An Evaluation of the Plasma Levels of Frequently Used Pesticides in Dairy Cattle and Its Possible Correlation with the Occurrence of Follicular Cystic Ovarian Disease: A Case-Control Study

Background: Cystic ovarian disease (COD) is one of the common reproductive disorders which affecting the fertility of dairy cattle induces heavy financial burdens on herds owners. Various insecticides, fungicides and herbicides, collectively known as pesticides are frequently used in the agricultural systems of different countries. Given the fact that pesticides are known to have endocrine disrupting properties, exposure to these compounds may play a role in the development of COD.Materials and Methods: The plasma concentrations of a complete profile of common pesticides including organophosphorus, organochlorine, and carbamate and pyrethroid compounds in the plasma of cattle with COD compared to healthy controls was examined. Moreover, plasma concentrations of inflammatory cytokines as well as oxidative stress parameters were investigated.Results: No significant amounts of any of the pesticides investigated were detectable in the plasma of neither the healthy nor cystic cows. The plasma indices of total antioxidant capacity (TAC), thiol, lipid peroxidation (LPO), and reactive oxygen species (ROS) did not show any significant differences between the affected and the control groups. Tumor necrosis factors alpha (TNF-α), progesterone, lymphocyte, neutrophil, fibrinogen and MCHC had significantly higher amounts in the plasma of COD cows.Conclusion: Findings of the present study do not support the notion that exposure to the studied pesticides is a contributing factor in the development of follicular cysts in dairy cattle. In addition, TNF-α might be affected as a factor in the pathogenesis of COD by an independent pathway of pesticides effect

Estrogenic Activity of Some Phytoestrogens on Bovine Oxytocin and Thymidine Kinase-ERE Promoter through Estrogen Receptor-α in MDA-MB 231 Cells

Background: Phytoestrogens, a group of plant-derived polyphenolic compounds have recently come into considerable attention due to the increasing information on their potential adverse effects in human health. Some of phytoestrogens show estrogenic activity that may be carcinogenic for human. In the present study, we investigated the transcriptional effects of variety of phytoestrogens on the bovine oxytocin and the thymidine kinase-ERE promoter by estrogen receptor α in MDA-MB 231 breast cancer cell line. Materials and Methods: Cells were seeded for transfections into 12- well plates at a density of 100000 cells per well were transfected with a total of 3 μg of plasmid DNA using calcium phosphate coprecipitation. Estrogen and some phytoestrogens (naringenin, 8-prenyl-naringenin and 6-( 1, 1 - dimethylallyl ) naringenin were used for the stimulation of transfected cells. Results: Findings of our study clearly demonstrated the subtype-selective activation of estrogen receptor (ER)α and (ER)β by the p hytoestrogen naringenin (activating estrogen receptor β) and its substituted forms 8-prenyl-naringenin and 6-( 1, 1 - dimethylallyl ) naringenin (activating estrogen receptor α) , on the ERE-controlled promoter as well as on the oxytocin gene promoter. Conclusion: The study revealed that some p hytoestrogen s show estrogenic activity by classical or non-classical mechanisms as well as exhibit estrogenic activity by undetermined mechanisms in transfected MDA-MB 231 cell line

Transcriptional effects of Organochlorine o,p′-DDT and its Metabolite p,p′-DDE in Transfected MDA-MB 231 and MCF-7 Breast Cancer Cell Lines

Background: The organochlorine DDT has estrogenic activity but the mechanism underlying the estrogenic activity of this pesticide remains unclear. In the present investigation here, we studied the transcriptional effects of a synthetic organochlorine pesticide o,p’-DDT [1.1.1.-trichloro-2-(o-chlorophenyl)-2-p-chloriphenyl ethane] and its metabolite p,p'-DDE (2-2-bis(4/chlorophenyl)-1-1-dichloroethyl) on the bovine oxytocin and the thymidine kinase-ERE promoter by estrogen receptor &alpha in MDA-MB 231 and MCF-7 breast cancer cell line. Materials and Methods: Cells were seeded for transfections into 12- well plates at a density of 100000 cells per well and were transfected with a total of 3 &mug of plasmid DNA using calcium phosphate coprecipitation. o,p’-DDT and p,p'-DDE were used for stimulation of transfected MDA-MB 231 and MCF-7 breast cancer cell lines. Results: The results showed o,p’-DDT has no agonistic activity in MDA-MB 231 cells transfected with the oxytocin promoter construct (OTwt) or the thymidine kinase-ERE promoter construct (TK ERE) and estrogen receptor &alpha. While, The results obviously show that o,p’-DDT has an agonistic effect on both the oxytocin and the thymidine kinase-ERE promoter in MCF-7 leading to a more than two-fold stimulation of transcription at 10-5 M. In addition, there is no agonistic effect with p,p'-DDE on transfected MCF-7 cells and MDA-MB 231 cell line. Conclusion: In conclusion, our results revealed that o,p’-DDT has not estrogenic activity in a classical mechanism in transfected MDA-MB 231 breast cancer cells while has estrogenic activity in a classical mechanism in transfected MCF-7 human breast cancer cell line

