Toxicology and Industrial Health

Yang, Jianying ;Zhang, Yongfa ;Jing, Aihua ;Ma, Kaiwang ;Gong, Qiang ;Qin, Cuili

doi: 10.1177/0748233712464810pmid: 23108506

Objective: To investigate the effects of T-2 toxin on testosterone biosynthesis in mouse Leydig cells. Methods: Leydig cells isolated from clean and healthy Kunming male mice, whose concentration was adjusted to 5 × 105/mL and the purity identified by the modified 3β-hydroxysteroid dehydrogenase staining method, were used to establish a primary Leydig cell culture model. Blank control group (treated with 0 ng/mL human chorionic gonadotropin (hCG) and 0 mol/L T-2 toxin), inductive control group (treated with 10 ng/mL hCG and 0 mol/L T-2 toxin), low-dose T-2-toxin-exposure group (treated with 10 ng/mL hCG and 10−9 mol/L T-2 toxin), middle-dose T-2 toxin-exposure group (treated with 10 ng/mL hCG and 10−8 mol/L T-2 toxin) and high-dose T-2-toxin-exposure group (treated with 10 ng/mL hCG and 10−7 mol/L T-2 toxin) were designed. The testosterone level was measured after 24 h incubation. Results: After 24 h culture in liquid medium containing serum, the fresh isolated Leydig cells grew well and the purity exceeded 90%. By inducing 10 ng/mL hCG, the testosterone level of Leydig cells increased significantly and the difference compared with the blank control was of statistical sense. Compared with the inductive control group, the testosterone level of Leydig cells decreased, and the difference was of statistical sense in all T-2-toxin-exposure groups. Furthermore, the decrease was due to the increase in the dosage of T-2 toxin. Conclusions: T-2 toxin can directly decrease the testosterone biosynthesis in the primary Leydig cells derived from the mouse testis.

Çolak, Suat ;Geyikoğlu, Fatime ;Aslan, Ali ;Deniz, Gülşah Yıldız

doi: 10.1177/0748233712466130pmid: 23114377

The prevalence of diabetes mellitus in the world is steadily increasing. Oxidative stress contributes to the development of diabetic complications, including diabetic haematological changes. Lichens are used as food supplements and are also used as possible natural antioxidant, antimicrobial and anticancer agents. We hypothesized that antioxidant activity of lichens may decrease hyperglycaemia-induced oxidative stress and prevent the development of diabetic complications, including abnormality in haematological condition. Therefore, the effects of Cetraria islandica water extract (CIWE) and Pseudevernia furfuracea water extract (PFWE) on the haematological parameters of rats with type 1 DM were investigated for the first time in the present study. Control Sprague-Dawley or streptozotocin (STZ)-induced diabetic rats were either untreated or treated with water lichen extracts (5–500 mg/kg body weight (bw)/day) for 2 weeks, starting at 72 h after STZ injection. On day 14, animals were anaesthetized and haematological and metabolic parameters were determined between control and experimental groups. In addition, the total oxidative stress (TOS), a specific indicator of oxidative stress, and the total antioxidant capacity (TAC) were measured by biochemical studies. In diabetic rats, CIWE of 250–500 mg/kg bw dose showed more prominent results when compared with doses of PFWE for TAC. The results obtained in the present study suggested that the antioxidant activities of lichens might be the possible reason behind the observed antihaematological status. However, the protective effect of lichen extracts were inadequate on diabetes-induced microcytic hypochromic anaemia. In addition, the extracts have no effect on metabolic complications. Our experimental data showed that high doses of CIWE and PFWE alone have no detrimental effect on blood cells and TOS status of plasma. Hence, they are safe and suitable for different administration routes.

