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  1. Rahman F, Ismail A, Omar H, Hussin MZ
    Toxicol Rep, 2017;4:502-506.
    PMID: 28959680 DOI: 10.1016/j.toxrep.2017.09.003
    The Milky stork is listed as an endangered species endemic to the Southeast Asia region. In Malaysia, the population is currently being reintroduced back into the wild. However, the increase of anthropogenic activity throughout the coastal area might expose the population to hazardous chemicals such as heavy metals. This study highlights the contamination of cadmium (Cd) and lead (Pb) in the Milky stork's diet. Additionally, this is the first time an integrated exposure model being used to assess heavy metal exposure risk to the population. Lead level (5.5-7.98 mg kg-1) in particular was relatively high compared to Cd (0.08-0.33 mg kg-1). This was probably related to the different niches occupied by the species in the aquatic environment. The results further show that the predicted exposure doses (through intake of both food and water) for all metals are much lower than the Tolerable Daily Intake (TDI) values. The total exposure dose for Cd was 0.11 mg kg-1 d-1 with TDI value of 0.54 mg kg-1 d-1 while Pb total exposure dose was 0.31 mg kg-1 d-1 with TDI value of 0.64 mg kg-1 d-1. Several possible factors that could lead to the observed pattern were discussed. In conclusion, there is an urgent need to improve the current habitat quality to protect the endangered species. The authors also emphasized on the protection of remaining Milky stork's habitats i.e. mudflats and mangroves and the creation of buffer zone to mitigate the negative impacts that may arise from pollution activity.
  2. Jahan S, Yusoff IB, Alias YB, Bakar AFBA
    Toxicol Rep, 2017;4:211-220.
    PMID: 28959641 DOI: 10.1016/j.toxrep.2017.04.001
    Presently, engineered nanomaterials (ENMs) are used in a wide variety of commercial applications, resulting in an uncontrolled introduction into the aquatic environment. The purpose of this review is to summarize the pathways and factors that controlling the transport and toxicity of five extensively used ENMs. These toxicological pathways are of great importance and need to be addressed for sustainable implications of ENMs without environmental liabilities. Here we discuss five potentially utilized ENMs with their possible toxicological risk factors to aquatic plants, vertebrates model and microbes. Moreover, the key effect of ENMs surface transformations by significant reaction with environmental objects such as dissolved natural organic matter (DOM) and the effect of ENMs surface coating and surface charge will also be debated. The transformations of ENMs are subsequently facing a major ecological transition that is expected to create a substantial toxicological effect towards the ecosystem. These transformations largely involve chemical and physical processes, which depend on the properties of both ENMs and the receiving medium. In this review article, the critical issues that controlling the transport and toxicity of ENMs are reviewed by exploiting the latest reports and future directions and targets are keenly discussed to minimize the pessimistic effects of ENMs.
  3. Sarkar T, Alam MM, Parvin N, Fardous Z, Chowdhury AZ, Hossain S, et al.
    Toxicol Rep, 2016;3:346-350.
    PMID: 28959555 DOI: 10.1016/j.toxrep.2016.03.003
    This study is aimed to assess the heavy metals contamination and health risk in Shrimp (Macrobrachium rosenbergii and Penaeus monodon) collected from Khulna-Satkhira region in Bangladesh. The results showed that the Pb concentrations (0.52-1.16 mg/kg) in all shrimp samples of farms were higher than the recommended limit. The Cd levels (0.05-0.13 mg/kg) in all samples and Cr levels in all farms except tissue content at Satkhira farm were higher than the permissible limits. The individual concentration of Pb, Cd, and Cr between shrimp tissue and shell in all rivers and farms were not statistically significant (P > 0.05). Target hazard quotient (THQ) and hazard index (HI) were estimated to assess the non-carcinogenic health risks. Shrimp samples from all locations under the current study were found to be safe for consumption, the possibility of health risk associated with non-carcinogenic effect is very low for continuous consumption for 30 years.
  4. Parasuraman S, Raveendran R, Rajesh NG, Nandhakumar S
    Toxicol Rep, 2014;1:596-611.
    PMID: 28962273 DOI: 10.1016/j.toxrep.2014.08.006
    OBJECTIVE: To investigate the toxicological effects of cleistanthin A and cleistanthin B using sub-chronic toxicity testing in rodents.

    METHOD: Cleistanthins A and B were isolated from the leaves of Cleistanthus collinus. Both the compounds were administered orally for 90 days at the concentration of 12.5, 25 and 50 mg/kg, and the effects on blood pressure, biochemical parameters and histology were assessed. The dose for sub-chronic toxicology was determined by fixed dose method according to OECD guidelines.

