenitrothion.

Effects of the organophosphorus insecticide fenitrothion on growth in five freshwater species of phytoplankton.

The acute toxicity of the insecticide fenitrothion was measured using four freshwater algae (Chlorella saccharophila, Chlorella vulgaris, Scenedesmus acutus, and Scenedesmus subspicatus) and one cyanobacteria (Pseudanabaena galeata). Insecticide concentrations eliciting 50% growth reduction over 96 hr (EC50) ranged from 0.84 to 11.9 mg/L. Fenitrothion was more toxic than other pesticides studied with the same algal species such as chlorsulfuron, molinate, and pyridaphenthion. The transformation of effective concentrations of fenitrothion and other pesticides obtained from toxicity measurements into percent of the saturation level in water is used as a first evaluation of potential hazard to aquatic systems. The insecticides fenitrothion and pyridaphenthion were less hazardous than the herbicides atrazine, benthiocarb, cinosulfuron, chlorsulfuron, methyl-bensulfuron, and molinate. The two species of Chlorella and the cyanobacterium Pseudanabaena were more tolerant to fenitrothion than the two species of Scenedesmus.

Biological indicators for the assessment of human exposure to organophosphorous compounds.

UNLABELLED: The aim of the present study is to review selected biological effects of organophosphorous compounds used as pesticides and to discuss their significance in terms of occupational exposure. The results of a long-term study of the red cells and plasma ChE in group of workers engaged in the production of pesticides are also presented. Cholinesterase activity in plasma and red blood cells was determined spectrophotometrically by the Ellman modified method. Occupational exposure to pesticides was analysed by the Durham and Wolf method. CONCLUSIONS: 1. Cholinesterase activity in blood serum of the workers employed at the production of organophosphorous compounds is statistically significantly lower, compared to the control group and the lower accepted standard limit. 2. Cholinesterase activity in plasma seems to be a more sensitive indicator of exposure, compared to the activity of enzyme contained in erythrocytes after a long-lasting exposure to low levels of organophosphorous compounds. 3. Changes in cholinesterase activity according to the level of exposure show a better correlation if the exposure is expressed in % of the toxic dose/day than in mg/day. Toxicological properties of organophosphorous compounds are of the great importance for this correlation.

Chemical management of forest pest epidemics: a case study.

The management of insect epidemics in large tracts of forest is difficult given the climatic conditions encountered, the topography of the forested land, the nature of the forest, the types of chemical and/or biological insecticides registered for use, and the technologies available for insecticide application. Since 1952, the province of New Brunswick, Canada, has been heavily involved in attempting to control an epidemic of the eastern spruce budworm (Choristoneura fumiferana. Clemens) that has ravaged the coniferous softwoods of eastern Canada and the United States. Of the available options, the provincial government chose to develop an aerial spraying program, eventually selecting two chemical insecticides (fenitrothion and aminocarb) and one biological control agent (Bacillus thuringiensis). Concerns about possible impacts on human health led to extensive studies of the toxicology of these insecticides, the technology of aerial spraying, the development of less hazardous formulations, and the quantitation of off-target drift of aerosolized insecticides. These studies culminated in improvements in pesticide application and the establishment of regulations on safety or buffer zones around human habitation for certain types of aircraft applying different formulations of the insecticides.

Ultralow volume application of organophosphate concentrate in grain terminals: a new occupational health hazard.

The introduction of ultralow volume (ULV) application of the organophosphate pesticide Fenitrothion in grain terminals presents a risk to workers of skin contact with concentrate. Blood testing, by the Ellman method, of a group of five grain terminal workers working on grain treatment showed a lowering of mean red blood cell cholinesterase (RBC ChE) activity to 23 units/gm Hb (normal value 28-40) with a range of 16-29. The probable cause was identified as percutaneous absorption of Fenitrothion concentrate by workers using ungloved hands to clean blocked drip feed nozzles. Modification of work practices was followed by a rise of mean RBC ChE to 33.6 units/gm Hb (range 32-36) during the following grain treatment season. RBC ChE activity measured during the intervening winter season--that is, a non-exposure period--showed a mean of 33.3 units/gm Hb (range 23-40).