Hasgul, Rukiye ;Uysal, Sema ;Haltas, Hacer ;Akyol, Sumeyye ;Yuksel, Yasemin ;Gurel, Ayse ;Armutcu, Ferah

doi: 10.1177/0748233712466134pmid: 23114375

The exposure of gastric mucosa to damaging factors, such as ethanol and some therapeutic drugs, produces pathological changes: inflammatory process, hemorrhagic erosions and even acute ulcers. Ankaferd blood stopper (ABS) comprises a standardized mixture of five different plant extracts. The purpose of our present investigations is to explain the participation of reactive oxygen species in acute gastric mucosal damage by acetylsalicylic acid (ASA) and the effects of new hemostatic agent ABS. Experiments were carried out on 23 male Wistar rats. To assess gastric mucosal damage, biochemical and histopathological data were used. The colorimetric assays were used to determine the malondialdehyde (MDA) and superoxide dismutase (SOD) activity. The level of myeloperoxidase (MPO) activity, the level of nitric oxide (NO) and the proinflammatory cytokine tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay technique. We demonstrated that the biological effects of ROS were estimated by measuring the tissue and plasma levels of MDA, the products of lipid peroxidation, as well as the activity of SOD and the scavenger of ROS produced by ASA in the experiment group. Moreover, it was found that MPO activity as well as NO and TNF-α levels also demonstrated significant improvement by ABS treatment. The pathogenesis of experimental ASA-induced mucosal damage in rat stomach includes the generation of ROS that seems to play an important role, due to the generation of lipid peroxides, accompanied by the impairment of antioxidative enzyme activity of cells. ABS appeared to attenuate the oxidative and inflammatory changes caused by ASA-induced gastric mucosal damage in rats.

Tarik, Ocak ;Zeynep, Ocak ;Hasan, Dogan ;Mustafa, Uzkeser ;Ahmet, Yesilyurt ;Mevlit, Ikbal ;Şahin, Aslan

doi: 10.1177/0748233712466131pmid: 23114376

Aim: Carbon monoxide (CO) intoxication can be serious and is reported to be the cause of more than half of all fatal intoxications. In this study, we aimed to identify its genotoxic effects based on sister chromatid exchange (SCE). Materials and methods: CO-poisoned patients presented to the emergency services department were identified. Their demographic characteristics, vital findings, laboratory markers, source of CO gas, risk factors, and smoking habits were recorded. The genotoxic effect was assessed using the SCE method. Results: A total of 38 patients were recruited. Their ages ranged from 16–64 years (mean: 29.79 ± 10.92 years). In all the cases, the source of CO gas was a flash heater. The mean carboxyhemoglobin (COHb) level was 25.05 ± 7.15%. Of all the patients, 12 (31.6%) had a the Glasgow Coma Scale (GCS) scores of less than 15, and an important negative correlation was found between the GCS and COHb level (r = −0.825; p < 0.001). Genotoxicity investigations revealed a significantly higher SCE frequency among patients with high COHb levels compared with that of control subjects with physiological COHb levels (p < 0.001). However, no correlation between increased SCE frequency and COHb level was found (r = 0.16; p = 0.34). Conclusion: CO poisoning was shown to result in genotoxicity via an increase in the frequency of SCE. This study is the first to demonstrate a genotoxic effect of CO independent of other chemicals.

Shi, Yu-Qin ;Chen, Xin ;Dai, Juan ;Jiang, Zhong-Fa ;Li, Ning ;Zhang, Ben-Yan ;Zhang, Zhi-Bing

doi: 10.1177/0748233712466129pmid: 23160383

Formaldehyde is a major industrial chemical and has been extensively used in the manufacture of synthetic resins and chemicals. Numerous studies indicate that formaldehyde can induce various genotoxic effects in vitro and in vivo. A recent study indicated that formaldehyde impaired antioxidant cellular defences and enhanced lipid peroxidation. Selenium is an important antioxidant. We hypothesized that reactive oxygen species (ROS) and lipid peroxidation are involved in formaldehyde-induced genotoxicity in human lung cancer cell line, A549 cell line. To test the hypothesis, we investigated the effects of selenium on formaldehyde-induced genotoxicity in A549 cell lines. The results indicated that exposure to formaldehyde showed the induction of DNA–protein cross-links (DPCs). Formaldehyde significantly increased the malondialdehyde levels and decreased the activities of superoxide dismutase and glutathione peroxidase. In addition, the activations of necrosis factor-κB (NF-κB) and activator protein 1 (AP-1) were induced by the formaldehyde treatment. The pretreatment with selenium counteracted the formaldehyde-induced oxidative stress, ameliorated DPCs and attenuated the activation of NF-κB and AP-1 in A549 cell lines. All the results suggested that the pretreatment with selenium attenuated the formaldehyde-induced genotoxicity through its ROS scavenging and anti-DPCs effects in A549 cell lines.

