Citrus reticulata peel extract mitigates oxidative stress and liver injury induced by abamectin in rats.

The prevalent use of abamectin (ABM) has latterly raised safety attention as it has different toxicities to non-target living organisms. Citrus fruits are widely renowned for their nutritional and health-promoting qualities, and their peels are full of phenolic constituents. The purpose of the current study was to evaluate the modulatory effectiveness of Citrus reticulata peel extract (CPE) against abamectin-induced hepatotoxicity and oxidative injury. Rats were distributed into 4 groups as follows: control, CPE (400 mg/kg bw orally for 14 days), ABM (2 mg/kg bw for 5 days), and CPE + ABM at the doses mentioned above. Results revealed that GC-MS analysis of CPE has 19 identified components with significant total phenolic and flavonoid contents. Treatment with ABM in rats displayed significant variations in enzymatic and non-enzymatic antioxidants, oxidative stress markers (MDA, H2O2, PCC), liver and kidney function biomarkers, hematological parameters, lipids, and protein profile as well as histopathological abnormalities, inflammation and apoptosis (TNF-α, Caspase-3, NF-κB, and Bcl-2 genes) in rats' liver. Supplementation of CPE solo dramatically improved the antioxidant state and reduced oxidative stress. C. reticulata peel extract pretreatment alleviated ABM toxicity by modulating most of the tested parameters compared to the ABM group. Conclusively, CPE had potent antioxidant activity and could be used in the modulation of ABM hepatotoxicity presumably due to its antioxidant, anti-inflammatory, and gene-regulating capabilities.

Non-target toxic effects of avermectin on carp spleen involve oxidative stress, inflammation, and apoptosis.

Avermectin is one of the most widely used pesticides, but its toxicity to non-target organisms, especially aquatic organisms, has been ignored. Therefore, an acute spleen injury model of avermectin in carp was established to assess the non-target toxicity of avermectin to carp. In this study, 3.005 µg/L and 12.02 µg/L were set as the low and high dose groups of avermectin, respectively, and a four days acute exposure experiment was conducted. Pathological structure observation showed that avermectin damaged spleen tissue structure and produced inflammatory cell infiltration. Biochemical analysis showed that avermectin significantly reduced the activities of antioxidant enzymes CAT, SOD, and GSH-px, but increased the content of MDA, a marker of oxidative damage. Avermectin exposure also significantly increased the transcription levels of inflammatory cytokines such as IL-1ß, IL-6, TNF-α, and INOS, and also significantly enhanced the activity of the inflammatory mediator iNOS, but suppressed the transcription levels of anti-inflammatory factors TGF-ß1 and IL-10. In addition, TUNEL detected that the apoptosis rate increased significantly with the increase of avermectin dosage, and the transcription levels of apoptosis-related genes BAX, P53, and Caspase 3/9 also increased in a dose-dependent manner. This study is preliminary evidence that avermectin induces spleen injury in carp through oxidative stress, inflammation, and apoptosis, which has important implications for subsequent studies on the effects of avermectin on non-target organisms.

Neuroprotective effect of hesperidin against emamectin benzoate-induced neurobehavioral toxicity in rats.

Emamectin Benzoate (EMB) is an avermectin insecticide widely used in agriculture and veterinary medicine. Hesperidin (HSP) is a flavanone glycoside predominantly found in citrus fruits and has various beneficial health effects. The current research was conducted to study the neurobehavioral toxic effects of EMB in rats and also to evaluate the protective effect of HSP against these toxic effects. Sixty Sprague-Dawley rats were randomly divided into 4 equal groups: control group, EMB group, HSP group, and EMB + HSP group. EMB (8.8. mg/kg) and/or HSP (100 mg/kg) were administered daily by gavage for 8 weeks. The behavioral assessment demonstrated the adverse effects of EMB on the behavioral, motor, and cognitive brain functions. Exposure to EMB also decreased the activity of antioxidants (catalase and reduced glutathione) and increased the malondialdehyde level in nervous tissue. Moreover, EMB increased the level of inflammatory cytokines (tumor necrosis factor-α and interleukin-1ß) and decreased brain-derived neurotrophic factor (BDNF) levels in rats' brains. On the other hand, concurrent administration of HSP ameliorated the toxic effects of EMB as indicated by improvements in neural functions and reduction of oxidative stress and inflammation. The study concluded that exposure to EMB induces toxic effects in the brain of rats and that HSP has a protective effect against these toxic effects.

