Study of the cardioprotective effects of crocin on Human Cardiac Myocyte cells and reduction of oxidative stress produced by aluminum phosphide poisoning.

OBJECTIVES: The effects of Crocin as a cardioprotective material against Aluminum phosphide poisoning by reducing the oxidative stress is investigated. METHODS: The level of biomarkers of oxidative stress (Catalase, Superoxide dismutase, Malondialdehyde and Protein carbonyl) were measured in the cell culture model on Human Cardiac Myocyte cells to detect the protective effect of crocin. Initially, to define the pure impact of aluminum phosphide poison and crocin on the heart cells, their effects on the biomarkers quantity in cell line were measured, separately, using the standard related kits. Later the effect of crocin with different concentration as a treatment on the oxidative stress biomarkers of the poisoned heart cells were monitored. Note that in pre-treatment case, the crocin was initially added to the cells before poisoning them. Data were analyzed using the analysis of variance method. KEY FINDINGS: Results showed that crocin treatment reduced the aluminum phosphide (AlP) poisoning effect significantly. The treatment resulted in substantial deviation in the biomarkers of oxidative stress at the pre- and post-treatment phases for all groups. The oxidative markers values of the poisoned cells were recovered by crocin treatment. CONCLUSIONS: Crocin is proposed as a potentially powerful antioxidant to treat the cardiotoxicity caused by aluminum phosphide poisoning.

Physiological and biochemical responses of Microcystis aeruginosa to phosphine.

The frequent outbreaks of cyanobacteria bloom are often accompanied by the generation and release of reduced phosphorus species (e.g., phosphine), which raises interesting questions regarding their potential algae-related effects. To clarify the physiological and biochemical responses of cyanobacteria to phosphine, Microcystis aeruginosa was treated with different concentrations of phosphine. Net photosynthetic rate, total antioxidant capacity (T-AOC), catalase (CAT) activity, and the concentrations of chlorophyll a, carotenoid and total protein were investigated and scanning electron microscopy (SEM) was conducted to elucidate the physiological and biochemical responses of M. aeruginosa to phosphine. The results showed that phosphine was beneficial to the growth of algal cells after M. aeruginosa acclimatized to the treatment of phosphine, and treatment with 2.48 × 10-2 mg/L phosphine had a greater positive effect on the growth and reproduction of M. aeruginosa than 7.51 × 10-3 mg/L phosphine, in which most algal cells were smooth and flat on day 16. Treatment with the high concentration of phosphine (7.51 × 10-2 mg/L) for 16 d reduced T-AOC, CAT activity, net photosynthetic rate, and the concentrations of chlorophyll a, carotenoid and total protein of M. aeruginosa to the minimums, resulting in the lysis and death of M. aeruginosa cells, which indicates phosphine has a toxic effect on the growth of algal cells. However, the high concentration of phosphine (7.51 × 10-2 mg/L) had a greater positive effect on the growth of M. aeruginosa cells than the lower two (7.51 × 10-3 mg/L and 2.48 × 10-2 mg/L) from 3 d to 12 d. Our findings provide insight into how phosphine potentially affects the growth of M. aeruginosa cells and the important roles of elevated phosphine on the outbreak of cyanobacteria bloom.

Neurotoxicological and thyroid evaluations of rats developmentally exposed to tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) and tris(2-chloro-2-ethyl)phosphate (TCEP).

Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) and tris(2-chloro-2-ethyl)phosphate (TCEP) are organophosphorous flame retardants with widespread usage and human exposures through food, inhalation, and dust ingestion. They have been detected in human tissues including urine and breast milk. Reports of disrupted neural growth in vitro, abnormal development in larval zebrafish, and altered thyroid hormones in several species have raised concern for neurodevelopmental toxicity. This is especially the case for TDCIPP, which is more potent and has more activity in those assays than does TCEP. We evaluated the potential for developmental neurotoxicity of TDCIPP and TCEP in a mammalian model. Pregnant Long-Evans rats were administered TDCIPP (15, 50, or 150 mg/kg/day) or TCEP (12, 40, 90 mg/kg/day) via oral gavage from gestational day 10 to weaning. Corn oil was the vehicle control in both studies. Body weight and righting reflex development were monitored in all pups. A subset of offspring at culling and weaning, and dams at weaning, were sacrificed for serum and organ collection for measurement of brain, liver, and thyroid weights, serum thyroid levels, and serum and brain acetylcholinesterase activities. Brain weights were also measured in a group of adult TDCIPP-treated offspring. One male and one female from each litter were allocated for behavioral testing at several ages: standard locomotor activity (preweaning, postweaning, adults), locomotor activity including a lighting change mid-way (postweaning, adults), elevated zero maze (postweaning, adults), functional observational battery (FOB; postweaning, adults), and Morris water maze (place learning, reference and working memory; adults). Neither chemical produced changes in maternal body weight or serum thyroid hormones, but relative liver weight was increased at the high doses of both TDCIPP and TCEP. In offspring, there were no effects on viability, litter size, or birth weight. With TDCIPP, absolute liver weights were lower at weaning and weight gain was lower in the high-dose offspring until about two months of age. Thyroid hormones and brain weights were not altered and acetylcholinesterase (both brain and serum) was not inhibited by either chemical. TDCIPP-treated offspring showed slight differences in floating in the water maze, hindlimb grip strength, and altered activity habituation, whereas TCEP-treated rats showed differences in quadrant time (probe) and middle-zone preference in the water maze. Regarding these few changes, the effects were minimal, mostly not related to dose, and did not appear treatment-related or biologically significant. Overall, these data do not support the potential for thyrotoxicity or developmental neurotoxicity produced by TDCIPP or TCEP.

TPP and TCEP induce oxidative stress and alter steroidogenesis in TM3 Leydig cells.

Effects of triphenyl phosphate (TPP) and tris-(2-chloroethyl) phosphate (TCEP) exposure on induction of oxidative stress and endocrine disruption were investigated in TM3 cells. After 24h exposure, cell growth declined and morphology changed in TPP and TCEP treated groups with high dosages. Significant increases in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S-transferase (GST) activities and their respective gene expressions in a dose-dependent and/or time-dependent manner in TPP or TCEP groups. Moreover, the expression of main genes related to testosterone (T) synthesis including cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), cytochrome P450 17α-hydroxysteroid dehydrogenase (P450-17α), 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD) were dramatically reduced by TPP and TCEP treatments, especially with the high dosage for 24h. TPP and TCEP treatments for 24h caused significant decreases in T levels in the medium. Furthermore, co-treatments of hCG with TPP or TCEP could inhibit hCG-induced changes in the expression of P450scc, P450-17α and 17ß-HSD and T levels. Taken together, TPP and TCEP could induce oxidative stress and endocrine disruption in TM3 cells.

In vivo toxicity assessment of non-cadmium quantum dots in BALB/c mice.

Along with widespread usage of QDs in electronic and biomedical industries, the likelihood of QDs exposure to the environment and humans is deemed to occur when the QD products are degraded or handled as waste for processing. To date, there are very few toxicological reports available in the literature for non-cadmium QDs in animal models. In this work, we studied the long term in vivo toxicity of InP/ZnS QDs in BALB/c mice. The biodistribution, body weight, hematology, blood biochemistry, and organ histology were determined at a very high dosage (25 mg/kg) of InP/ZnS QDs over 84 days period. Our results manifested that the QDs formulation did not result in observable toxicity in vivo within the evaluation period, thereby suggesting that the InP/ZnS QDs can be utilized as optical probes or nanocarrier for selected in vivo biological applications when an optimized dosage is employed. FROM THE CLINICAL EDITOR: This study investigated the toxicity of quantum dots in BALB/c mice, and concluded that no organotoxicity was detectable despite of using high concentration of InP/ZnS quantum dots with prolonged exposure of 3 months.

Aluminium phosphide-induced genetic and oxidative damages in vitro: attenuation by Laurus nobilis L. leaf extract.

OBJECTIVE: The present investigation was undertaken to assess the protective effect of Laurus nobilis leaf extract (LNE) against aluminum phosphide (AIP)-induced genotoxic and oxidative damages stress in cultured human blood cells in the presence of a metabolic activator (S9 mix). MATERIALS AND METHODS: Sister chromatid exchange (SCE) and chromosome aberration (CA) assays were used to assess AlP-induced genotoxicity and to establish the protective effects of LNE. In addition, we determined total antioxidant capacity (TAC) and total oxidative status (TOS) levels in AlP and LNE treated cultures for biomonitoring the oxidative alterations. RESULTS: There was significant increases (P < 0.05) in both SCE and CA frequencies of cultures treated with AlP as compared to controls. Our results also showed that AlP (58 mg/l) caused oxidative stress by altering TAC and TOS levels. However, co-application of LNE (25, 50, 100 and 200 mg/l) and AlP resulted in decreases of SCE, CA rates and TOS level and increases of TAC level as compared to the group treated with AlP alone. CONCLUSION: The preventive role of LNE in alleviating AlP-induced DNA and oxidative damages was indicated for the first time in the present study.

