Toxicology International : 2011 - 18(2)

Mechanisms pertaining to arsenic toxicity

Amrit Pal Singh — Fri,26 Aug 2011

Amrit Pal Singh, Rajesh Kumar Goel, Tajpreet Kaur

Toxicology International 2011 18(2):87-93

Arsenic is an environmental pollutant and its contamination in the drinking water is considered as a serious worldwide environmental health threat. The chronic arsenic exposure is a cause of immense health distress as it accounts for the increased risk of various disorders such as cardiovascular abnormalities, diabetes mellitus, neurotoxicity, and nephrotoxicity. In addition, the exposure to arsenic has been suggested to affect the liver function and to induce hepatotoxicity. Moreover, few studies demonstrated the induction of carcinogenicity especially cancer of the skin, bladder, and lungs after the chronic exposure to arsenic. The present review addresses diverse mechanisms involved in the pathogenesis of arsenic-induced toxicity and end-organ damage.

Ameliorative effects of Tinospora Cordifolia root extract on histopathological and biochemical changes induced by Aflatoxin-B 1 in mice kidney

Rekha Gupta — Fri,26 Aug 2011

Rekha Gupta, Veena Sharma

Toxicology International 2011 18(2):94-98

The present study was planned to investigate the ability of the Tinospora cordifolia to scavenge free radicals generated during aflatoxicosis. A total no. of 48 male Swiss albino mice (30 ± 5 g) were exposed to Aflatoxin B 1 (AFB 1 ) (2 μg/30 g b.wt, orally) either individually or in combination with T. cordifolia (50, 100, 200 mg/kg, orally) once daily for 25 days. AFB 1 exposure led to significant rise in thiobarbituric acid reactive substances (TBARS) and fall in superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), ascorbic acid, and protein content. T. cordifolia was found to show protective effect by lowering down the content of TBARS and enhancing the GSH, ascorbic acid, protein, and the activities of antioxidant enzymes viz., SOD, CAT, glutathione peroxidase, GST, and GR in kidney. Histopathological analysis of kidney samples also confirmed the protective values and antioxidant activity of ethanolic extract of herb. T. cordifolia showed protection against aflatoxin-induced nephrotoxicity due to the presence of alkaloids such as a choline, tinosporin, isocolumbin, palmatine, tetrahydropalmatine, and magnoflorine.

Chronic fluoride toxicity and myocardial damage: Antioxidant offered protection in second generation rats

Mahaboob P Basha — Fri,26 Aug 2011

Mahaboob P Basha, NS Sujitha

Toxicology International 2011 18(2):99-104

This experiment was designed to investigate the extent of peroxidative changes and histological alterations in the myocardium of rats exposed to high fluoride for two generations, in addition to ameliorative role of selenium and vitamin E on the above indices. Adult albino Wistar rats were given fluoride through drinking water (200 ppm F) and maintained subsequently for two generations, while they were exposed to fluoride throughout the experiment. Fluoride treatment significantly increased the lipid peroxidation and decreased the activity of antioxidant enzymes, viz., catalase, superoxide dismutase, and glutathione level in auricle and ventricle regions of the heart. Decreased feed and water consumption, organ somatic index and marginal drop in body growth rate were observed. Decreased antioxidant enzymes and increased malondialdehyde levels might be related to oxidative damage that occurs variably in the myocardium of rats. Biochemical changes were supported by the histological observations, which also revealed that chronic exposure to fluoride causes damage to the myocardium. Results of this study can be taken as an index of cardio-toxicity in rats exposed to water fluoridation. Further, oral supplementation of selenium and vitamin E not only inhibited oxidative stress but also enhanced the activities of antioxidant enzymes. Administration of antioxidants during fluoride exposure significantly overcame cardiac fluoride toxicity and therefore may be a therapeutic strategy for fluorotic victims.