Nigella sativa oil protects against emamectin benzoate-Induced neurotoxicity in rats.

This study evaluated the ameliorative impact of Nigella sativa oil (NSO) on emamectin benzoate (EMB) neurotoxicity. Thirty-five male rats were randomly allocated into 5 groups (n = 7). G1 (control): received distilled water; G2: received NSO (3 ml. Kg-1 B.W.) for 6 weeks; G3: received EMB (9 mg kg-1 B.W.) for 6 weeks; G4: was co-treated with NSO and EMB for 6 weeks; G5: was treated with EMB for 4 weeks then, received NSO for 2 weeks. All treatments were given orally every other day. EMB increased serum urea, creatinine levels; brain dopamine, serotonin, malondialdehyde levels; brain expression levels of caspase 3 and TNF-α. While, it decreased serum total protein, albumin, brain GABA, AChE, GSH-Px, CAT, and SOD levels. Histopathological findings revealed hemorrhage, congestion, severe degeneration, and edema of the brain tissues. NSO reversed the EMB-induced biochemical and histopathological alterations. This NSO effect is mostly due to its antioxidant, antiinflammatory, and antiapoptotic activities. These findings suggest NSO as a potential protective and therapeutic agent for EMB-induced neurotoxicity.

Investigation of cytotoxicity and genotoxicity of abamectin pesticide in Allium cepa L.

The present study was conducted to investigate the cytotoxicity and genotoxicity induced by abamectin pesticide in Allium cepa L. bulbs. Following 72-h exposure to different doses (0.025 ml/L, 0.050 ml/L, and 0.100 ml/L) of abamectin, growth level, micronuclei abundance, mitotic index, chromosomal aberrations, malondialdehyde content, meristematic cell damages, and total activities of superoxide dismutase and catalase were explored. The results revealed that all concentrations of abamectin were capable of inducing significant and dose-dependent changes in all parameters. Increasing doses of abamectin caused remarkable decreases in germination ratio, weight gain, and root elongation. Due to abamectin-induced genotoxicity, the mitotic index declined, while chromosomal abnormalities listed as micronucleus, fragment, sticky chromosome, unequal distribution of chromatin, bridge, vacuole nucleus, nucleus damage, and multipolar anaphase. Depending on the oxidative stress caused by abamectin administration, the total activities of superoxide dismutase and catalase enzymes increased significantly along with the malondialdehyde content. Indistinct transmission tissue, epidermis cell deformation and flattened cell nucleus were the meristematic cell damages in pesticide-applied groups. Findings of the present study revealed that abamectin is a risky pesticide with a variety of cytotoxic and genotoxic effects in non-targeted organisms. A. cepa is a promising material for biomonitoring the toxicity of abamectin.

Hydrogen peroxide treatment and its impacts on Lepeophtheirus salmonis originating from the Bay of Fundy, Canada.