Aluminum phosphide-induced genetic and oxidative damages in rats: attenuation by Laurus nobilis leaf extract.

Aluminum phosphide (AlP) is a colorless, flammable, liquefied pesticide that is commonly used to control insects, nematodes, weeds, and pathogens in crops, forests, ornamental nurseries, and wood products. Early investigations of AlP-poisoned mammalian cells led to the proposed involvement of oxidative damage in its toxicity mechanism. Therefore, this study was aimed to evaluate the effect of Laurus nobilis (L) leaf extract (LNE) against AlP-induced genetic and oxidative damages in rats. Selected animals were assigned to four groups (n = 6), namely, group A: control (only distilled water is injected); group B: AlP (4 mg kg(-1) injected intraperitoneally (i.p.)); group C: LNE (200 mg kg(-1) injected i.p.), and group D: AlP plus LNE, respectively. The experimental period lasted for 14 successive days. Chromosomal aberrations (CAs) and micronucleus (MN) assay were used for monitoring genotoxic damage. In addition, biochemical parameters such as total antioxidant capacity (TAC) and total oxidative status (TOS) were examined in serum samples to determine oxidative damage. Our results indicated that AlP caused increase in CA and MN assay rates and alterations in TAC and TOS levels when compared with control group. On the contrary, LNE did not change the rates of both the analyzed cytogenetic end points and led to increase in TAC level. Moreover, we observed that LNE suppressed the genetic damage by AlP to bone marrow cells in vivo. Interestingly AlP-induced oxidative stress was also strongly reduced by LNE. The results of the present study indicated that the protective effect of LNE might be ascribable to its antioxidant and free radical scavenging properties.

Effect of sweet almond oil on survival rate and plasma cholinesterase activity of aluminum phosphide-intoxicated rats.

INTRODUCTION: Aluminum phosphide (ALP), as an effective pesticide and a substance used for protecting rice during storage, has become one of the commonest causes of poisoning and even suicide in developing countries including Iran and India. The authors aimed to study the efficacy of sweet almond oil as an antidote in ALP toxicity. METHODS: The present experimental study was conducted over 35 rats. The animals were divided into four groups: one group as the control group and three other groups which received ALP alone or ALP and sweet almond oil with different time intervals. In addition to estimating the survival rate of the animals, plasma cholinesterase activity as a possible factor affected in ALP poisoning was evaluated. RESULTS: Treatment by intragastric irrigation of sweet almond oil resulted in significant reduction of mortality. Moreover, mean plasma cholinesterase levels were inhibited in groups receiving ALP. CONCLUSION: Oral sweet almond oil, if especially used immediately after poisoning with ALP, improves the survival rate.

Comparative toxicity of fumigants and a phosphine synergist using a novel containment chamber for the safe generation of concentrated phosphine gas.

BACKGROUND: With the phasing out of ozone-depleting substances in accordance with the United Nations Montreal Protocol, phosphine remains as the only economically viable fumigant for widespread use. However the development of high-level resistance in several pest insects threatens the future usage of phosphine; yet research into phosphine resistance mechanisms has been limited due to the potential for human poisoning in enclosed laboratory environments. PRINCIPAL FINDINGS: Here we describe a custom-designed chamber for safely containing phosphine gas generated from aluminium phosphide tablets. In an improvement on previous generation systems, this chamber can be completely sealed to control the escape of phosphine. The device has been utilised in a screening program with C. elegans that has identified a phosphine synergist, and quantified the efficacy of a new fumigant against that of phosphine. The phosphine-induced mortality at 20 degrees C has been determined with an LC(50) of 732 ppm. This result was contrasted with the efficacy of a potential new botanical pesticide dimethyl disulphide, which for a 24 hour exposure at 20 degrees C is 600 times more potent than phosphine (LC(50) 1.24 ppm). We also found that co-administration of the glutathione depletor diethyl maleate (DEM) with a sublethal dose of phosphine (70 ppm,

Systemic vascular disease in male B6C3F1 mice exposed to particulate matter by inhalation: studies conducted by the National Toxicology Program.

