Endosulfan induces reproductive & genotoxic effect in male and female Swiss albino mice.

BACKGROUND: Toxicity by pesticide has become a global health issue and leaves a harmful impact on human health via various ways. The people exposed to pesticides in the rural population get affected by the harmful effects of it as they enter the human body system through skin, inhalation, oral administration, food chain and many more ways. The present work is designed to study the toxic effect of endosulfan in male (n=30) and female (n=30) Swiss albino mice. Endosulfan was administered by oral gavage (oral administration) method, at the dose of 3.5 mg/Kg body weight daily for period of 3 weeks, 5 weeks and 7 weeks. After the completion of the treatment, the mice were sacrificed and their ovary and testis tissues were dissected out to check the degeneration. The blood was collected for karyotyping, biochemical and hormonal analysis of pesticide induced genotoxicity. After 7 weeks of administration with Endosulfan, various abnormalities were observed in male and female mice. RESULTS: Treatment with endosulfan at the dose of 3.5 mg/Kg body weight caused a higher degree of degeneration in the reproductive organ of Swiss albino mice . Treatment by this pesticide generated degeneration in long duration of dosage for 3,5 and 7 weeks. Ovaries of endosulfan administered groups showed degenerated germinal epithelium, Graffian follicles and corpus luteum. In testis of endosulfan treated mice, microscopic examination showed that there is significant damage and reduction in the tissue of seminiferous tubules and primordial germ cells. High degree of degeneration caused the disarrangement and deformation of spermatogonia with the decrease in the number of Sertoli cells. Biochemical and hormonal properties was also affected by endosulfan treatment. There was significant 5 folds decrease in the testosterone value of endosulfan in 7 weeks treated mice in comparison to control (p < 0.0001) and similarly there was significant elevation in the estrogen levels found in 7th week endosulfan treated mice. It also influenced the level of free radicals as there was significant decrease (p < 0.0001) in the value in catalase levels in 7 weeks endosulfan treated male and female mice, while significant (p < 0.0001) increase in the values of lipid peroxidation levels as 8 folds and 10 folds in 7 weeks endosulfan treated male and female Swiss albino mice respectively. This study hence speculates that the endosulfan exposed population are at the risk of reproductive health hazards. CONCLUSIONS: The present study thus concludes that, endosulfan after 7 weeks of exposure caused significant reproductive damage to both male and female Swiss albino mice groups. Moreover, the karyotyping study also correlated the genotoxic damage in the mice.

Severe Disease Burden and the Mitigation Strategy in the Arsenic-Exposed Population of Kaliprasad Village in Bhagalpur District of Bihar, India.

The present study was carried out in the village Kaliprasad of Bhagalpur district of Bihar to know the arsenic exposure effect in the exposed population. A total of n = 102 households were studied, and their water and biological samples such as urine and hair were collected and analyzed in a graphite furnace atomic absorption spectrophotometer (GF-AAS). The assessment of arsenic-exposed village population reveals that the villagers were suffering from serious health-related problems such as skin manifestations (hyperkeratosis and melanosis in their palm and soles), breathlessness, general body weakness, mental disorders, diabetes, hypertension (raised blood pressure), hormonal imbalance, neurological disorders, and few cancer cases. About 77% of household hand pump water had arsenic level more than the WHO recommended level of 10 µg/L, with highest level of 523 µg/L. Moreover, in 60% individual's urine samples, arsenic concentration was very high with maximum 374 µg/L while in hair 64% individuals had arsenic concentration above the permissible limit with maximum arsenic concentration of 11,398 µg/kg. The hazard quotient (HQ) was also calculated to know the arsenic risk percentage in children as 87.11%, in females as 83.15%, and in males as 82.27% by groundwater. This has surpassed the threshold value of 1 × 10 - 6 for carcinogenic risk (CR) in children, female, and male population group in the village. Hence, the exposed population of Kaliprasad village are at very high risk of the disease burden.

Arsenic causing gallbladder cancer disease in Bihar.