Hydrogen peroxide (H2 O2 ) is used to treat sea lice infections of farmed salmonids in the Atlantic and Pacific Oceans and issues with resistance to this treatment, and others are a major threat to the sustainability of the industry. The objectives of this study were to determine how H2 O2 exposure affects survival and antioxidant-related gene expression in salmon lice (Lepeophtheirus salmonis) collected from the Bay of Fundy, New Brunswick. The maximum recommended dose of H2 O2 is 1,800 mg/L, while the EC50 values (with 95% CI) for the population tested were 1,486 (457, 2,515) mg/L for males and 2,126 (984, 3,268) mg/L for females. Neither temperature nor pretreatment with emamectin benzoate (EMB) impacted survival after H2 O2 exposure. RT-qPCR was performed on pre-adult sea lice exposed to H2 O2 and showed that four genes classically involved in the response to oxidative stress were unchanged between treated and control groups. Seven genes were found to be significantly upregulated in males and one in females. This is the first report on the efficacy and molecular responses of Atlantic Canada sea lice to H2 O2 treatment.

Effect of processing on the reduction of pesticide residues in a traditional Chinese medicine (TCM).

The behaviour of residues of tebuconazole, prochloraz, and abamectin in rehmannia during rehmannia decoction processing was systemically assessed. The pesticides were determined by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) after each processing step including washing, steaming and drying, carbonising, and boiling. Results showed that the pesticide residues significantly decreased after the steps of washing, carbonising, and boiling. Washing reduced pesticide residues by 41.2%-60.0%; carbonising reduced pesticides by 27.1%-71.1% in both prepared rehmannia and unprepared rehmannia. After boiling, the concentrations of tebuconazole and prochloraz were 0.0002-0.0022 mg kg-1 in decoctions. Abamectin was not detected in rehmannia after carbonising, and it was not detected in decoctions either. The processing factors (PFs) were less than 1 during food processing, indicating that the full set of processing can reduce the residues of tebuconazole, prochloraz, and abamectin in rehmannia decoction.

Vitamin E and selenium administration synergistically mitigates ivermectin and doramectin-induced testicular dysfunction in male Wistar albino rats.

Avermectins are broad-spectrum antiparasitic drugs in veterinary and human medication. The current study aimed to examine the toxic effects of ivermectin (IVM) and doramectin (DRM), with or without co-treatment of vitamin E (Vit.E) and selenium (Se) on apoptosis, oxidative stress and male fertility in Wistar rats. Twenty five adult male animals were divided into five groups; G1; was control (CTL) received saline, G2; IVM (0.2 mg/kg b.w), G3; IVM plus Vit.E/Se (80/1.6 mg/kg b.w, respectively), G4; DRM (0.2 mg/kg b.w), and G5; DRM plus Vit.E/Se. Both IVM and DRM were given by subcutaneous (s.c) injections while Vit.E/Se was orally given. All treatments were administered once weekly for four consecutive weeks. By 24 h after the last treatment, the animals were sacrificed. Blood and tissue samples were collected for hematology, serobiochemistry, histopathology, and molecular assays for hepatic/ renal toxicities, oxidative stress, cell viability and fertility parameters. Apoptosis of the hepatic cells obtained from the treated rats was assayed by detection of annexin-V using the flow cytometric assay (FCA). The proliferating cellular nuclear antigen (PCNA) and DNA fragmentation in the treated rats' testicular tissues were also assayed. Moreover, the direct effects of IVM or DRM with or without concomitant administration of Vit.E/Se on testicular cells isolated from adult rat were also performed in vitro. Apoptosis of those cultured testicular cells in response to the different treatments was assayed by detection of the inhibition-concentration fifty (IC50) using the SRB method, and evaluating the viable versus apoptotic cells microscopically after staining with acridine orange-ethidium bromide (AO/EB). In conclusion, both avermectins induced apoptosis in the living and cultured cells, while those antioxidants; Vit.E and Se, reduced the oxidative stress and cytotoxicity both in vivo and in vitro, either. Furthermore, the reprotoxicity and reduced male fertility were seriously evoked by IVM, but not DRM with dramatic ameliorative effect of Vit.E/Se if concomitantly administered. Avermectins, especially ivermectin, should be given according to the dose recommended by the manufacturer company and repeated dosages should be given with Vit.E/Se.

