Hasil untuk "Toxicology. Poisons"

L. Sánchez-Sánchez, H. López-Muñoz, O. M. Echeverría et al.

Quercetagetin is a flavonoid that has shown antiproliferative effects against different human cancers. We thoroughly analysed the effects of quercetagetin obtained from Tagetes erecta on human triple-negative breast cancer cells (MDA-MB-231) and murine breast cancer cells (JC) to elucidate its underlying antineoplastic mechanisms. Quercetagetin exerted dose-dependent antiproliferative effects on both cell lines (half-maximal inhibitory concentration: 188 and 282 μM, respectively). While it eliminated MDA-MB-231 cells via both apoptosis and autophagy, it predominantly eliminated JC cells via ferroptosis. Our results demonstrate that quercetagetin induces different programmed cell death pathways in a species-specific manner. Notably, quercetagetin did not significantly affect the proliferation of noncancerous lymphocytic cells. These data may facilitate the development of anticancer drugs that induce programmed cell death with fewer side effects.

Adel Ghorbani, Mahmoud Ghazaghi, Farzad Bagherzadeh-Kasmani et al.

This study aimed to investigate the effects of dietary methionine (Met) supplementation on performance, immunity, and meat quality in growing Japanese quail exposed to aflatoxin B1 (AFB1)-contaminated diets. Nine experimental diets were formulated, incorporating three levels of dietary Met (5.0, 6.0, and 7.0 g/kg) and three levels of AFB1 (0.0, 2.5, and 5.0 mg/kg) in a completely randomized design and fed from d 8 post-hatch to d 35 of age. The results revealed that increasing dietary Met levels significantly improved body weight gain (BWG; P < 0.001), feed conversion ratio (FCR; P < 0.001), and feed intake (FI; P < 0.001), while counteracting the negative effects of AFB1 on these performance parameters. Dietary Met supplementation also exerted a protective effect against elevated hepatic enzyme levels (AST, P < 0.001; ALT, P < 0.001; ALP, P = 0.001; and LDH, P < 0.001) and serum uric acid levels (P < 0.001) induced by AFB1. Furthermore, dietary Met enhanced humoral immunity responses by increasing antibody production against sheep red blood cell antigen (P < 0.001) and hemagglutination inhibition response (P < 0.001), mitigating the AFB1-induced immune impairment. Meat quality parameters, including pH (P = 0.04), drip loss (P < 0.001), and malondialdehyde concentration (P < 0.001), were significantly influenced by the interaction between dietary Met and AFB1. Lastly, dietary Met supplementation effectively counteracted AFB1's detrimental effects on ileal lactic acid bacteria populations (P < 0.001). In conclusion, dietary Met supplementation shows promise as a nutritional intervention to alleviate the harmful effects of AFB1 exposure in Japanese quail, particularly in improving food quality and overall health.

Inna Rashkivska, Yana Kolianchuk, Mykola Prodanchuk et al.

The safety assessment of pinoxaden by the Joint Meeting on Pesticide Residues (JMPR) established a NOAEL of 30 mg/kg bw/day for maternal and embryo/fetal toxicity from a rabbit developmental toxicity study. However, the Pesticide Peer Review Expert meeting (EFSA) lowered the NOAEL to 10 mg/kg bw/day due to observed diaphragm malformations in one developmental toxicity study in rabbits, proposing a classification for developmental effects as Category 2 R63 or H361d. Both JMPR and EFSA set the Acceptable Daily Intake (ADI) at 0.1 mg/kg bw/day, derived from a 2-year rat study NOAEL with a safety factor of 100, but EFSA also supported ADI by teratology study in rabbits. The current prenatal developmental toxicity study on pinoxaden aimed to elucidate and clarify the potential teratogenic effects and could provide supplementary data for determining the ADI for pinoxaden. The study design exceeded the OECD TG 414 by including an assessment of internal organs. The test item was orally administered by gavage daily from day 6 to day 28 of gestation to three groups of animals, each composed of 21 females, in dose levels of 0, 10 and 30 mg/kg/bw/day. One female from the 30 mg/kg/bw/day dose group was euthanized in extremis on Day 27 post-coitum due to premature delivery, likely induced by poor general condition and was therefore considered to be an indirect effect of the test item. One female at 30 mg/kg/bw/day had entirely dead litters except for one live male pup (9 non-live implants vs 1 live fetus). Since the incidence of post-implantation loss or mean number of the dead pups within the remaining dams at 30 mg/kg/ bw/day that survived to necropsy was not significantly increased, we assume that the toxic effect was on the dam, rather than on the conceptus. No pinoxaden-related skeletal or visceral variations or malformations were observed. No evidence of developmental toxicity was observed. Under the conditions of the study, the pinoxaden produced maternal toxicity at a high dose tested; thus, NOAEL for maternal toxicity was determined to be 10 mg/kg bw/day. NOAEL for developmental toxicity was established at 30 mg/kg bw/day. The obtained results may supplement the overall safety and toxicity profile of pinoxaden. Nevertheless, the NOAEL determined in this study does not affect the previously established ADI.

