Volumen 6 (2013): Heft 2 (June 2013)

Environmental chemical exposure has been linked to numerous diseases in humans. These diseases include cancers; neurological and neurodegenerative diseases; metabolic disorders including type 2 diabetes, metabolic syndrome and obesity; reproductive and developmental disorders; and endocrine disorders. Many studies have associated the link between exposures to environmental chemicals and cardiovascular disease (CVD). These chemicals include persistent organic pollutants (POPs); the plastic exudates bisphenol A and phthalates; low molecular weight hydrocarbons (LMWHCs); and poly nuclear aromatic hydrocarbons (PAHs). Here it is reported that though the chemicals reported on differ widely in chemical properties and known points of attack in humans, a common link exists between them. All are lipophilic species that are found in serum. Environmentally induced CVD is related to total lipophilic chemical load in the blood. Lipophiles serve to promote the absorption of otherwise not absorbed toxic hydrophilic species that promote CVD.

The antioxidant and reactive-oxygen-species-scavenging activity of stobadine has been demonstrated in previous studies. Recently, chemical modification of this leading structure led to the synthesis of other pyridoindole derivatives with significantly increased intrinsic antioxidant efficacy. Further structural modifications of stobadine provided the opportunity to increase bioavailability and attenuate unwanted side effects, such as α-adrenolytic activity. The aim of the work was to evaluate the direct effect of a novel pyridoindole, SMe1EC2, on the vascular wall ex vivo. The vasomotor effect of SMe1EC2 (1×10^-8-1×10^-4 mol/l) was measured on isolated and pressurized rat cerebral and coronary arterioles using video-microscopy. The effect of SMe1EC2 (1×10^-6 and 1×10^-5 mol/l) on high potassium-, phenylephrine- or serotonin-induced contraction or acetylcholine-induced relaxation was also determined in aortic rings. We found that SMe1EC2 (1×10^-8-1×10^-4 mol/l) elicited significant dilatations in both cerebral and coronary arterioles (max dilatation: 25±8% and 18±5% respectively). Yet, SMe1EC2 (1×10^-6 and 1×10^-5 mol/l) did not influence the tone of aortic rings nor did it affect high potassium-, phenylephrine- or serotonin -induced contractions and acetylcholine-induced relaxation. Thus SMe1EC2 was able to dilate resistance arteries but did not affect aortic contractility. It is likely that SMe1EC2 does not possess α1-adrenolytic and anti-serotoninergic activity in the vascular wall.

At present, nanoparticles are beginning to influence our lives in many ways and understanding the environmental health and safety aspect of nanomaterials has become a crucial issue. The aim of the work was to assess and compare the acute toxicity of 31 different nanomaterials to fish mature individuals Danio rerio with that to fish early life stages on using evaluation of the 48- and 96- hour LC₅₀ values. A further aim was to evaluate teratogenicity of the nanoparticles tested to fish eggs. The nanoparticles tested were: 8 pure metals, 10 metal oxides, 5 other metal compounds and their mixtures, 2 silicon compounds, 3 calcium compounds, and 3 carbon compounds. Using 48-h and 96-h tests of acute toxicity (according to OECD 203), we evaluated mortality data, LC₅₀ values, occurrence of malformations, as well as hatching time. In our study, 6 kinds of nanoparticles - calcium oxide, copper, copper in the form of oxide and CuZnFe₄O₄, magnesium oxide, and nickel - caused cumulative mortality. Two kinds of nanoparticles - copper and silver - were toxic for fish with LC₅₀ values of approximately 3 mg/L. We did not observe marked differences between the 48-hour and 96-hour acute toxicity LC₅₀ values, yet the possibility to evaluate hatching time in the 96-h acute fish toxicity test seems to be an advantage against that of the 48-hour toxicity.

131-radioiodine has been widely used as an effective radionuclide for treatment of patients with thyroid diseases. The purpose of this study was to investigate the genotoxic effects of iodine-131 in human cultured lymphocytes. Whole blood samples from human volunteers were incubated with iodine-131 (10, 50, 100 μCi/1.5ml) for 2 h. The lymphocytes were mitogenically stimulated to allow for evaluation of the number of micronuclei in cytokinesis-blocked binucleated cells. At the dose 100 μCi, iodine-131 induced genotoxicity by an 8.5 fold increase in the frequency of micronuclei in human lymphocytes compared with the control group.

The possible genotoxic activity of Dichlorvos (2,2-Dichlorovinyl-O,O-dimethyl phosphate/DDVP, CAS No. 62-73-7), an organophosphorus insecticide was investigated employing three cytogenetic end points, i.e. micronucleus (MN) assay, mitotic indices (MI) and chromosome abberation (CA) analysis in vivo. The assays were carried out in hematopoietic bone marrow cells of Mus musculus at concentrations of 10, 20 and 30% of LD₅₀ for intraperitoneal (ip) administration, corresponding to 0.06, 0.08 and 0.13 mg/kg Bwt, respectively. The normal control group received single ip dose of distilled water (2 ml/100 g Bwt), while animals of the positive group were injected with cyclophosphamide, a model mutagen (40 mg/kg Bwt) under identical conditions. The animals were sacrificed 24, 48 and 72 hrs post treatment. Under the present experimental conditions, there was no evidence of significant increase of MN frequencies at any dose or sampling time in polychromatic (PCE) and normochromatic (NCE) erythrocytes. The PCE/NCE ratio was not notably affected; however, a slight depression in prolonged exposure (48, 72 hr) intervals and a slight increase at the 24 hr interval were observed. Cells with various structural chromosome aberrations were noted but no significant (p<0.05; Man-Whitney U-test) differences in the frequencies of CA or mitotic indices (p<0.05; X² test) were observed between Dichlorvos treated groups and the normal control group at doses or time intervals used. The results of the present investigation reflects a negative in vivo genotoxic potential of Dichlorvos at sublethal doses in bone marrow cells. Further studies are underway to confirm the presence or absence of genotoxic activity since compounds negative in genotoxic evaluation are susceptible of being carcinogens triggering cancer by genotoxic or non-genotoxic mechanisms.