    RESULT: Sub-chronic toxicity study of cleistanthins A and B spanning over 90 days at the dose levels of 12.5, 25 and 50 mg/kg (once daily, per oral) revealed a significant dose dependant toxic effect in lungs. The compounds did not have any effect on the growth of the rats. The food and water intake of the animals were also not affected by both cleistanthins A and B. Both the compounds did not have any significant effect on liver and renal markers. The histopathological analysis of both cleistanthins A and B showed dose dependent morphological changes in the brain, heart, lung, liver and kidney. When compared to cleistanthin A, cleistanthin B had more toxic effect in Wistar rats. Both the compounds have produced a dose dependent increase of corpora amylacea in brain and induced acute tubular necrosis in kidneys. In addition, cleistanthin B caused spotty necrosis of liver in higher doses.

    CONCLUSION: The present study concludes that both cleistanthin A and cleistanthin B exert severe toxic effects on lungs, brain, liver, heart and kidneys. They do not cause any significant pathological change in the reproductive system; neither do they induce neurodegenerative changes in brain. When compared to cleistanthin A, cleistanthin B is more toxic in rats.

  5. Koh KH, Tan CH, Hii LW, Lee J, Ngu LL, Chai AJ, et al.
    Toxicol Rep, 2014;1:490-495.
    PMID: 28962262 DOI: 10.1016/j.toxrep.2014.06.010
    Paraquat poisoning resulted in multiorgan failure and is associated with high mortality. We audited 83 historical cases of paraquat poisoning in past 2 years treated with conventional decontamination and supportive treatment, followed by enrolling 85 patients over a 2 year period into additional immunosuppression with intravenous (i.v.) methylprednisolone and i.v. cyclophosphamide. Our results showed that age, poor renal function and leucocytosis are the main predictors of fatal outcome. Immunosuppression regime rendered higher survival (6 out of 17 patients (35.3%)) versus historical control (1 out of 18 patients (5.6%)) (p = 0.041) in the cohort with admission eGFR < 50 ml/min/1.73 m(2) and WBC count > 11,000/μL. In contrast, there was no difference in survival with immunosuppression regime (38 out of 64 patients (59.4%)) compared to historical control (30 out of 52 patients (57.7%)) (p = 0.885) in those with eGFR > 50 ml/min/1.73 m(2) or WBC < 11,000/μL at presentation. Multivariable logistic regression showed survival probability = exp(logit)/(1 + exp(logit)), in which logit = 13.962 - (0.233 × ln(age (year))) - (1.344 × ln(creatinine (μmol/L))) - (1.602 × ln(rise in creatinine (μmol/day))) - (0.614 × ln(WBC (,000/μL))) + (2.021 × immunosuppression) and immunosuppression = 1 if given and 0 if not. Immunosuppression therapy yielded odds ratio of 0.132 (95% confidential interval: 0.029-0.603, p = 0.009). In conclusion, immunosuppression therapy with intravenous methylprednisolone and cyclophosphamide may counteract immune mediated inflammation after paraquat poisoning and improve survival of patients with admission eGFR < 50 ml/min/1.73 m(2) and WBC count > 11,000/μL.
  6. Aboonabi A, Rahmat A, Othman F
    Toxicol Rep, 2014;1:915-922.
    PMID: 28962304 DOI: 10.1016/j.toxrep.2014.10.022
    Oxidative stress attributes a crucial role in chronic complication of diabetes. The aim of this study was to determine the most effective part of pomegranate on oxidative stress markers and antioxidant enzyme activities against streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. Male Sprague-Dawley rats were randomly divided into six groups. Experimental diabetes was induced by a single intraperitoneal injection (i.p), 15 min after the i.p administration of NA. Diabetic rats showed significant increase in plasma glucose level, and the significant decrease in plasma insulin level. The activities of antioxidant enzymes such as total antioxidant status (TAS), superoxide dismutase (SOD), and catalase (CAT) reduced while the levels of biomarkers of oxidative stress such as gamma-glutamyle transferase (GGT), and malondialdehyde (MDA) increased in diabetic control rats as compared to normal control rats. Oral treatment with pomegranate seed-juice for 21 days demonstrated significant protective effects on all the biochemical parameters studied. Besides, biochemical findings were supported by histopathological study. These results revealed that pomegranate has potential protective effect against oxidative stress induced diabetic rats.
  7. Manaharan T, Chakravarthi S, Radhakrishnan AK, Palanisamy UD
    Toxicol Rep, 2014;1:718-725.