In recent times Gallbladder cancer (GBC) incidences increased many folds in India and are being reported from arsenic hotspots identified in Bihar. The study aims to establish association between arsenic exposure and gallbladder carcinogenesis. In the present study, n = 200 were control volunteers and n = 152 confirmed gallbladder cancer cases. The studied GBC patient's biological samples-gallbladder tissue, gallbladder stone, bile, blood and hair samples were collected for arsenic estimation. Moreover, n = 512 gallbladder cancer patients blood samples were also evaluated for the presence of arsenic to understand exposure level in the population. A significantly high arsenic concentration (p < 0.05) was detected in the blood samples with maximum concentration 389 µg/L in GBC cases in comparison to control. Similarly, in the gallbladder cancer patients, there was significantly high arsenic concentration observed in gallbladder tissue with highest concentration of 2166 µg/kg, in gallbladder stones 635 µg/kg, in bile samples 483 µg/L and in hair samples 6980 µg/kg respectively. Moreover, the n = 512 gallbladder cancer patient's blood samples study revealed very significant arsenic concentration in the population of Bihar with maximum arsenic concentration as 746 µg/L. The raised arsenic concentration in the gallbladder cancer patients' biological samples-gallbladder tissue, gallbladder stone, bile, blood, and hair samples was significantly very high in the arsenic exposed area. The study denotes that the gallbladder disease burden is very high in the arsenic exposed area of Bihar. The findings do provide a strong link between arsenic contamination and increased gallbladder carcinogenesis.

Protective efficacy of Coriandrum sativum seeds against arsenic induced toxicity in Swiss albino mice.

Arsenic poisoning in ground water is one of the most sensitive environmental pollutant causing serious pollution all over the world. Chronic arsenic exposure through drinking water to humans leads to major public health related issues. There have been very meagre studies which reported that, the plant constituents proved to exhibit protective effect from arsenicosis. Therefore, the present study aims to evaluate the protective efficacy of Coriandrum sativum seeds extract against sodium arsenite induced toxicity in Swiss albino mice. In the present study twenty-four male healthy Swiss albino mice (30 ± 5 g) were divided into four groups (n = 6), where the control group received normal diet and water; group II and group III treated with sodium arsenite (2 mg per kg body weight per day) for 2 and 4 weeks respectively. The group IV mice were administered with C.sativum seeds extract at the dose of 150 mg per kg body weight per day for 4 weeks upon sodium arsenite pretreated (2 mg/kg body weight for 4 weeks per day) mice. After the complete dose duration, all the treatment group animals were sacrificed same day for haematological, biochemical and histopathological study. In the arsenic treated mice, there were significant (p < 0.0001) changes in the serum levels of ALT, AST, ALP, urea, uric acid and creatinine as well as in the haematological parameters. In contrast, after the administration with C.sativum seeds extract upon arsenic pretreated mice, there was significant (p < 0.0001) improvement observed in the hepatic and renal biomarker parameters as well as haematological variables. In the arsenic intoxicated mice,  after administration with C.sativum seeds extract there was significant (p < 0.0001) reduction in the arsenic concentration in blood, liver and kidney tissues as well as in the serum LPO levels. Furthermore, the histopathological study showed that, C.sativum seeds extract administrated group of mice significantly restored the liver and kidney at cellular level against arsenic induced toxicity. The entire study concludes that C.sativum seeds extract possesses the ameliorative effect against arsenic induced liver and kidney intoxication.

Assessment of disease burden in the arsenic exposed population of Chapar village of Samastipur district, Bihar, India, and related mitigation initiative.