The effects of abamectin on oxidative stress and gene expression in rat liver and brain tissues: Modulation by sesame oil and ascorbic acid.

The present work was designed to assess the modulatory effects of sesame oil (SO) and ascorbic acid (AA) on abamectin (ABM)-induced oxidative stress and altered gene expression of hepatic cytochrome P450 2E1 (CYP-2E1), p38 MAPK, and caspase-3 and cerebral P-glycoprotein (Abcb1a receptor). Male rats were distributed into five groups (6 rats/group), receiving distilled water, ABM 2 mg/kg bwt 1/5 LD50 orally for 5 days, ABM + AA 100 mg/kg bwt orally, ABM + SO 5 ml/kg bwt orally, or ABM + SO + AA at the aforementioned doses. Nineteen compounds were identified in the SO sample by GC-MS analysis, including tetradecane,2,6,10-trimethyl, octadecane, 1-hexadecanol,2-methyl, and octadecane,6-methyl. Abamectin significantly upregulated the hepatic CYP-2E1 expression with excess generation of oxidative radicals, as evident by the significant depletion of reduced glutathione and elevation of malondialdehyde concentration (p ≤ 0.05) in rat liver and brain tissues. Further, ABM significantly increased TNF-α concentration, the expression of caspase-3 and p38 MAPK in the liver, as well as p-glycoprotein and GABA-A receptor in the brain. These results were in line with the observed histopathological changes. Sesame oil and/or AA supplementation alleviated ABM-induced cell damage by modulating all tested parameters. In conclusion, ABM induces oxidative stress and increases the expression of CYP-2E1, caspase-3, and p38 MAPK in the liver, as well as P-gp and GABA-A receptor in the brain. These effects could be ameliorated by SO and AA, alone and in combination, probably due to their anti-oxidant, anti-apoptotic, and gene-regulating activities.

Repeated evolution of cytochrome P450-mediated spiroketal steroid biosynthesis in plants.

Diosgenin is a spiroketal steroidal natural product extracted from plants and used as the single most important precursor for the world steroid hormone industry. The sporadic occurrences of diosgenin in distantly related plants imply possible independent biosynthetic origins. The characteristic 5,6-spiroketal moiety in diosgenin is reminiscent of the spiroketal moiety present in anthelmintic avermectins isolated from actinomycete bacteria. How plants gained the ability to biosynthesize spiroketal natural products is unknown. Here, we report the diosgenin-biosynthetic pathways in himalayan paris (Paris polyphylla), a monocot medicinal plant with hemostatic and antibacterial properties, and fenugreek (Trigonella foenum-graecum), an eudicot culinary herb plant commonly used as a galactagogue. Both plants have independently recruited pairs of cytochromes P450 that catalyze oxidative 5,6-spiroketalization of cholesterol to produce diosgenin, with evolutionary progenitors traced to conserved phytohormone metabolism. This study paves the way for engineering the production of diosgenin and derived analogs in heterologous hosts.

Molecular cloning, characterization and functional analysis of GluCl from the oriental armyworm, Mythimna separata Walker.

Glutamate-gated chloride channels (GluCls) mediate inhibitory synaptic transmission in invertebrate nervous systems, and only one GluCl gene has been found in insects. Therefore, insect GluCls are one of the major targets of insecticides including avermectins. In the present study, a 1347 bp full-length cDNA encoding a 449-amino acid protein (named MsGluCl, GenBank ID: MK336885) was cloned from the oriental armyworm, Mythimna separata, and characterized two alternative splicing variants of MsGluCl. The protein shares 76.9-98.6% identity with other insect GluCl isoforms. Spatial and temporal expression analysis revealed that MsGluCl was highly expressed in the 3rd instar and adult head. Dietary ingestion of dsMsGluCl significantly reduced the mRNA level of MsGluCl and decreased abamectin mortality. Thus, our results reveal that MsGluCl could be the molecular target of abamectin and provide the basis for further understanding the resistance mechanism to abamectin in arthropods.