Pirinççioğlu, Mihdiye ;Kızıl, Göksel ;Kızıl, Murat ;Kanay, Zeki ;Ketani, Aydın

doi: 10.1177/0748233712464809pmid: 23160382

Most pomegranate (Punica granatum Linn., Punicaceae) fruit parts are known to possess enormous antioxidant activity. The present study was carried out to determine the phenolic and flavonoid contents of Derik pomegranate juice and determine its effect against carbon tetrachloride (CCl4)-induced toxicity in rats. Animals were divided into four groups (n = 6): group I: control, group II: CCl4 (1 ml/kg), group III: CCl4 + pomegranate juice and group IV: CCl4 + ursodeoxycholic acid (UDCA). Treatment duration was 4 weeks, and the dose of CCl4 was administered once a week to groups II, III and IV during the experimental period. CCl4-treated rats caused a significant increase in serum enzyme levels, such as aspartate aminotransferase, alanine aminotransferase and total bilirubin, and decrease in albumin, when compared with control. Administration of CCl4 along with pomegranate juice or UDCA significantly reduces these changes. Analysis of lipid peroxide (LPO) levels by thiobarbutiric acid reaction showed a significant increase in liver, kidney and brain tissues of CCl4-treated rats. However, both pomegranate juice and UDCA prevented the increase in LPO level. Histopathological reports also revealed that there is a regenerative activity in the liver and kidney cells. Derik pomegranate juice showed to be hepatoprotective against CCl4-induced hepatic injury. In conclusion, present study reveals a biological evidence that supports the use of pomegranate juice in the treatment of chemical-induced hepatotoxicity.

Noureldeen, Amani FH ;Qusti, Safaa Y ;Khoja, Gelan MS

doi: 10.1177/0748233712466133pmid: 23188649

Background: A variety of HIV-related endocrine dysfunctions including adrenal, gonadal and thyroid disorders have been reported. We aimed to compare between the markers of thyroid function in newly diagnosed HIV-infected patients and healthy volunteers as a control group. The prevalence of the thyroid abnormalities in HIV-infected patients was assessed and the levels of thyroid autoantibodies were also determined. Methods: A total of 100 newly diagnosed HIV-infected patients having a CD4 cell count of 180–350 cells/mm3 were enrolled in the study. Same number of healthy volunteers were also included for comparison. Measurements of thyroid function tests including thyroid-stimulating hormone (TSH), free thyroxin and free triiodothyronine levels beside thyroid autoantibodies, including antithyroglobulin (ATBG) and antithyroid peroxidase (ATPO), were carried out for all patients and volunteers. Results: In total, 70% of HIV-infected patients had normal thyroid function tests when compared with control individuals, while 30% of HIV-infected patients had abnormal thyroid function. Of the 30 cases, 11 cases had abnormal TSH values, with increased TSH predominant (7% of HIV cases) than decreased TSH (4% of patients) values. Incidence of thyroid abnormalities ranging from hypothyroidism (subclinical and overt: 6% and 1%, respectively) to hyperthyroidism (2%) and nonthyroidal illness (9%) were estimated in HIV-infected patients. The values of thyroid autoantibodies were almost normal in HIV-infected patients, except the three cases presented with elevated ATBG, indicating that thyroid abnormalities were not due to elevated ATBG and ATPO. Conclusions: Thyroid hormones are of great importance and due to high prevalence of thyroid function abnormality, it is recommended that thyroid function tests should be monitored in all HIV-infected patients before starting the treatment.