Fast growing arsenic menace is causing serious health hazards in Bihar, India, with an estimated 10 million people at risk. The exposed population is often unaware of the problem, which only amplifies the burden of arsenic health effects. In the present study, we have assessed the current situation of arsenic exposure in Chapar village of Samastipur district, Bihar. The health of the inhabitants was assessed and correlated with (1) arsenic concentrations in the groundwater of individual wells and (2) arsenic concentration found in their hair and urine. Altogether, 113 inhabitants were assessed, and 113 hair, urine and groundwater samples were collected. The health study reveals that the exposure to arsenic has caused serious health hazard amongst the exposed population with pronounced skin manifestations, loss of appetite, anaemia, constipation, diarrhoea, general body weakness, raised blood pressure, breathlessness, diabetes, mental disabilities, diabetes, lumps in the body and few cancer incidences. It was found that 52% of the total collected groundwater samples had arsenic levels higher than the WHO limit of 10 µg/l (with a maximum arsenic concentration of 1212 µg/l) and the reduced arsenite was the predominant form in samples tested for speciation (N = 19). In the case of hair samples, 29% of the samples had arsenic concentrations higher than the permissible limit of 0.2 mg/kg, with a maximum arsenic concentration of 46 µg/l, while in 20% exposed population, there was significant arsenic contamination in urine samples > 50 µg/l. In Chapar village, the probability of carcinogenic-related risk in the exposed population consuming arsenic contaminated water is 100% for children, 99.1% for females and 97.3% for male subjects. The assessment report shared to the government enabled the village population to receive two arsenic filter units. These units are currently operational and catering 250 households providing arsenic-free water through piped water scheme. This study therefore identified a significant solution for this arsenic-exposed population.

Assessment of arsenic exposure in the population of Sabalpur village of Saran District of Bihar with mitigation approach.

Arsenic poisoning through groundwater is the world's greatest normal groundwater catastrophe which got an immense effect on worldwide general wellbeing. India is confronting the outcomes of arsenic poisoning in the zone of Ganga Brahmaputra alluvial plains. In Bihar, out of 38 districts, 18 districts are exceptionally influenced with groundwater arsenic defilement. In the present study, we have assessed the current situation of arsenic exposure in Sabalpur village of Saran district of Bihar after reporting of breast, renal, skin and thyroid cancer cases from this village along with typical symptoms of arsenicosis. Such cancer patients were identified at our institute and were taken for the study. The present investigation deals with the quantification of arsenic in groundwater, hair and nail samples of subjects as well as the survey of entire village to know the overall health status of the village people. A total of n=128 household handpump water samples as well as n=128 human hair and nail samples were collected from over n=520 households. Using the graphite furnace atomic absorption spectrophotometer (GF-AAS), all the samples were analysed. The investigation resulted that the 61% of the analysed samples particularly the groundwater had the arsenic levels more than the permissible limit of WHO (> 10 µg/L) with 244.20 µg/L as the highest arsenic contamination in one of the handpump water sample. The exposure effect of hair sample was worst as 88% of all the collected samples were having high arsenic levels more than the permissible limit (> 0.2 mg/Kg). In case of nail samples, 92% of the samples were having high arsenic concentration more than the permissible limit (> 0.5 mg/Kg). The health survey study revealed high magnitude of disease burden in the exposed population with symptoms such as asthma, anaemia, hepatomegaly, diabetes, cardiac problem, skin fungal infections, breathlessness and mental disability. Few cancer cases of renal, skin, breast and cervix were also found among the exposed population of this village. The percentage of cancer cases in this village was 0.94% that was low, but it would be an aggravated situation in the near future if people will continue drinking arsenic-contaminated water. Therefore, a mitigation intervention was carried out in March 2020 by installing an arsenic filter plant. The health situation in the village in the present scenario is hope to improve in the coming years. However, motivation and awareness among the village population are still required.

Analysis of mitochondrial DNA copy number variation in blood and tissue samples of metastatic breast cancer patients (A pilot study).

Changes in mitochondrial DNA (mt-DNA) copy number in blood/tissue have been linked to increased risk of several cancers; however, studies on their association in breast cancer is still lacking. In this pilot study, we investigated mt-DNA copy number variation in peripheral blood and tissue samples from metastatic breast cancer patients and compared their differences. For the study, peripheral blood samples from non-cancer individuals (control) and breast cancer patients, along with resected tissues from adjacent and tumor sites from same breast cancer patients were collected. Total genomic DNA was isolated and changes in mt-DNA copy number were measured by relative quantification using SYBR green based quantitative real time PCR method. Our results indicated a significant reduction in mt-DNA copy number in blood samples of breast cancer patients compared to control. However, a significantly higher mt-DNA copy number was observed in tumor tissue when compared with paired non tumor tissue. There was no significant difference in mt-DNA copy number between blood and adjacent tumor tissue samples of the breast cancer patients. Overall, our study reports for the first time a comparison of mt-DNA copy number in blood and paired tissue together and suggested that mt-DNA copy number is differentially regulated in blood and tumor tissues in breast cancer.

