Toxicology and Industrial Health

Ali, Shaheen Jafri; Rajini, Padmanabhan Sharda

doi: 10.1177/0748233714547733pmid: 25227224

Our earlier study had shown that low concentrations of monocrotophos (MCP) elicited dopaminergic features of Parkinson’s disease (PD) in the nematode Caenorhabditis elegans. In the present study, the effect of low doses of MCP on the striatal dopaminergic neurons was investigated using the mouse model system. MCP was initially screened for its ability to cause any neurobehavioral deficits and alterations in the dopaminergic system in Swiss albino mice, aged 8 weeks and weighing 25–30 g, with repeated doses at 0.3 and 0.6 mg/kg body weight (b.w.)/day for 7 days and 30 days. Mice were treated with four intraperitoneal injections for every 2 h with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at the dosage of 14 mg/kg b.w. MCP was administered to these mice at the above-mentioned doses for 7 days. Mice administered with MCP alone revealed a significant (p < 0.05) reduction in the dopamine (DA) content at both 7 and 30 days and showed a significant (p < 0.05) increase in neurobehavioral deficits. Interestingly, when MCP was administered for 7 days to MPTP-treated mice, further significant decrease in both DA content and increase in neurobehavioral deficits were apparent. The extent of reactive oxygen species and lipid peroxidation were markedly increased, while the ratio of reduced to oxidized glutathione levels were significantly decreased (p < 0.05) in the treated mice as compared to the control. Significant histopathological alterations and a marked reduction in the number of tyrosine hydroxylase positive cells were evident in striatum of mice treated with higher doses of MCP. These changes were comparable to that seen in mice treated with MPTP and post-administered lower doses of MCP. Our findings suggest that MCP per se has the propensity to induce pathological changes in the dopaminergic neurons as well as augment the degeneration in a compromised nigrostriatal system such as that in PD.

Liao, Peng; Li, Yunhu; Li, Hongyang; Liu, Wensen

doi: 10.1177/0748233714549066pmid: 25227225

Apoptosis triggered by ricin toxin (RT) has previously been associated with certain cellular organellar compartments, but the diversity in the composition of the organellar proteins remains unclear. Here, we applied a shotgun proteomics strategy to examine the differential expression of proteins in the mitochondria, nuclei, and cytoplasm of HeLa cells treated and not treated with RT. Data were combined with a global bioinformatics analysis and experimental confirmations. A total of 3107 proteins were identified. Bioinformatics predictors (Proteome Analyst, WoLF PSORT, TargetP, MitoPred, Nucleo, MultiLoc, and k-nearest neighbor) and a Bayesian model that integrated these predictors were used to predict the locations of 1349 distinct organellar proteins. Our data indicate that the Bayesian model was more efficient than the individual implementation of these predictors. Additionally, a Biomolecular Interaction Network (BIN) analysis was used to identify 149 BIN subnetworks. Our experimental confirmations indicate that certain apoptosis-related proteins (e.g. cytochrome c, enolase, lamin B, Bax, and Drp1) were found to be translocated and had variable expression levels. These results provide new insights for the systematic understanding of RT-induced apoptosis responses.