Sertoli cell proliferation is attenuated before attaining puberty and the number is fixed in adult testes. Sertoli cells determine both testis size and daily sperm production by providing physical and metabolic support to spermatogenic cells. Polychlorinated biphenyls (PCBs) exposure disrupts functions of Sertoli cells causing infertility with decreased sperm count. On the other hand, lycopene is improving sperm count and motility by reducing oxidative stress in humans and animals. Hence we hypothesized that PCBs-induced infertility might be due to Sertoli cell apoptosis mediated by oxidative stress and lycopene might prevent PCBs-induced apoptosis by acting against oxidative stress. To test this hypothesis, animals were treated with vehicle control, lycopene, PCBs and PCBs + lycopene for 30 days. After the experimental period, the testes and cauda epididymidis were removed for isolation of Sertoli cells and sperm, respectively. We observed increased levels of oxidative stress markers (H₂O₂ and LPO) levels, increased expression of apoptotic molecules (caspase-8, Bad, Bid, Bax, cytochrome C and caspase-3), decreased anti-apoptotic (Bcl2) molecule and elevated apoptotic marker activity (caspase-3) in Sertoli cells of PCBs-exposed animals. These results were associated with decreased sperm count and motility in PCBs exposed animals. On the other hand, lycopene prevented the elevation of Sertoli cellular apoptotic parameters and prevented the reduction of sperm parameters (count and motility). The data confirmed that lycopene as an antioxidant scavenged reactive oxygen substances, prevented apoptosis, maintained normal function in Sertoli cells and helped to provide physical and metabolic support for sperm production, thereby treating infertility in men.

Arsenic contamination of groundwater has been previously reported in Ghopuz, a village located in the Northwest of Iran. Samples were taken from consuming and irrigation water and plants of the region for chemical analysis. A seven-year old ewe, which had lived in and fed a lifelong at the same place, with clinical signs such as weakness, wasting and inappropriate integument was necropsied. Grossly, buccal erosion, stomatitis, cutaneous ulcers and serous atrophy of fat deposits were observed. Rumen contents, wool and several tissue samples were obtained for toxicological and histopathological examinations. Mean arsenic concentration in the spring water, irrigation water and grass/algae were 70.11, 48.74 and 141.85 ppb (μg/kg), respectively. Arsenic levels were 486.73, 247.94, 127.92, 125.97 and 231.24 ppb in wool, skin, rumen contents, liver and kidney, respectively. Microscopic study revealed hyperemia and heavy parasitic infestation of the abomasal wall. Hyperemia and regeneration of renal tubule epithelia were observed in kidneys and hyperkeratosis, suppurative deep dermatitis and paniculitis were found in skin. Periacinar fibrosis and a poorly differentiated cholangiocarcinoma were seen in liver. In pancreas, reduced cell density of islands of Langerhans was noticeable. In the central nervous system, perineuronal and perivascular edema, ischemic changes in gray matter neurons, and microcavitation of white matter were present. Our findings confirmed chronic arsenic toxicosis in small ruminants in this region. It can be concluded that long-term consumption of arsenic contamined water and forage may be associated with chronic arsenic poisoning in domestic animals and human beings, with consequent neoplastic disease and induction of diabetes in this region.

The aim of the present study was to evaluate local irritant effects to rabbit skin following a single application of test samples of non-sterile polyamide non-absorbable surgical sutures POLYMED ®. The polar and nonpolar extracts were prepared by using saline solution and olive oil, respectively, after sinking the materials tested (2.0 g) in 10 ml of the corresponding liquid. Incubation was carried out at the temperature of 37°C for 72 h. The saline solution and pure olive oil, which had no contact with the materials tested, were used as negative control samples and were incubated under the same conditions as above. Assessments of the extracts from each material were conducted on 2 albino rabbits of the New Zealand breed. On the back of each animal, 5 intracutaneous injections of the extract tested and 5 injections of the control solution, each of 0.2 ml, were carried out. The degree of irritation was scored at 4, 24, 48, 72 hours after injection and no skin changes were found. The intracutaneous irritation index (III) was calculated and yielded 0.0. Hence it was concluded that under the experimental conditions the extracts of the material tested, i.e. non-sterile polyamide non-absorbable surgical sutures POLYMED ®, were ‘non-irritant’ to the skin of rabbits when compared with the respective control groups. The experimental procedure was conducted according to ISO10993-10.