Arsenic exposure in Indo Gangetic plains of Bihar causing increased cancer risk.

Reportedly, 300 million people worldwide are affected by the consumption of arsenic contaminated groundwater. India prominently figures amongst them and the state of Bihar has shown an upsurge in cases affected by arsenic poisoning. Escalated arsenic content in blood, leaves 1 in every 100 human being highly vulnerable to being affected by the disease. Uncontrolled intake may lead to skin, kidney, liver, bladder, or lung related cancer but even indirect forms of cancer are showing up on a regular basis with abnormal arsenic levels as the probable cause. But despite the apparent relation, the etiology has not been understood clearly. Blood samples of 2000 confirmed cancer patients were collected from pathology department of our institute. For cross-sectional design, 200 blood samples of subjects free from cancer from arsenic free pockets of Patna urban agglomeration, were collected. Blood arsenic levels in carcinoma patients as compared to sarcomas, lymphomas and leukemia were found to be higher. The geospatial map correlates the blood arsenic with cancer types and the demographic area of Gangetic plains. Most of the cancer patients with high blood arsenic concentration were from the districts near the river Ganges. The raised blood arsenic concentration in the 2000 cancer patients strongly correlates the relationship of arsenic with cancer especially the carcinoma type which is more vulnerable. The average arsenic concentration in blood of the cancer patients in the Gangetic plains denotes the significant role of arsenic which is present in endemic proportions. Thus, the study significantly correlates and advocates a strong relation of the deleterious element with the disease. It also underlines the need to address the problem by deciphering the root cause of the elevated cancer incidences in the Gangetic basin of Bihar and its association with arsenic poisoning.

Wheat is an emerging exposure route for arsenic in Bihar, India.

In arsenic (As) endemic areas of south-east Asia, where a subsistence rice-based diet is prevalent, As exposure from food is mainly focused on rice intake. However, consumption of wheat is substantial and increasing. We present a probabilistic assessment of increased cancer risk from wheat-based food intake in a study population of rural Bihar, India where As exposure is endemic. Total As in wheat grains (43.64 ±â€¯48.19 µg/kg, n = 72) collected from 77 households across 19 villages was found to be lower than reported As in wheat grains from other south-east Asian countries but higher than a previous study from Bihar. This is the first study where As concentration in wheat flour was used for risk estimation, bearing in mind that it was the flour obtained after indigenous household processing of the grains that was used for making the home-made bread (chapati) which contributed 95% of wheat intake for the studied population. Interestingly, while 78% of the surveyed participants (n = 154) consumed rice every day, chapati was consumed every day by 99.5% of the participants. In contrast to previous studies, where As concentration in wheat grains was found to be lower than the flour due to the removal of the bran on grinding, we did not find any appreciable lowering of arsenic in the wheat flour (49.80 ±â€¯74.08 µg/kg, n = 58), most likely due to external contamination during processing and grinding. Estimated gender adjusted excess lifetime cancer risk of 1.23 × 10-4 for the studied rural population of Bihar indicated risk higher than the 10-4-10-6 range, typically used by the USEPA as a threshold to guide regulatory values. Hence, our findings suggest As exposure from wheat-based food intake to be of concern not only in As endemic areas of rural Bihar but also in non-endemic areas with similar wheat-based diet due to public distribution of the wheat across India.

Comparative Quantification Study of Arsenic in the Groundwater and Biological Samples of Simri Village of Buxar District, Bihar, India.