Effect of Trans-resveratrol on rotenone-induced cytotoxicity in human breast adenocarcinoma cells

MA Siddiqui — Fri,26 Aug 2011

MA Siddiqui, Q Saquib, M Ahamed, J Ahmad, AA Al-Khedhairy, FM Abou-Tarboush, J Musarrat

Toxicology International 2011 18(2):105-110

Rotenone, a botanical insecticide is known to cause apoptosis in various cell types. Trans-resveratrol, a natural phytophenol present in red grapes and wine, is also well documented for its antioxidant, anti-inflammatory, anti-mutagenic, and anticarcinogenic activities. Therefore, the present investigations were carried out to assess the protective effect of trans-resveratrol against rotenone-induced cell death in human breast adenocarcinoma (MCF-7) cells. MCF-7 cells were exposed with various concentrations of rotenone for 24 h, and the loss in percent cell viability was evaluated by MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] and neutral red uptake (NRU) assays. A significant decrease in percent cell viability in MCF-7 cells was observed at 50 μM and above concentrations of rotenone, as compared to untreated control. Furthermore, various concentrations (5, 10, and 25 μM) of trans-resveratrol were used to see its protective role on cell viability in rotenone-induced cell death in MCF-7 cells. Pre- or post- treatment of trans-resveratrol for 24 h was given to the cells. The data exhibited a significant dose dependent increase in the percent cell viability under pre- and post-treatment conditions. However, post-treatment of trans-resveratrol for 24 h after rotenone exposure to the cells was relatively less effective. Overall, the results suggest that trans-resveratrol significantly protects MCF-7 cells from rotenone-induced cell death. This model can be used as an effective and economical alternative to animal models for screening the antioxidant activity of a variety of natural compounds/drugs.

Identification of limiting factors for the optimum growth of Fusarium oxysporum in liquid medium

Shilpi Srivastava — Fri,26 Aug 2011

Shilpi Srivastava, Neelam Pathak, Prachi Srivastava

Toxicology International 2011 18(2):111-116

Fusarium oxysporum is a highly ubiquitous species that infects a wide range of hosts causing various diseases such as vascular wilts, yellows, rots, and damping-off. Despite the immense economic significance of this phytopathogen, few workers have reported growth studies in this genus in submerged culture. In the present study, several parameters such as change in media pH, biomass, pattern of substrate utilization, viability of the fungal cells, and protein content were observed over a period of time. The fungal biomass increased at a slow rate for the initial 48 h and thereafter increased at an exponential rate. However, after about 8 days the rapid growth stabilized and the trend became more toward stationary phase. The concentration of glucose in the liquid media decreased rapidly up to the initial 4 days, followed by a slow decrease. The pH of the medium gradually decreased as the fungal growth progressed, the reduction being more pronounced in the initial 48 h. This study would be of immense importance for utilization of F. oxysporum for diverse applications because we can predict the growth pattern in the fungus and modulate its growth for human benefit.

Serum creatine phosphokinase: A probable marker of severity in organophosphorus poisoning

Kuntal Bhattacharyya — Fri,26 Aug 2011

Kuntal Bhattacharyya, Sibaji Phaujdar, Rathindranath Sarkar, Omar S Mullick

Toxicology International 2011 18(2):117-123

Organophosphorus (OP), the commonest agent for poisoning in India due to its easy availability, acts by inhibiting acetylcholinesterase at muscarinic and nicotinic receptors. Erythrocyte cholinesterase (EchE) and plasma cholinesterase (PchE) are reduced in OP poisoning, but their estimation is costly and not regularly performed. There are emerging options for new cheaper biochemical markers in relation to OP poisoning. Serum level of creatine phosphokinase (CPK) is often found to be elevated in OP poisoning. This study was conducted to see if CPK may be used as an alternative of cholinesterase levels in blood to assess the severity of OP poisoning. This was a prospective and observational study. Sixty-three patients of OP poisoning without any prior treatment, presenting within 6 hours, were selected and their clinical severity was categorized according to Peradeniya organophosphorus poisoning (POP) scale. Level of serum CPK, blood EchE and pH were measured following admission, and total dose of atropine (mg) until the final clinical outcome (complete recovery or death) was calculated. Student's t-test and Pearson's correlation coefficient was used for the assessment of statistical significance. According to POP scale, clinical severity was mild (score 0-3) in 17 (27%), moderate (score 4-7) in 32 (50.8%) and severe (score 8-11) in 14 (22.2%) patients. Serum CPK, EchE level, blood pH and total atropine dose strongly correlated with clinical severity. Our study recommends serum CPK as an alternative marker.