Cu/ZnSOD always responded stronger and rapider than MnSOD in Lymantria dispar larvae under the avermectin stress.

Metalloenzyme SODs play important roles in insects dealing with environmental stress. Here, we cloned the Cu/ZnSOD (LdCZS) and MnSOD (LdMS) mRNA of Lymantria dispar by rapid amplification of cDNA ends (RACE). Afterwards their expression patterns were detected by quantitative real-time polymerase chain reaction (qPCR) after bioinformatic analysis. We found that both LdCZS and LdMS were widely detected in all gypsy moth larvae and all five tissues that we analyzed, and both of them were up-regulated after larvae were fed with avermectin of sublethal concentration and LC10. The LdCZS expression value are always higher than LdMS after treating with avermectin of sublethal concentrations. In addition, temporal expression profile in avermectin treated larvae showed that LdCZS expressed highest at 2nd hour, and LdMS expressed highest at 6th hour. The cuticulas transcribed LdCZS and LdMS significantly higher than heads, fat bodies, Malpighian tubes, and midguts after spraying avermectin of sublethal concentration. These results suggested that both Cu/ZnSOD and MnSOD are important antioxidant enzymes in L. dispar defensing against pesticide stress, and LdCZS always responded rapider and stronger than LdMS.

The effect of α-tocopherol and dithiothreitol in ameliorating emamectin benzoate cytotoxicity in human K562 cells involving the modulation of ROS accumulation and NF-κB signaling.

Emamectin benzoate (EMB) toxicity contributes a potential risk to environment and human health. To investigate the effect of α-tocopherol (VitE) and dithiothreitol (DTT) in ameliorating EMB-induced cytotoxicity in human K562 cells, in vitro cultured human K562 cells were incubated with different concentrations of EMB in supplement with VitE and DTT when the cells were in the logarithmic phase. Next, the cell growth inhibition was evaluated using the MTT assay and cellular morphology observation. Reactive oxygen species (ROS) production was monitored using DCFH-DA probe and NF-κB signaling was determined using Western blotting. The results demonstrated that treatment with EMB (time- and concentration-dependent) showed significantly greater inhibition on K562 cell viability, heavier chromatin condensation and DNA fragmentation, and stronger suppression of NF-κB/p105 and p65/RelA expression of K562 cells than the control group (p < 0.01). The supplementation of VitE or DTT could help protect K562 cells against EMB-induced cytotoxicity by improving cell viability, preventing ROS accumulation and up-regulating NF-κB signaling through their ameliorating effects against oxidative stress induced by EMB. VitE had a stronger synergistic effect in limiting EMB cytotoxicity than DTT. Our findings indicate that VitE and DTT are potent antioxidants for human K562 cells, offering a promising means of ameliorating EMB cytotoxicity.

Production responses and cost-benefit of long-acting pre-lambing anthelmintic treatment of yearling ewes in two commercial flocks in New Zealand.

AIMS: To investigate the production responses and cost-benefit of administering a controlled-release anthelmintic capsule (CRC) to pregnant yearling ewes prior to lambing. METHODS: Yearling ewes from two commercial sheep flocks (A, n=489; B, n=248) in the North Island of New Zealand were enrolled in the study. Prior to lambing, CRC containing albendazole and abamectin were administered to half the ewes while the other half remained untreated. Ewe liveweights and body condition scores were measured prior to lambing, at weaning and, for Flock B, prior to subsequent mating. Lambs were matched to dams shortly after birth and the weight and number of lamb weaned per ewe were determined. A cost-benefit analysis was undertaken for Flock B considering the increased weight of lamb weaned per ewe, and the weight of ewes at the next mating and the benefit in terms of lambs born. RESULTS: The mean weight at weaning of treated ewes was greater for treated than untreated ewes by 2.76 (95% CI 0.64-4.88) kg in Flock A (p<0.001) and 2.35 (95% CI -0.41-5.12) kg in Flock B (p=0.003); the weight of lamb weaned per ewe was greater for treated than untreated ewes by 1.43 (95% CI -0.71 to -3.49) kg in Flock A (p=0.041) and 3.97 (95% CI 1.59-6.37) kg in Flock B (p<0.001), and ewe liveweight prior to subsequent mating was greater for treated than untreated ewes in Flock B by 4.60 (95% CI 3.6-5.6) kg (p<0.001). There was no difference in the percentage of lambs reared to weaning between treated and untreated ewes in either flock (p>0.8). The overall cost-benefit of treatment for Flock B was NZ$9.44 per treated ewe. CONCLUSIONS AND CLINICAL RELEVANCE: Pre-lambing CRC administration to yearling ewes resulted in increased ewe weaning weights and weight of lamb weaned in both the flocks studied. There was an economic benefit in the one flock where this was assessed.