BACKGROUND: In the entire world, about 200 million populations are exposed to arsenic poisoning in groundwater. In Bihar, India about 50 million people are drinking arsenic contaminated water. This has caused various health related problems in the population like skin diseases, anemia, bronchitis, gastrointestinal problems, hormonal imbalance and cancer. MATERIALS AND METHODS: In the present study, a total of 323 water samples were analyzed for the arsenic levels from the entire Simri village of Buxar district of Bihar and a total of 170 blood samples from the same household's subjects were collected for blood arsenic estimation through Graphite Furnace Atomic Absorption Spectrophotometer (Pinnacle 900T, Perkin Elmer, Singapore). Apart from this the correlation coefficient study between blood arsenic levels, age of the subjects, groundwater arsenic levels and depth of the handpumps were carried out. STATISTICAL ANALYSIS: Data were analyzed with statistical software (GraphPad Prism 5) and while scattered graphs were plotted through statistical software SPSS- 16.0. RESULTS AND CONCLUSION: The maximum arsenic concentration in the groundwater sample found during the study was 1929µg/L and in blood sample was 664.7µg/L. The study denotes high arsenic concentration in the drinking water of the village Simri with the highest concentration ever reported in this part of India. Furthermore, the blood samples have also been observed with high arsenic concentration in the village population which is also the highest reporting ever done in this area. The ill health of the village population also correlates our study.

Chronic Arsenic Exposure and Risk of Post Kala-azar Dermal Leishmaniasis Development in India: A Retrospective Cohort Study.

BACKGROUND: Visceral leishmaniasis (VL), with the squeal of Post-kala-azar dermal leishmaniasis (PKDL), is a global threat for health. Studies have shown sodium stibogluconate (SSG) resistance in VL patients with chronic arsenic exposure. Here, we assessed the association between arsenic exposure and risk of developing PKDL in treated VL patients. METHODS: In this retrospective study, PKDL patients (n = 139), earlier treated with SSG or any other drug during VL, were selected from the study cohort. Trained physicians, unaware of arsenic exposure, interviewed them and collected relevant data in a questionnaire format. All probable water sources were identified around the patient's house and water was collected for evaluation of arsenic concentration. A GIS-based village-level digital database of PKDL cases and arsenic concentration in groundwater was developed and individual point location of PKDL cases were overlaid on an integrated GIS map. We used multivariate logistic regression analysis to assess odds ratios (ORs) for association between arsenic exposure and PKDL development. RESULTS: Out of the 429 water samples tested, 403 had arsenic content of over 10 µg/L, with highest level of 432 µg/L among the seven study villages. Multivariate adjusted ORs for risk of PKDL development in comparison of arsenic concentrations of 10.1-200 µg/L and 200.1-432.0 µg/L were 1.85 (1.13-3.03) and 2.31 (1.39-3.8) respectively. Interestingly, similar results were found for daily dose of arsenic and total arsenic concentration in urine sample of the individual. The multivariate-adjusted OR for comparison of high baseline arsenic exposure to low baseline arsenic exposure of the individuals in the study cohort was 1.66 (95% CI 1.02-2.7; p = 0.04). CONCLUSION: Our findings indicate the need to consider environmental factors, like long time arsenic exposure, as an additional influence on treated VL patients towards risk of PKDL development in Bihar.

Ground Water Arsenic Contamination: A Local Survey in India.

BACKGROUND: In the present times, arsenic poisoning contamination in the ground water has caused lots of health-related problems in the village population residing in middle Gangetic plain. In Bihar, about 16 districts have been reported to be affected with arsenic poisoning. For the ground water and health assessment, Simri village of Buxar district was undertaken which is a flood plain region of river Ganga. METHODS: In this study, 322 water samples were collected for arsenic estimation, and their results were analyzed. Furthermore, the correlation between arsenic contamination in ground water with depth and its distance from river Ganga were analyzed. Results are presented as mean ± standard deviation and total variation present in a set of data was analyzed through one-way analysis of variance. The difference among mean values has been analyzed by applying Dunnett's test. The criterion for statistical significance was set at P < 0.05. RESULTS: This study shows novel findings ever done in this area. Halwa Patti and Doodhi Patti strips were the most affected strips with high-arsenic concentration in hand pumps. Furthermore, a correlation between the arsenic concentration with the depth of the hand pumps and the distance from the river Ganga was also a significant study. CONCLUSIONS: The present study concludes that in Simri village there is high contamination of arsenic in ground water in all the strips. Such a huge population is at very high risk leading the village on the verge of causing health hazards among them. Therefore, an immediate strategy is required to combat the present problem.