Hepatoprotective effect of curcumin on lindane-induced oxidative stress in male wistar rats

Rambir Singh — Fri,26 Aug 2011

Rambir Singh, Poonam Sharma

Toxicology International 2011 18(2):124-129

Lindane, an organochlorine pesticide, is recognized as a major public health concern because of its potential toxic effects on human health. Its persistence in the body fluids may lead to continuous blood circulation, liver exposure and hepatotoxicity. The present study was undertaken to evaluate the possible protective role of curcumin on lindane-induced hepatotoxicity. Forty-two healthy adult male Wistar rats were divided into seven groups of six rats each. Group I was given dimethylsulfoxide. A single dose of lindane (60 mg/kg bw) was given to group II. Lindane (30 mg/kg bw) was given daily to group III for 14 days. Treatment with curcumin (100 and 200 mg/kg) was given to groups IV and V before (pretreatment) and to groups VI and VII after (post-treatment) 14 days exposure of lindane. Oxidative stress parameters and antioxidative enzymes were investigated in the liver of exposed and treated rats. A significant increase in lipid peroxidation, and decrease in glutathione level, Superoxide dismutase catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase and NADPH quinine reductase activities was observed in liver of rats exposed to lindane. Curcumin (Pre- and post-treatment) nearly normalized all these parameters. Histological alterations were also observed in the liver tissue after lindane exposure. Treatment with curcumin significantly prevented the lindane-induced histological alterations. In conclusion, curcumin has protective effect over lindane-induced oxidative damage in rat liver.

Ameliorative effect of Ocimum Sanctum on meloxicam induced toxicity in wistar rats

R Mahaprabhu — Fri,26 Aug 2011

R Mahaprabhu, AG Bhandarkar, Babu Lal Jangir, SP Rahangadale, NV Kurkure

Toxicology International 2011 18(2):130-136

An ameliorating effect of Ocimum sanctum on the toxic effect of meloxicam, a new non-steroidal anti-inflammatory drug was studied by evaluating haemato-biochemical parameters, oxidative stress, gross and histopathological changes in various organs of Wistar rats. A total of thirty-six male rats were divided in six experimental groups each comprising of six rats and numbered from G 1 to G 6 . Meloxicam toxicity was induced by oral feeding of meloxicam at 1.2 mg/kg and 2.4 mg/kg body weight in G 2 and G 3 respectively for 28 days. Group G 4 and G 5 were fed with 1.2-mg/kg body weight and 2.4-mg/kg body weight of meloxicam along with 200 mg/kg body weight of aqueous extract of Ocimum sanctum. Group G 1 serve as control while group G 6 was kept as treatment control and fed only aqueous extract of Ocimum sanctum at 200 mg/kg body weight. Clinical finding showed mild diarrhea from 23 rd day onwards in-group treated with 2.4-mg/kg body of meloxicam. Significant reduction of hemoglobin and packed cell volume (PCV) was observed in both the group treated with 1.2 mg/kg and 2.4-mg/kg body wt. of meloxicam. Ocimum sanctum could restore the hemoglobin and PCV value in-group treated with meloxicam at low dose level. Serum alkaline phosphatase, serum glutamic pyruvic transaminase, Serum glutamic oxaloacetic transaminase and total bilirubin were found elevated in meloxicam treated groups and indicated hepatotoxic activity of meloxicam. Ocimum sanctum could reduce hepatotoxic activity of meloxicam in group G4 receiving meloxicam at lower dose rate along with Ocimum sanctum failed to regulate creatinine level in meloxicam treated groups. In meloxicam toxicity elevated Lipid peroxidation values was noticed in liver and kidneys, while superoxide dismutase and glutathione did not revealed any change. Stomach and intestine revealed hemorrhagic gastroenteritis and ulcers. Perivascular necrosis with infiltration with inflammatory cells was evident in liver. Interstitial nephritis, myocardial necrosis and spongiform encephalopathy were important lesions. The Ocimum sanctum could only counteract the toxic effect of meloxicam in liver and gastrointestinal tract.