Economic viability of anthelmintic treatment in naturally infected beef cattle under different nutritional strategies after weaning.

The aim of the present study was to evaluate the effects of treatment with different anthelmintic compounds on the productivity of naturally infected calves and the economic viability of these treatments within extensive breeding systems employing different nutritional strategies after weaning. For this purpose, 4 farms with 42-60 calves naturally infected with gastrointestinal nematodes were selected. The calves were distributed into 6 groups (7-10 animals each) per farm and treated with ivermectin 1%, ivermectin 3.15%, eprinomectin 5%, levamisole 7.5%, albendazole 15%, and control group (no treatment). These animals were evaluated over an experimental period of 150 days. Levamisole 7.5% presented the best capacity for the reduction of eggs per gram (EPG) of feces in all herds evaluated, followed by albendazole 15% and eprinomectin 5%. Parasite resistance to multiple drugs was found in all herds, especially those of Cooperia, Haemonchus, Oesophagostomum, and Trichostrongylus. For farm 1, differences in weight gain and EPG reduction percentages led to a difference of US$285.06 between the levamisole and ivermectin 3.15% groups. Similar findings were noted for the levamisole and ivermectin 1% groups of farm 3, with a difference of US$399.37 because of the final weight gain in these groups. For farms 2 and 4, the ivermectin 3.15% and control groups, respectively, were the most profitable; these unexpected results were possibly influenced by variables not measured during the experimental period. This study suggested that anthelmintic treatments should always precede an efficacy test, once they are demonstrated to be most profitable under adequate breeding conditions, to ensure adequate control of gastrointestinal nematode infection.

The effects of emamectin benzoate or ivermectin spiked sediment on juvenile American lobsters (Homarus americanus).