Evaluation of Cardiopulmonary Toxicity Following Oral Administration of Multi-walled Carbon Nanotubes in Wistar Rats

Objective(s): Carbon nanotubes have unique mechanical, electrical, and thermal properties, with potential different applications in nanomedicine, electronics, and other industries. These new applications of carbon nanotubes in different industries lead to the increased exposure risk of nanomaterials to human. Up to now, all aspects of carbon nanotubes toxicity are not completely clear following human and animal exposures with these novel compounds. The aim of this study was to assess cardiopulmonary toxicity of multi-walled carbon nanotubes following oral administration in rats with respect to the histopathological and biochemical evaluation. Methods: In the present investigation, we studied cardiorespiratory toxicity of multi-wall carbon nanotubes (MWCNT) with regard to histopathological changes and some biomarkers including TnT, CK-MB and LDH in experimental rats following oral administration. One dose per 24 h of MWCNT suspension was administered orally (gavage technique) to animals at the doses of 500, 1000 and 2000 mg/kg/day BW for 5 days. Results: The results of these study showed oral administration of MWCNT induces histopathological complications such as severe alveolar edema and hemorrhage in lungs and myocytolysis in heart of all experimental groups of animals. In all of the groups, troponin T level showed no changes when compared to baseline. Lactate dehydrogenase and CK-MB activity showed significant increment in all of animal groups following oral administration of carbon nanotubes. Conclusions: It can be concluded that oral exposure of MWCNT may be toxic for cardiovascular and respiratory systems, because MWCNT induced biochemical alterations and histopathological abnormalities in these vital systems

COVID-19: therapeutic disinformation and intoxications

The new coronavirus pandemic alarmed the world. Misinformation regarding prevention and treatment for safeguarding against this pandemic seemed to be life-threatening along with the spreading pandemic. Public health authorities in the world tried to battle this virtual virus by offering true information and correcting misinformation. However, the public misinformation through social media caused toxicological consequences in some parts of the world which provoked awareness, response, and concern of the public health authorities including the Food and Drug Administration (FDA) and the toxicology community. This study analysed the published literature on therapeutic disinformation during the COVID-19 pandemic and its toxicological effects. The electronic databases searched were Scopus, MEDLINE and Scielo. The used keywords were: “COVID-19”, “misinformation”, “social media”, “public health”, “drug toxicity”, and “education”. Finding new strategies for the prevention and treatment of the coronavirus again stresses the role of public education about true drug information. Hundreds of chemicals were/are being tested to be prophylactic medications or healing drugs for the coronavirus. Therefore, spreading accurate information and editing misinformation can be crucial. In summary, this commentary is going to bring attention to misinformation regarding prevention and treatment for safeguarding against the COVID-19 pandemic and its toxicological consequences and the need for public education on the appropriate use of therapies

Investigation of hematotoxic effect of nano ZnO, nano Fe3O4 and nano SiO2 in vitro

Objective(s): Evaluation of nanomaterials interaction with blood ingredients is a part of preclinical risk assessment of newly-synthesized materials, especially for nano-sized pharmaceuticals which are intravenously administrated. The red blood cells (RBCs) are susceptible to oxidative stress damage. This study was designed to evaluate induced oxidative hematotoxic effect of nano ZnO, Fe3O4, and nano SiO2 on human red blood cells in vitro. Methods: Blood samples were collected from healthy male volunteers. RBCs were exposed to different concentrations (50, 100, 250mg/ml) of nano ZnO, nano Fe3O4, and nano SiO2 at 4°C for 24hours. Lipid peroxidation and intracellular Glutathione (GSH) level were studied as the biomarkers of oxidative stress. Results: The results showed that the lipid peroxidation had significantly increased. However, after exposure to nanoparticles, the GSH level of RBCs considerably decreased compared to the controls (