Chronic arsenicosis of cattle in West Bengal and it's possible mitigation by sodium thiosulfate

Choton K Ghosh — Fri,26 Aug 2011

Choton K Ghosh, Bakul K Datta, Suman Biswas, Chinmoy Maji, Samar Sarkar, Tapan K Mandal, Debasish Majumder, Animesh K Chakraborty

Toxicology International 2011 18(2):137-139

Thirty milch cows having arsenic concentration in hair varying from 3 to 4 mg/kg from Dakhin Panchpota village of Nadia district, West Bengal, were divided into three equal groups where high amount of arsenic is reported to be present in soil and ground water. Groups II and III received, respectively, sodium thiosulfate 20 and 40 g to each animal for 30 days as a pilot study, whereas group I served as untreated control. Arsenic content of milk, feces, hair, and urine was estimated before and after administration of sodium thiosulfate orally at two dose level once daily for 1 month. Paddy straw, mustard oil cake, and water fed by animals were also assayed. Sodium thiosulfate significantly decreased arsenic load in milk, urine, and hair after 1 month. In milk, arsenic concentration was decreased significantly which may be beneficial for animal and human beings.

Ameliorative potential of quercetin against paracetamol-induced oxidative stress in mice blood

Sujata Singh — Fri,26 Aug 2011

Sujata Singh, Shanker K Singh, Mritunjay Kumar, Kalpana Chandra, Rashmi Singh

Toxicology International 2011 18(2):140-145

The aim of the present study was to evaluate the ameliorative potential of quercetin (QC) against paracetamol (PCM)-induced oxidative stress and biochemical alterations in mice blood. A total of 36 mice were randomly allocated into six groups, six mice in each. Group I served as healthy controls, while groups II and III were administered with N-acetylcysteine (NAC) and QC alone respectively. Group IV was administered with PCM alone. Groups V and VI were administered with PCM on day 0 followed by NAC and QC, respectively, for 6 consecutive days. On day 7 th blood samples were obtained and subjected for the assays of oxidative stress and serum biochemical panels. Erythrocytic lipid peroxides contents of alone PCM-intoxicated mice were significantly higher, while reduced glutathione contents were found to be significantly lower in comparison with the healthy controls. The activities of antioxidant enzymes were also found to be singnificantly lower in these mice. Additionally, significantly increased activities of serum aspartate transaminase, alanine transaminase and alkaline phosphatase, as well as levels of bilirubin, urea and creatinine were revealed by these mice. Postadministration with QC remarkably alleviated the over production of MDA and improved GSH levels in PCM-intoxicated mice blood. In addition, antioxidant enzymes; glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase activities were also improved significantly in these mice. QC had also considerably ameliorated the altered biochemical parameters toward normalcy. Thus, it can be concluded that QC may constitute a remedy against PCM-induced oxidative stress and reno-hepatic injuries.