This study examined the effects of a range of ½-log concentrations of emamectin benzoate (commercially applied as SLICE®) and ivermectin (commercially applied as IVOMEC®) on juvenile American lobster, Homarus americanus. Phase I of the research assessed acute (up to 4 days) and chronic (30-day) toxicity of sediment dosed with the active ingredients emamectin benzoate (EMB) formulated as SLICE® or ivermectin (IVM) formulated as IVOMEC® at various nominal concentrations (EMB: 15, 48, 150, 475 and 1500 ng g-1 wet sediment; IVM: 3, 9.5, 30, 95 and 300 ng g-1 wet sediment) on juvenile Atlantic lobster (stages IV). Phase II evaluated sublethal effects (e.g., growth, moulting success) of all lobster surviving past the 30 day exposure period, over an additional 41 days. Chemical analysis of EMB and IVM in sediment samples from the exposure tanks revealed a strong linear association (R2 values 0.99 and 0.98 for EMB and IVM, respectively) between nominal dose and measured concentration of compound. EMB exposure concentrations at very high levels (≥ 343.3 ng g-1) were acutely toxic to juvenile lobster such that 100% of lobsters had died after 13 days of exposure. The maximum cumulative mortality of lobsters exposed to the highest concentrations of EMB and IVM was 100% after 10 days and 25 days, respectively. The 10-day LC50 estimates (±â€¯95% CI) for EMB and IVM were 250.23 ±â€¯90.4 and 212.14 ±â€¯202.64 ng g-1, respectively. Using abnormal behaviour as an indicator, the 15-day EC50 estimates (±â€¯95% CI) for EMB and IVM were 96.19 ±â€¯51.42 and 15.82 ±â€¯6.93 ng g-1, respectively. The NOEC (no observed effect concentration) for abnormal behaviour was 0.0 ng g-1 for each product and the LOEC (lowest observed effect concentration) was 8.8 and > 3.0 ng g-1 for EMB and IVM, respectively. Observations on sublethal effects included delayed moulting to stage VI and reduced growth at higher exposure concentrations for both therapeutants. Using failure to moult to stage V or VI as an indicator, the 15-day EC50 estimates (±â€¯95% CI) for EMB and IVM were 32.72 ±â€¯18.26 and 14.00 ±â€¯12.43 ng g-1, respectively. The NOEC for failure to moult to stage V only was 343.3 and 14.7 ng g-1 for EMB and IVM, respectively. Whereas, the LOEC was 1066.7 and > 61.0 ng g-1 for EMB and IVM, respectively. The concentrations of EMB and IVM tested in the present study were acutely toxic to juvenile lobster exposed to the highest dosages (343.3 and 1066.7 ng EMB g-1 and 61.0 and 300.0 ng IVM g-1). There was significant evidence of chronic toxicity, longer exposure increased mortality with LT50 values decreasing with increasing test material concentration.

Industrial prune processing and its effect on pesticide residue concentrations.

The aim of this study was to determine the insecticide residue processing factor (PF) from plums to prunes and the effect of the industrial processing of prunes residue concentrations. Our results show an increase of insecticide concentrations during plum dehydration that is explained by fruit water loss; however, the normalized insecticide residue concentration, based on plum dry weights to compensate dehydration, was reduced. The water washing and tenderizing of prunes produced insecticide residue reductions of 22.9 ±â€¯4.5% and 21.9 ±â€¯4.2%, respectively. PF were: 1.157, 1.872, 1.316, 0.192, 2.198, 0.775 and 0.156 for buprofezin, l-cyhalothrin, spirodiclofen, indoxacarb, acetamiprid, imidacloprid and emamectin benzoate, respectively, being directly related to water solubility, aqueous hydrolysis and degradation point and inversely related to molecular mass and melting point. In plums for the dehydrated agroindustry the final product is prunes, therefore, it is crucial to consider the PF to determine the specific preharvest interval for this important agroindustry.

Lethal and Sublethal Effects on Tamarixia triozae (Hymenoptera: Eulophidae), an Ectoparasitoid of Bactericera cockerelli (Hemiptera: Triozidae), of Three Insecticides Used on Solanaceous Crops.

Lethal and sublethal effects of refined soybean oil, imidacloprid, and abamectin on Tamarixia triozae (Burks; Hymenoptera: Eulophidae) were assessed after exposure of the eggs, larvae, and pupae of this parasitoid to three concentrations of these active substances: the LC50 for fourth-instar Bactericera cockerelli (Sulc.; Hemiptera: Triozidae) and 50% and 100% of the minimum field-registered concentration (MiFRC). Soybean oil caused 26-61% mortality in T. triozae eggs and 6-19% in larvae; mortality in both eggs and larvae was ≤19% for imidacloprid and 4-100% for abamectin. All three compounds caused <18% mortality of T. triozae pupae, with the exception of the abamectin 50% (47%) and 100% (72%) MiFRC. The mortality of larvae and pupae derived from treated eggs was ≤39% for all three insecticides, and that of pupae derived from treated larvae was ≤10%. In general, emergence of adults developed from treated eggs, larvae, and pupae was affected more by abamectin than by the other treatments. The proportion of females derived from all three development stages was not affected by treatment with the compounds, except when the parasitoid was treated as larvae with the soybean oil 100 and 50% MiFRC (66 and 68%, respectively) or when treated as pupae with the imidacloprid LC50 and 100% MiFRC (~60%). Female longevity was generally higher than that of males. The use of imidacloprid, soybean oil, and abamectin in combination with T. triozae for pest control may be effective when the parasitoid is in the pupal stage because this stage is less susceptible than other immature stages.