Investigation of acute dermal irritation/corrosion, acute inhalation toxicity and cytotoxicity tests for Nanobiocide®

Objective(s): Nanomaterials, especially silver Nanoparticles (Ag-NPs), are employed in an increasing number of commercial products. This has led to an ever growing exposure of human beings to this substance. The first purpose of the Nano Committee of Food and Drug Administration of The Islamic Republic of Iran (IFDA) is developing guidelines to assess and approve commercial nano-health products for their safety of human applications. Nanobiocide® as a commercial product of stable colloid including 2000 ppm Ag-NPs for surface antimicrobial applications was investigated according to IFDA guidelines in the approval process. Methods: The first fabrication and characterization method of the product were determined. The human exposure to Nanobiocide® were studied by cytotoxicity assay, dermal irritation and inhalation toxicity assay based on the standard assay. Results: According to cytotoxicity assay by MTT method the concentration-dependent of cell viability was reduced and Inhibitory concentration-50 was about 1160 ppm. The Draize dermal irritation scoring system (DDIS) showed no irritation to the skin of rabbits. No sign of gross toxicity, adverse pharmacological effect, or abnormal behavior based on inhalation toxicity was observed. Conclusions: The consideration of toxicity of Nanobiocide® is one of the major key for medical application. The results obtained revealed that the Nanobiocide® may be safe using in domestic and veterinary applications

Attenuation of Withdrawal Signs, Blood Cortisol, and Glucose Level with Various Dosage Regimens of Morphine after Precipitated Withdrawal Syndrome in Mice

Morphine withdrawal usually results in unsuccessful outcomes. Despite partial benefits from alternative substances such as methadone, its use may not lead to the desired result due to the lack of mental tranquility during the withdrawal period. In this study, by means of an animal model, morphine itself was used to manage morphine dependence. Forty mice were divided into 5 groups, in which 4 groups became dependent by increasing daily doses of morphine for 7 days (15-45 mg/kg). Afterwards, the animals received morphine for 14 days by either of the following regimens: • Once daily 45 mg/kg (positive controls) • Increasing the interval (each time 6 hours longer than the previous interval) • Irregular interval in every 36, 12 and 24 hours until the 21th day • 12, 24, 36 hours decreasing doses (each time 2.5 mg/kg less than the former dosage). Negative controls received saline solution only. On day 22, total withdrawal index (TWI) was determined by injecting 3 mg/kg of naloxone. Thereafter, blood samples were taken for the measurement of cortisol and glucose levels. TWI significantly decreased in all test groups in comparison with the positive control animals (P<0.001). Cortisol levels significantly decreased when either the dosage or the administration frequencies were decreased on a regular and gradual basis (P<0.005). Blood glucose levels significantly decreased in animals that received decreasing doses of morphine (P<0.005). This study suggests that no other measures may be required in clinical practice except for changing the dosage regimen of morphine for the cessation of self-administration

Co-Exposure Effects of LPS with Various Aflatoxin B1 Doses in Isolated Perfused Rat Liver Model

Background: Activation of inflammatory cells can cause more chemicals induced-hepatotoxicity. Aflatoxin B1 (AFB1) is a fungal toxin that induces acute hepatotoxicity in humans and animals. This study was conducted to examine the effect of co-exposure LPS and various aflatoxin B1 doses on the damage hepatic parameters in isolated perfused rat liver. Methods: Thirty-two male wistar rats (250-300g) were divided to eight groups including Control and LPS; three groups with various doses of AFB1 (0.01, 0.1 and 1 ppm) and three groups with various doses of AFB1 and Lipopolysaccharide (LPS) (300 ppm). Activity of Aspartate transaminase (AST) and Alanine transaminase (ALT) were determined in perfusate. Thiobarbituric acid reactive substances (TBARS) and Glutathione (GSH) concentrations were measured in homogenate liver. Results: At two groups of AFB 1 (with LPS and without LPS) at AFB1 concentrations of 0.1 and 1 ppm, elevation of AST and ALT enzymes activity were indicated. Values of GSH in both of groups (AFB 1 with LPS and without LPS) had reduced at concentration of 1 ppm. TBARS concentrations were enhanced in AFB1 concentration of 1 ppm in both of groups (with LPS and without LPS), however in comparison between groups (with LPS and without LPS) in similar concentrations significant different did not observe (P<0.05). Conclusion: Non-injurious dose of LPS did not enhance liver susceptibility to various doses of AFB1 in perfused rat liver. This may be in part of due to extrahepatic factors, which contribute, in more liver damage