Yilmaz, Serkan ;Ünal, Fatma ;Yüzbaşıoğlu, Deniz ;Çelik, Mustafa

doi: 10.1177/0748233712466132pmid: 23188648

In vitro genotoxic effects of antioxidant additives, such as citric acid (CA) and phosphoric acid (PA) and their combination, as well as antimicrobial additives, such as benzoic acid (BA) and calcium propionate (CP), on human lymphocytes were determined using alkaline single-cell gel electrophoresis. There was a significant increase in the DNA damage in human lymphocytes after 1 h of in vitro exposure to CA, PA, BA and CP (200, 25–200, 50–500, 50–1000 μg/mL, respectively). The combination of CA and PA significantly increased the mean tail intensity at all the concentrations used (25–200 μg/mL) and significantly increased the mean tail length mainly after higher concentrations (100 and 200 μg/mL). Data in this study showed that the concentrations of food additives used induce DNA damage and PA was the most genotoxic and CA was less genotoxic additives among them.

Akdogan, Mehmet ;Kisioglu, Ahmet Nesimi ;Ciris, Metin ;Koyu, Ahmet

doi: 10.1177/0748233712466136pmid: 23188651

In a study on villagers settled on the outskirts of the Taurus Mountains and whose source of living is thyme, it was revealed that the villagers excessively consumed thyme by adding it to their tea and many of their foods; high incidences of anemia was found among these villagers. In this study, 42 male adult Wistar albino rats weighing 200–250 g were used. The rats were divided to six equal groups as follows: control, cholesterol (Chol), 80 mg/kg Origanum onites Labiatae (OOL), 80 mg/kg Thymbra spicata Labiatae (TSL), 80 mg/kg Satureja cuneifolia Labiatae (SCL), and 160 mg/kg TSL, and each group consisted of seven rats. The control group was fed with normal pellet feed. The Chol group and all the other groups, except for the control group, were fed with 2% cholesterol-containing pellet feed. Physiological serum of 4 ml was given to the control and Chol group, wheile 80 mg/kg of thymes tea was given to the OOL group, TSL group, and SCL group, and 160 mg/kg of thymes tea was given to the TSL group by means of a gavage for 30 days. In the blood samples, the hematologic parameters and the biochemical parameters of serum glucose, blood urea nitrogen, creatinine, total protein, albumin, iron (I), total iron-binding capacity, aminotransferase aspartate, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglyceride, and oxidized LDL levels were examined. The kidney and liver tissues were examined histopathologically. The results of the study showed that different types of thymes had an antihypercholesterolemic effect. In addition to the anemic effect detected in group TSL and the mild granular degeneration found in the liver of 80 mg/kg SCL group, distinct granular degeneration was observed in 160 mg/kg TSL group.

Nema, Neelesh K ;Maity, Niladri ;Sarkar, Birendra K ;Mukherjee, Pulok K

doi: 10.1177/0748233712468015pmid: 23222691

Traditionally, the herbal drugs are well established for their therapeutic benefits. Depending upon their geographical sources sometimes the trace and heavy metals’ content may differ, which may lead to severe toxicity. So, the toxicological and safety assessment of these herbal drugs are one of the major issues in recent days. Eight different plant species including Aloe vera, Centella asiatica, Calendula officinalis, Cucumis sativus,Camellia sinensis, Clitoria ternatea, Piper betel and Tagetes erecta were selected to determine their heavy and trace metals content and thereby to assure their safer therapeutic application. The trace and heavy metals were detected through atomic absorption spectrometry analysis. The selected medicinal plant materials were collected from the local cultivated regions of West Bengal, India, and were digested with nitric acid and hydrochloric acid as specified. Absorbance was measured through atomic absorption spectrometer (AA 303) and the concentration of different trace and heavy metals in the plant samples were calculated. The quantitative determinations were carried out using standard calibration curve obtained by the standard solutions of different metals. The contents of heavy metals were found to be within the prescribed limit. Other trace metals were found to be present in significant amount. Thus, on the basis of experimental outcome, it can be concluded that the plant materials collected from the specific region are safe and may not produce any harmful effect of metal toxicity during their therapeutic application. The investigated medicinal plants contain trace metals such as copper (Cu), chromium (Cr), manganese (Mn), iron (Fe) and nickel (Ni) as well as heavy metals such as arsenic (As), lead (Pb) and mercury (Hg), which were present within the permissible limit.