Mansour, Sameeh Abdel-Kader; Gamet-Payrastre, Laurence

doi: 10.1177/0748233714548207pmid: 25234640

Pesticides are omnipresent in environment, water, fruits, and vegetables and are considered as risk factors for human health. Consumers are mainly exposed to pesticides through diet, and the main question to be answered concerns the impact of such exposure on health. In this study, we developed a mouse model to mimic consumer exposure. During gestation and lactation periods, the experimental mouse dams (M) received one of the following treatments: (a) diet-free of pesticides; (b) diet enriched with chlorpyrifos (CPF; 44.0 μg kg−1); c) diet + oral vitamin E (vit. E; α-tocopherol; 200 mg/kg/mouse); and (d) diet enriched with CPF (44.0 μg/kg + oral vit. E (200 mg/kg/mouse). At weaning, pups (P) and dams were killed, and organs as well as blood samples were collected. Compared with control results, CPF induced alteration of measured parameters (e.g. organ weight, alkaline phosphatase, urea, malondialdehyde, superoxide dismutase, and cholinesterase) either in mouse dams or in their offspring. Also, CPF induced histological impairment in kidney, liver, and ovary. Administration of vit. E in conjunction with CPF clearly alleviated deviation of these parameters than those of control ones. In conclusion, a dietary exposure of mice during gestation and lactation to low dose of CPF led to significant changes in the mother but also in the weaned animals that have not been directly exposed to this pesticide. These biological and histological modifications could be reversed by an oral supplementation of vit. E.

Ozsoy, Ozlem; Aras, Sinem; Ozkan, Ayse; Parlak, Hande; Aslan, Mutay; Yargicoglu, Piraye; Agar, Aysel

doi: 10.1177/0748233714552688pmid: 25342669

Sulfite, commonly used as a preservative in foods, beverages, and pharmaceuticals, is a very reactive and potentially toxic molecule which is detoxified by sulfite oxidase (SOX). Changes induced by aging may be exacerbated by exogenous chemicals like sulfite. The aim of this study was to investigate the effects of ingested sulfite on visual evoked potentials (VEPs) and brain antioxidant statuses by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. Brain lipid oxidation status was also determined via thiobarbituric acid reactive substances (TBARS) in normal- and SOX-deficient aged rats. Rats do not mimic the sulfite responses seen in humans because of their relatively high SOX activity level. Therefore this study used SOX-deficient rats since they are more appropriate models for studying sulfite toxicity. Forty male Wistar rats aged 24 months were randomly assigned to four groups: control (C), sulfite (S), SOX-deficient (D) and SOX-deficient + sulfite (DS). SOX deficiency was established by feeding rats with low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg kg−1 day−1) was given by gavage. Treatment continued for 6 weeks. At the end of the experimental period, flash VEPs were recorded. Hepatic SOX activity was measured to confirm SOX deficiency. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with the normal rats. The activity of SOX in deficient rats was thus in the range of humans. There was no significant difference between control and treated groups in either latence or amplitude of VEP components. Brain SOD, CAT, and GPx activities and brain TBARS levels were similar in all experimental groups compared with the control group. Our results indicate that exogenous administration of sulfite does not affect VEP components and the antioxidant/oxidant status of aged rat brains.

Rahmanpour, Shirin; Ashtiyani, Seyede Masoumeh Lotfi; Ghorghani, Nasrin Farzaneh

doi: 10.1177/0748233714554410pmid: 27353297

The main aim of this study was to biomonitor mercury (Hg), arsenic (As), cadmium (Cd), lead (Pb) and copper (Cu) concentrations in the Arvand River using Heteropnestis fossilis and Parasesarma persicum. Comparison of heavy metals among the stations indicated that the concentrations of Hg, As, Cd, Cu and Pb in sediment samples were apparently different among the stations. The results of linear regression analyses showed that there were significant correlations (p < 0.05) between Hg, As and Pb elements in sediment and hepatopancreas of P. persicum and between As in sediment and liver of H. fossilis. These findings showed that P. persicum could be considered as a biomonitor of Hg, As and Pb and H. fossilis as a biomonitor of As contamination in sediment of the Arvand River.