A 4-week repeated dose oral toxicity and cytotoxicity study of gumiganghwaltang in Crl:CD (SD) rats

Mee-Young Lee — Fri,26 Aug 2011

Mee-Young Lee, In-Sik Shin, Chang-Seob Seo, Jung-Hoon Kim, Heykyung Ha, Jung-Im Huh, Hyeun-Kyoo Shin

Toxicology International 2011 18(2):146-154

Gumiganghwaltang (GGT) is a traditional oriental herbal prescription commonly used to treat colds and inflammatory diseases in Korea. This study reports the first evaluation of the oral toxicity and cytotoxicity effects of repeat doses of GGT. GGT was orally administered daily at doses of 0, 500, 1000, and 2000 mg/kg for 4 weeks. Analysis of body weight gain, mortality, clinical observations, urinalysis, blood biochemistry, hematology, organ weight, and histopathological data revealed no significant differences between the V.CONTROL and GGT-treated groups. In addition, we investigated the cytotoxicity of GGT against LNCaP, RBL-1, and BEAS-2B cell lines, and splenocytes. Based on the results, we conclude that GGT orally administered to rats is safe with no drug-related toxicity, even at the highest dose, in 4-week repeated dose studies. Thus, this concentration is considered the non-observable effect dose in rats.

Cytogenetic evaluation of the physiological saline extract of a newly developed dental material ''ORMO-48''

PV Mohanan — Fri,26 Aug 2011

PV Mohanan, Lizzy Mol

Toxicology International 2011 18(2):155-159

The ORMO-48 is a new indigenous material for dental applications, developed by the Dental Products Laboratory of our Institute. The aim of the present study was to evaluate the genotoxic effect of an indigenously developed dental material in Swiss albino mice. The genotoxic effect was evaluated by micronucleus and chromosomal aberration tests. Two grams of dental material was extracted in 10.0 ml of physiological saline at 70 o C for 24 h. The extract was cooled to room temperature and was used for the experiment. The experimental designed had three groups each (six mice in each group) for micronucleus and chromosomal aberration tests. The first, second, and third groups were given a single exposure of physiological saline alone (control), dental material's extract (test), and cyclophosphamide (positive control) respectively for micronucleus and chromosomal aberration tests. The result of the study indicated that, the percentage of micronucleated PCE (polychromatic erythrocytes) and NCE (normochromatic erythrocytes) induced by the dental material (extract) treated group was well comparable with control group, whereas the positive control induced significantly high (P < 0.001) micronucleated PCE when compared to control. The PCE and NCE ratio of the dental material extract treated group was similar to that of control group. The chromosomal anomalies such as chromatid/chromosomal breaks, centric rings, exchanges, dicentric, and acentric fragments were evaluated. The result showed that the anomalies of the dental material extract treated group were similar to control group, however, significant anomalies were observed in the cyclophosphamide treated group. Hence, the present study concluded that the indigenously developed biocompatible dental material, ORMO-48 is non genotoxic at our laboratory conditions.

Experimental hepatotoxicity produced by Ethinyl estradiol

Govind Pandey — Fri,26 Aug 2011

Govind Pandey, SP Pandey, Madhuri Sharma

Toxicology International 2011 18(2):160-162

Ethinyl oestradiol (EO) is the most commonly used as a component of oral contraceptive and hormonal replacement therapy (HRT) in women. However, its excessive and prolonged use may cause cytotoxicity, including cancer of many organs. Hence, the present study was performed to produce the experimental hepatotoxicity in female albino rats. EO was administered to different groups of rats, respectively @ 250, 500 and 750 μg/kg body weight, orally, weekly for 16 and 20 weeks. One group of rats was administered with saline alone to serve as control. The rats were sacrificed after their respective experimental periods, and the livers were collected and preserved in 10% buffered formalin. Later on, the histopathological study of liver tissues was done. On the 17 th week, the hepatic tissues showed severe congestion, focal areas of hemorrhage, extreme vacuolation of cytoplasm, distended sinusoids with dilated central veins. Degeneration and necrosis of hepatocytes as evidenced by increased cytoplasmic granularity, and dissolution of nuclear materials were seen. On the 21 st weeks, these changes were extremely severe and quite conspicuous. Distinct fibrosis was also noticed. EO caused hepatotoxicity, the extent and severity of which were dose and time dependent, indicating that this drug at higher dose after prolonged duration (500 or 750 μg/kg, orally, weekly for 20 weeks) may cause the standard experimental hepatotoxicity in rats.