Epidemiological studies suggest an association between ambient particulate matter and cardiopulmonary diseases in humans. The mechanisms underlying these health effects are poorly understood. To better understand the potential relationship between particulate-matter-induced inflammation and vascular disease, a 2-phase retrospective study was conducted. Phase one included the review of heart, lung, and kidney tissues from high-dose and control male B6C3F1 mice exposed by inhalation to 9 particulate compounds for a 2-year period. The results showed that high-dose males developed significantly increased incidences of coronary and renal arteritis over controls in 2 of the 9 studies (indium phosphide and cobalt sulfate heptahydrate), while marginal increases in arteritis incidence was detected in 2 additional studies (vanadium pentoxide and gallium arsenide). In contrast, arteritis of the muscular arteries of the lung was not observed. Morphological features of arteritis in these studies included an influx of mixed inflammatory cells including neutrophils, lymphocytes, and macrophages. Partial and complete effacement of the normal vascular wall architecture, often with extension of the inflammatory process into the periarterial connective tissue, was observed. Phase 2 evaluated the heart, lung, kidney, and mesentery of male and female B6C3F1 mice from the 90-day studies of the 4 compounds demonstrating arteritis after a 2-year period. The results showed arteritis did not develop in the 90-day studies, suggesting that long-term chronic exposure to lower-dose metallic particulate matter may be necessary to induce or exacerbate arteritis.

The role of oxidative stress in indium phosphide-induced lung carcinogenesis in rats.

Indium phosphide (IP), widely used in the microelectronics industry, was tested for potential carcinogenicity. Sixty male and 60 female Fischer 344 rats were exposed by aerosol for 6 h/day, 5 days/week, for 21 weeks (0.1 or 0.3 mg/m(3); stop exposure groups) or 105 weeks (0 or 0.03 mg/m(3) groups) with interim groups (10 animals/group/sex) evaluated at 3 months. After 3-month exposure, severe pulmonary inflammation with numerous infiltrating macrophages and alveolar proteinosis appeared. After 2 years, dose-dependent high incidences of alveolar/bronchiolar adenomas and carcinomas occurred in both sexes; four cases of squamous cell carcinomas appeared in males (0.3 mg/m(3)), and a variety of non-neoplastic lung lesions, including simple and atypical hyperplasia, chronic active inflammation, and squamous cyst, occurred in both sexes. To investigate whether inflammation-related oxidative stress functioned in the pathogenesis of IP-related pulmonary lesions, we stained lungs of control and high-dose animals immunohistochemically for four markers indicative of oxidative stress: inducible nitric oxide synthase (i-NOS), cyclooxygenase-2 (COX-2), glutathione-S-transferase Pi (GST-Pi), and 8-hydroxydeoxyguanosine (8-OHdG). Paraffin-embedded samples from the 3-month and 2-year control and treated females were used. i-NOS and COX-2 were highly expressed in inflammatory foci after 3 months; at 2 years, all four markers were expressed in non-neoplastic and neoplastic lesions. Most i-NOS staining, mainly in macrophages, occurred in chronic inflammatory and atypical hyperplastic lesions. GST-Pi and 8-OHdG expression occurred in cells of carcinoma epithelium, atypical hyperplasia, and squamous cysts. These findings suggest that IP inhalation causes pulmonary inflammation associated with oxidative stress, resulting in progression to atypical hyperplasia and neoplasia.

[ Dynamics of NAD-dependent isocitrate dehydrogenase activity in homogenized rat liver exposed to toxic products of the phosphorus industry]. / Dinamika akivnosti NAD-zavisimoi izotsitratdegidrogenazy v gomogenatakh pecheni krys pod deistviem vrednykh veshchestv fosfornogo proizvodstva.

Dynamic studies showed that the combined action of phosphine and hydrofluoric acid damages the Krebs cycle reactions, dehydrogenization of isocitrate and synthesis of citrate in homogenized rat liver. Yellow phosphorus harmed the citrate synthetic reaction of citric acid cycle in homogenized rat liver as well. That activated the alternative action principles in the cycle. The main cause of such disorders in the Krebs cycle in likely to be the abnormal fat metabolism induced by toxic products of phosphorus industry.

Synthfsis of bis(aziridinyl)phosphinyl-N-hydroxyurethane derivatives as antineoplastic agents.

Several new "dual antagonists" were synthesized in which the 2,2-dimethyl (or ring C unsubstituted) aziridine phosphinyl function is linked to N-hydroxyurethane rather than the urethane moiety. Three of the new compounds showed very high activities against leukemia L1210 in mice.