Çamur, Derya; Güler, Çağatay; Vaizoğlu, Songül Acar; Özdilek, Betül

doi: 10.1177/0748233714555393pmid: 27353298

An increase in enviromental pollution may lead to mercury toxicity of fish origin due to the accumulative nature of methylmercury in fish. The main sources of human exposure to organic mercury compounds are contaminated fish and other seafoods. This descriptive study was planned to determine mercury levels in anchovy and in hair samples from individuals with different fish consumption habits, and to evaluate those individuals in terms of toxic effects. For that purpose, we analyzed 100 anchovies from the Black Sea and 100 anchovies from the Sea of Marmara, and assessed 25 wholesale workers in fish markets and 25 cleaning firm employees from both Ankara and Istanbul. Mercury levels in samples were measured using a cold vapor atomic absorption spectrophotometer. Participants were examined neurologically and mini mental state examination was applied to evaluate their cognitive functions. Mercury levels in fish were found to be below the national and international permitted levels. There was no statistically significant relation between mercury levels and the sea from which fish were caught. Hair mercury levels for all participants were within permitted ranges. However, hair mercury levels in both cities increased significantly with amount and frequency of fish consumption. A significant correlation was determined at correlation analysis between levels of fish consumption and hair mercury levels in the fishmongers and in the entire group (r = 0.32, p = 0.025; r = 0.23, p = 0.023, respectively). Neurological examination results were normal, except for a decrease in deep tendon reflexes in some participants in both cities. There was no correlation between Standardized Mini Mental State Examination results and hair mercury levels. We conclude that establishing a monitoring system for mercury levels in fish and humans will be useful in terms of evaluating potential neurotoxic effects.

Nitha, A; Prabha, SP; Ansil, PN; Latha, MS

doi: 10.1177/0748233714552120pmid: 25415873

Hepatic fibrosis, characterized by extracellular matrix accumulation, is the common cause of chronic liver failure and is a leading cause of morbidity and mortality worldwide. The aim of the present study was to evaluate the effect of dried flowers of Woodfordia fruticosa on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rat model. Hepatic fibrosis was induced in male Wistar rats by CCl4 administration (150 μl/100 g rat weight, oral) twice a week for 10 weeks. In preventive model, administration of daily doses of methanolic extract of W. fruticosa (MEWF) at two different doses (100 mg/kg, body weight (b.w.) and 200 mg/kg, b.w.) was started 1 week before the onset of CCl4 administration and continued for 10 weeks. In curative model, MEWF at 100 and 200 mg/kg were given for last 2 weeks after the establishment of fibrosis. MEWF at a dose of 200 mg/kg was able to exert a more pronounced effect as evidenced histologically by significant reduction in fibrotic septa formation in liver tissue, immunohistochemically by abridged expression of collagen III, and also biochemically by serum and tissue antioxidant status, lipid peroxidation, and hydroxyproline level. Liquid chromatography–mass spectrometry analysis revealed the presence of confertin, quercetin methyl ether, ellagic acid, and stigmasterol in MEWF, which could be responsible for its antifibrotic activity. These results indicate the effective protection exerted by MEWF against CCl4-induced hepatic fibrosis in a dose-dependent manner.

Razavi, Bibi Marjan; Hosseinzadeh, Hossein; Abnous, Khalil; Khoei, Alireza; Imenshahidi, Mohsen

doi: 10.1177/0748233714554941pmid: 27353299

Research has suggested that natural antioxidant, crocin, an active ingredient of saffron, may protect against diazinon (DZN)-induced toxicity. Although increased production of lipid peroxidation by DZN in rat aorta has been shown previously, the effects of DZN on oxidative stress-induced apoptosis in vascular system have not been evaluated. In this study, the effect of crocin on DZN-induced apoptosis in rat vascular system was investigated. The rats were divided into 7 groups: corn oil (control), DZN (15 mg/kg/day, gavage), crocin (12.5, 25, and 50 mg/kg/day, intraperitoneally (i.p.)) + DZN, vitamin E (200 IU/kg, i.p., 3 days a week) + DZN, and crocin (50 mg/kg/day, i.p.). The treatments were continued for 4 weeks. Levels of apoptotic (Bax, caspase 3, and caspase 9) and antiapoptotic proteins (Bcl2) were analyzed by Western blotting. Transcript levels of Bax and Bcl2 genes were determined using quantitative real-time polymerase chain reaction. Results showed DZN-induced apoptosis by activation of caspase 9 and caspase 3 and by increasing the Bax/Bcl2 ratio (both protein and messenger RNA levels). Crocin and vitamin E inhibited apoptosis induced by DZN. In summary, subchronic exposure to DZN induced caspase-mediated apoptosis, and crocin reduced the toxic effects of DZN by inhibiting apoptosis in aortic tissue.