    PMID: 28962285 DOI: 10.1016/j.toxrep.2014.09.006
    In this study, the acute and subchronic toxicity effect of the Syzygium aqueum leaf extract (SA) was evaluated. For the acute toxicity study, a single dose of 2000 mg/kg of the SA was given by oral-gavage to male Sprague-Dawley (SD) rats. The rats were observed for mortality and toxicity signs for 14 days. In the subchronic toxicity study the SA was administered orally at doses of 50, 100, and 200 mg/kg per day for 28 days to male SD rats. The animals were sacrificed at the end of the experiment. The parameters measured including food and water intake, body weight, absolute and relative organ weight, blood biochemical tests and histopathology observation. In both the acute and subchronic toxicity studies, SA did not show any visible signs of toxicity. There were also no significant differences between the control and SA treated rats in terms of their food and water intake, body weight, absolute and relative organ weight, biochemical parameters or gross and microscopic appearance of the organs. There were no acute or subchronic toxicity observed and our results indicate that this extract could be devoid of any toxic risk. This is the first in vivo study reported the safety and toxicity of SA.
  8. Mohamed K, Zine K, Fahima K, Abdelfattah E, Sharifudin SM, Duduku K
    Toxicol Rep, 2018;5:480-488.
    PMID: 29854619 DOI: 10.1016/j.toxrep.2018.03.012
    Nickel oxide nanoparticles (NiO NPs) have attracted increasing attention owing to potential capacity to penetrate to several human cell systems and exert a toxic effect. Elsewhere, the use of medicinal plants today is the form of the most widespread medicine worldwide. Utilizing aromatic plants as interesting source of phytochemicals constitute one of the largest scientific concerns. Thus this study was focused to investigate antioxidant and cytoprotective effects of essential oil of a Mediterranean plant P. lentiscus (PLEO) on NiO NPs induced cytotoxicity and oxidative stress in human lung epithelial cells (A549). The obtained results showed that cell viability was reduced by NiO NPs, who's also found to induce oxidative stress in dose-dependent manner indicated by induction of reactive oxygen species and reduction of antioxidant enzymes activities. Our results also demonstrated that PLEO contains high amounts in terpinen-4-ol (11.49%), germacrene D (8.64%), α-pinene (5.97%), sabinene (5.19%), caryophyllene (5.10%) and δ-Cadinene (4.86%). PLEO exhibited a potent antioxidant capacity by cell viability improving, ROS scavenging and enhancing the endogenous antioxidant system against NiO NPs in this model of cells. The present work demonstrated, for the first time, the protective activity of PLEO against cell oxidative damage induced by NiO NPs. It was suggested that this plant essential oil could be use as a cells protector.
  9. Maurya PK, Malik DS, Yadav KK, Kumar A, Kumar S, Kamyab H
    Toxicol Rep, 2019;6:472-481.
    PMID: 31193923 DOI: 10.1016/j.toxrep.2019.05.012
    This paper assesses the potential human health risks posed by five heavy metals (Zn, Pb, Cu, Cd, and Cr) found in seven most consumable fish species (Cirrhinus mrigala, Cirrhinus reba, Catla catla, Lebio rohita, Crossocheilus latius, Clupisoma garua, and Mystus tengara) collected from local markets of Varanasi, Allahabad, Mirzapur, and Kanpur of Uttar Pradesh, India. The Cu concentration was found at Varanasi (4.58 mg/l), Allahabad (2.54 mg/l), and Mirzapur (2.54 mg/l). Pb was recorded 0.54, 0.62, 0.85, and 0.24 mg/l at Kanpur, Allahabad, Mirzapur, and Varanasi, respectively. The Cd concentration was recorded 0.54, 0.68, 0.78, and 0.85 mg/l at Kanpur, Allahabad, Mirzapur, and Varanasi, respectively. The Cr, Cd, and Pb concentrations in the river water were observed over the prescribed safe limits at all sampling sites, while Cu concentration was higher than the standards at all sites except Kanpur. However, Zn was observed under the permissible limits (15 mg/l) at all sampling sites. In case of fish tissues, WHO reported the concentration of Pb, Cd, and Cr higher than the prescribed safe limits. The results determined that the highest heavy metals accumulation was found settled in the liver of all selected fish species. Zn ranked the highest quantity, which was found in fish tissues with the concentration of 32.41 ± 2.55 μg/g in the gill of C. catla and 4.77 ± 0.34 μg/g in the gill C. Reba. The metals followed the magnitude order of Zn > Pb > Cu > Cd > Cr in selected fish tissues.
  10. Athar Abbasi M, Yu SM, Aziz-Ur-Rehman, Siddiqui SZ, Kim SJ, Raza H, et al.
    Toxicol Rep, 2019;6:897-903.