Attenuating effects of caffeic acid phenethyl ester and betaine on abamectin-induced hepatotoxicity and nephrotoxicity.

Abamectin (ABM) is a widely utilized potent anthelmintic and insecticidal agent. In this study, we investigated the protective effects of caffeic acid phenethyl ester (CAPE) and betaine (BET) against ABM-induced hepatotoxicity and nephrotoxicity in rats. Forty rats were divided into five groups, receiving either oral saline solution (normal control), oral ABM at a dose of 2 mg/kg BW (1/5 LD50), CAPE (10 µmol/kg BW intraperitoneally) followed by ABM, or BET supplementation at a dose of 250 mg/kg BW followed by ABM administration, while group V rats received a combination of i.p. CAPE and oral BET in the same doses before receiving ABM. Biochemical analysis showed that ABM administration significantly (p < 0.05) increased serum levels of aminotransferases, alkaline phosphatase, lactate dehydrogenase, and cholesterol, as well as serum creatinine and urea. Compared to the control group, ABM-intoxicated rats had significantly (p < 0.05) higher tissue concentrations of nitric oxide and malondialdehyde, as well as lower tissue glutathione concentration, total antioxidant capacity, and antioxidant enzymatic activity (glutathione peroxidase, superoxide dismutase, and catalase). Histopathological examination of hepatic and renal tissues of ABM-intoxicated rats showed acute inflammatory and necrotic changes. Pretreatment with CAPE and/or BET reversed the biochemical and histopathological alterations of ABM on the liver and kidneys. Therefore, CAPE and BET (alone or in combination) could be promising protective agents against ABM-induced hepatotoxicity and nephrotoxicity. Future studies should confirm our findings and evaluate the other molecular effects are involved in the combination chemoprotection of CAPE and BET.

Preclinical evaluation of avermectins as novel therapeutic agents for alcohol use disorders.

The deleterious effects of alcohol use disorders (AUDs) on human health have been documented worldwide. The enormous socioeconomic burden coupled with lack of efficacious pharmacotherapies underlies the need for improved treatment strategies. At present, there is a growing body of preclinical evidence that demonstrates the potential of avermectins [ivermectin (IVM), selamectin (SEL), abamectin (ABM), and moxidectin (MOX)] in treatment of AUDs. Avermectins are derived by fermentation of soil micro-organism, Streptomyces avermitilis, and have been extensively used for treatment of parasitic infections. From the mechanistic standpoint, avermectins are positive modulators of purinergic P2X4 receptors (P2X4Rs). P2X4Rs belong to P2X superfamily of cation-permeable ion channels gated by adenosine 5'-triphosphate (ATP). Building evidence has implicated a role for P2X4Rs in regulation of ethanol intake and that ethanol can inhibit ATP-gated currents in P2X4Rs. Investigations using recombinant cell models and animal models of alcohol drinking have reported that IVM, ABM, and MOX, but not SEL, were able to antagonize the inhibitory effects of ethanol on P2X4Rs in vitro and reduce ethanol intake in vivo. Furthermore, IVM was shown to reduce ethanol consumption via P2X4R potentiation in vivo, supporting the involvement of P2X4Rs in IVM's anti-alcohol effects and that P2X4Rs can be used as a platform for developing novel anti-alcohol compounds. Taken together, these findings support the utility of avermectins as a novel class of drug candidates for treatment of AUDs.