Parsa, Maliheh; Ostad, Seyed Nasser; Moogahi, Seyed Mohammad Hossein Noori; Bayat, Mohammad; Ghahremani, Mohammad Hossein

doi: 10.1177/0748233714555153pmid: 27353300

Objective:Polycyclic aromatic hydrocarbons (PAHs) are potent environmental pollutants. Benzo[α]pyrene (B[α]P) is the major compound of PAHs that acts by activating aryl hydrocarbon receptor (AhR) in cells. B[α]P is a known carcinogen and an immunotoxicant; however, its role with regard to nuclear factor of activated T cell (NFAT) pathway is unclear. AhR and NFAT signaling pathways have common roles in pathological functions in immunotoxicity and lung cancer. In this study, the effect of AhR activation on expression and signaling cross talk of AhR and NFATc1 pathways in mouse lung tissue has been investigated.Methods:Swiss albino mice were randomly allocated to five groups and administered with cyclosporin A (CsA) and B[α]P for seven constitutive days. Animals were then killed, and lung tissues were obtained after washing the whole blood. Paraffin-embedded blocks were prepared, and 5 µm sections were cut for histopathological and immunohistochemical assessments. The results were scored by observer and digitally analyzed using ImageJ software.Results:Our data showed that CsA administration resulted in a significant reduction of AhR expression. This effect was partly blocked in mice coadministrated with B[α]P and CsA. NFATc1 expression was also reduced in CsA-treated animals. Furthermore, CsA inhibited the pathological effects of B[α]P in mouse lung tissue.Conclusion:AhR expression is dependent on NFATc1 activation, and NFATc1 inhibition remarkably decreases AhR expression. However, it seems that total expression of NFATc1 is not dependent on AhR expression or activation. Moreover, CsA can prevent B[α]P-induced lung tissue damage, and it remarkably decreases NFATc1 expression. The results from this study point toward the molecular interactions of AhR and NFATc1 activation in lung tissue and the benefit of CsA treatment in B[α]P-induced lung damage.

Nisar, Muhammad; Ali, Sajid; Muhammad, Naveed; Gillani, Syed N; Shah, Muhmmad R; Khan, Haroon; Maione, Francesco

doi: 10.1177/0748233714555391pmid: 25501256

Rhododendron arboreum Smith. (Ericaceae), an evergreen small tree, is one of the 1000 species that belongs to genus Rhododendron distributed worldwide. In folk medicine, as various parts of this plant exhibit medicinal properties, it is used in the treatment of different ailments.The present study was designed to evaluate the potential anti-inflammatory and antinociceptive effects of methanolic extract of R. arboreum bark, followed by activity-guided fractionation of n-hexane, n-butanol, chloroform, ethyl acetate and aqueous fractions.The ethyl acetate fraction (200 mg/kg i.p.) showed the maximum analgesic effect (82%) in acetic acid-induced writhing, followed, to a less extent, by crude extract and chloroform fraction both at a dose of 200 mg/kg i.p. (65.09% and 67.89%, respectively). In carrageenan-induced mouse paw oedema, the crude extract and its related fractions displayed in a dose-dependent manner (50–200 mg/kg i.p.) an anti-inflammatory activity for all time-courses (1–5 hrs). For the active extract/fractions (200 mg/kg i.p.), the maximum effect was observed 5 h after carrageenan injection. These evidences were also supported by invitro lipoxygenase inhibitory properties. In conclusion, R. arboreum crude methanolic extract and its fractions exhibited anti-inflammatory and antinociceptive effects. For these reasons, this plant could be a promising source of new compounds for the management of pain and inflammatory diseases.