Metal analysis in Citrus Sinensis fruit peel and Psidium Guajava leaf

Anju Dhiman — Fri,26 Aug 2011

Anju Dhiman, Arun Nanda, Sayeed Ahmad

Toxicology International 2011 18(2):163-167

The determination of metal traces is very important because they are involved in biological cycles and indicate high toxicity. The objective of the present study is to measure the levels of heavy metals and mineral ions in medicinally important plant species, Citrus sinensis and Psidium guajava. This study investigates the accumulation of Copper (Cu), Zinc ( Zn), Cadmium (Cd), Aluminum (Al), Mercury (Hg), Arsenic (As), Selenium (Se) and inorganic minerals like Calcium (Ca) and Magnesium (Mg) in C. sinensis (sweet orange) fruit peel and P. guajava (guava) leaf, to measure the levels of heavy metal contamination. Dried powdered samples of the plants were digested using wet digestion method and elemental determination was done by atomic absorption spectrophotometer. Results are expressed as mean ΁ standard deviation and analysed by student's 't' test. Values are considered significant at P < 0.05. The results were compared with suitable safety standards and the levels of Cu, Zn, Cd, Mg and Ca in C. sinensis fruit peel and P. guajava leaves were within the acceptable limits for human consumption. The order of concentration of elements in both the samples showed the following trend: Mg > Ca > Al > Zn > Cu > Cd > Hg = As = Se. The content of Hg, As and Se in C. sinensis fruit peel and P. guajava leaves was significantly low and below detection limit. The content of toxic metals in tested plant samples was found to be low when compared with the limits prescribed by various authorities (World Health Organization, WHO; International Centre for Materials Research, ICMR; American Public Health Association, APHA). The content of Hg, As and Se in C. sinensis fruit peel and P. guajava leaves was not detectable and met the appropriate safety standards. In conclusion, the tested plant parts taken in the present study were found to be safe.

Association of circulating resistin with metabolic risk factors in Indian females having metabolic syndrome

V Gupta — Fri,26 Aug 2011

V Gupta, AK Singh, Vani Gupta, S Kumar, N Srivastava, T Jafar, AB Pant

Toxicology International 2011 18(2):168-172

Role of resistin in insulin sensitivity and metabolic syndrome (MetS) is controversial till date. Increased serum resistin levels are associated with MetS and insulin resistance. The aim of this study was to investigate the relationship between serum resistin levels with markers of the MetS in females. In a cross-sectional study, a total of 170 healthy female subjects were selected for the study. Out of which 71 (age 31.59 ± 4.88 years) were with MetS and 99 (age 31.75 ± 6.34 years) were without MetS. Different parameters of MetS and serum resistin level were measured according to the standard protocols as given in NCEP ATP III 2001 guideline. Serum resistin levels were significantly higher in subjects with MetS when compared with subjects without MetS [13.54 ± 4.14 ng/ml (n = 71) vs. 7.42 ± 2.31 ng/ml (n = 99); P ≤ 0.001]. Resistin levels were positively associated with waist circumference, systolic and diastolic blood pressure, plasma glucose, waist/hip ratio, serum triglycerides, serum cholesterol, serum VLDL, plasma insulin, and insulin resistance, while it was negatively associated with high-density lipoprotein. This study demonstrates a positive correlation between resistin and factors of MetS except high-density lipoprotein which was found to be negatively correlated in Indian female subjects.

Metal concentration in soil

Viroj Wiwanitkit — Fri,26 Aug 2011

Viroj Wiwanitkit

Toxicology International 2011 18(2):173-173

Diagnostic dilemma in a child with tuberculous meningitis on haloperidol therapy

Syed Ahmed Zaki — Fri,26 Aug 2011

Syed Ahmed Zaki, Vijay Lad, Preeti Shanbag

Toxicology International 2011 18(2):173-174