    PMID: 31516842 DOI: 10.1016/j.toxrep.2019.08.016
    In the study presented here, a novel chlorobenzylated bi-heterocyclic hybrid molecule (7) was synthesized and its structural confirmation was carried out by IR, 1H-NMR, 13C-NMR and CHN analysis data. This compound 7 was subjected to biological study with B16F10 mouse melanoma cells. The anti-proliferative results showed that 7 showed no significant toxicity at concentrations ranging of 0-44 μM. The treatment of B16F10 cells with 7 at aforementioned concentration range indicated that migration of cells was significantly lower than that of the control cells in a dose dependent manner. The possible migration inhibitory effect of these melanoma cells was further evaluated through gelatinolytic activity of MMP-2 and MMP-9 secreted from B16F10 cells. It was inferred from our results that 7 was not affecting the expression and activity of these enzymes. Some other zinc-dependent matrix metalloproteinases (MMPs) were involved in the inhibitory progression. Taken together, compound 7 inhibited migrations of B16F10 mouse melanoma cells. Therefore, it may deserve consideration as a potential agent for the treatment of cancer.
  11. Murugesu S, Khatib A, Ahmed QU, Ibrahim Z, Uzir BF, Benchoula K, et al.
    Toxicol Rep, 2019;6:1148-1154.
    PMID: 31993329 DOI: 10.1016/j.toxrep.2019.10.020
    Clinacanthus nutans, an herbal shrub belonging to the Acanthaceae family, is traditionally used as a functional food to treat various ailments in Malaysia and Indonesia. Although the polar fraction of this plant shows non-toxic effect, the toxicity of the non-polar extract is not reported so far. The present study aimed to assess the toxic effect and determine the lethal concentration of this non-polar fraction using zebrafish embryos. The n-hexane fraction was partitioned from the crude extract of C. nutans obtained using 80% methanolic solution. After spawning of the adult male and female zebrafish, the eggs were collected, transferred into a 96-well plate and incubated with the n-hexane fraction at concentrations of 15.63 μg/ml, 31.25 μg/ml, 62.5 μg/ml, 125 μg/ml, 250 μg/ml and 500 μg/ml in 2% DMSO. The survival and sublethal endpoint were assessed, the mortality and hatchability rates were calculated based on microscopic observation, while the heartbeat rate was measured using DanioScope software. The median lethal concentration (LC50) of the C. nutans n-hexane fraction, which was determined using probit analysis, was calculated to be 75.49 μg/mL, which is harmful. Moreover, gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of palmitic acid, phytol, hexadecanoic acid, 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol and stigmasterol in the n-hexane fraction.
  12. Kaur S, Muthuraman A
    Toxicol Rep, 2019;6:505-513.
    PMID: 31211096 DOI: 10.1016/j.toxrep.2019.06.001
    The present study has been investigated the role of gallic acid (GA) in paclitaxel-induced neuropathic pain. The neuropathic pain was developed with paclitaxel (PT: 2 mg/kg, i.p.) administration in mice. GA (20 and 40 mg/kg) and pregabalin (PreG: 5 mg/kg) were administered intravenously for 10 consecutive days. The neuralgic sensations were investigated by assessing various pain tests like acetone drop, pinprick, plantar, tail flick, and tail pinch test. Mice pain behaviors were evaluated on 0, 4th, 8th, 12th and 16th days. The levels of sciatic nerve thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide anion, calcium, myeloperoxidase (MPO), and TNF-α were estimated. Treatment of GA and PreG attenuate PT induced thermal &mechanical hyperalgesia and allodynia symptoms along with the reduction of TBARS, total calcium, TNF-α, superoxide anion, and MPO activity levels; and decreased GSH level. Therefore, it has been concluded that GA has potential neuroprotective actions against PT induced neuropathic pain due to it's anti-oxidant, anti-inflammation and regulation of intracellular calcium ion concentration.
  13. Ahmad NS, Abdullah N, Yasin FM
    Toxicol Rep, 2020;7:693-699.
    PMID: 32528857 DOI: 10.1016/j.toxrep.2020.04.015
    Toxicity effect of reduced graphene oxide (rGO) and titanium dioxide (TiO2) nanomaterials (NMs) on Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria was assessed. For both strains, study demonstrated that the toxicity was time and concentration dependent which led to reduction in growth rate and cell death. Upon NMs exposure, an instantaneous cell death in E. coli culture was observed. This is in contrast with B. subtilis, in which the culture growth remained in the log phase; however their growth rate constant,

    μ
    g

    was reduced by ∼70%. The discrepancy between E. coli and B. subtilis was due to strain-specific response upon contact with NMs. TEM, SEM and EDX analysis revealed direct physical surface-surface interaction, as evidence from the adherence of NMs on the cell surface.
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