Hiroshi Honda, Taisuke Kawamoto, Norio Imai et al.

Introduction We aimed to obtain the cell proliferation activity of tumor promoters in gastrointestinal (GI) organs following oral subacute incidental exposure to those promoters that do not target GI organs. Methods We conducted a 4-week repeated dose study using five-week-old Crl:CD(SD) rats (5 males/group), and selected sodium phenobarbital (PB) as a liver tumor promoter and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a skin tumor promoter. Male rats were given PB (100; 300; and 900 μg/mL) or TPA (0.5; 1.5; and 4.5 μg/mL) orally in drinking water for 28 days. Histopathological examination and bromodeoxyuridine (BrdU) immunostaining were conducted to examine the cell proliferation activity in the target organ (liver or skin) and GI organs. Results There was no death, and no treatment-related changes in clinical signs, body weight, and food and water consumption in the TPA and PB treated groups by a 28-day treatment. While no macroscopic changes were observed in the treatment groups, hepatocellular hypertrophy (5/5) was found at ≥100 μg/mL of PB as a treatment-related histopathological finding. No significant changes in BrdU labeling indices were observed in any organ/tissue examined including skin, liver, and GI organs both in TPA and PB treated groups. Conclusions Within our study, subacute oral exposure to a sufficient amount of tumor promoters (target organ: liver or skin) as contaminants in foods was not associated with cell proliferation in the target and GI organs. This finding may be helpful in qualitatively determining the carcinogenic risk of unexpected food contamination of carcinogenic promoters.

Legha Lotfollahi, Melika Golmohammadi, Farid Javandoust Gharehbagh et al.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs widely prescribed and used worldwide. Patients taking NSAIDs, including diclofenac, should be aware of its potential nephrotoxic effects. However, the rapid onset of acute kidney injury (AKI) after a single dose of diclofenac is considered a very rare side effect. Case Presentation: We present a 66-year-old woman with habitual self-induced anuria with the chief complaint of shoulder pain due to falling down. The patient presented with various co-morbid conditions, including hypertension, type 2 diabetes, tricuspid valve repair, and aortic valve replacement. She rapidly developed anuria after receiving a single dose of diclofenac over the previous two days of admission. Creatinine and BUN exhibited a significant rise in laboratory tests. During hospitalization, the consumption of NSAIDs was prohibited and losartan and furosemide were discontinued. Moreover, phenacetin was used to relieve pain instead. Luckily, after two days of hospitalization, urine output returned to normal levels. Additionally, creatinine and BUN levels gradually decreased to baseline values. Conclusion: To the best of our knowledge, we described a rare case of diclofenac-induced AKI presenting with anuria, a complete cessation of urine flow, in a patient with no previous kidney complications. This case can be explained by the phenomenon known as “quadruple Whammy,” which involves the concurrent use of NSAIDs, ARBs, and diuretics in the setting of hypovolemia.

Zahrasadat Roholamini, Mehdi Abbaspoor, Soheil Aminizadeh et al.

Background and objective: Lithium medication, given its significant role in the treatment or reduction of psychiatric disorders, may exert adverse effects on cardiac tissue. Therefore, this study aimed to investigate the effects of different exercise training intensities on the process of cardiac apoptosis and serum levels of cardiac troponin I (cTnI) resulting from lithium administration in male Wistar rats. Methodology: In the present experimental study, 35 male Wistar rats were randomly divided into five groups (n=7); Control (CTL), Lithium (Li), High-Intensity training + lithium (HIT-Li), Moderate-Intensity training + lithium (MIT-Li), and Low-Intensity training + lithium (LIT-Li). Lithium drug (dose of 40 mmol/kg dry food weight) and exercise training (5 days per week) were administered for eight weeks. Serum levels of cTnI, mRNA expression of Bcl-2, Bax, and Caspase-3, and histopatholigical changes were assessed by using the ELISA method, Real-Time PCR, and H&E staining, respectively. Results: The expression of the Bcl-2 gene was significantly increased in the LIT-Li group compared to the Li group (P = 0.003). Serum levels of cTnI were considereably higher in the Li group compared to the MIT-Li group (P = 0.0001). The expression of the Bax gene, in the LIT-Li, HIT-L, and Li groups, significantly increased compared to the MIT-Li group (P = 0.0001). Histopathological scores decreased in MIT-Li compared to Li group (P = 0.001). Conclusion: It seems that among different exercise intensities, the greatest protective effect against lithium consumption can be observed with moderate exercise intensity, which may potentially modulate factors influencing cardiac apoptosis and reduce lithium toxicity in the cardiac tissue of rats.

Hee-Yon Park, Christopher Chung, Madeline K. Eiken et al.

Introduction: Biomolecules bind to and transform nanoparticles, mediating their fate in biological systems. Despite over a decade of research into the protein corona, the role of protein modifications in mediating their interaction with nanomaterials remains poorly understood. In this study, we evaluated how glycation of the most abundant blood protein, human serum albumin (HSA), influences the formation of the protein corona on 40 nm silver nanoparticles (AgNPs) and the toxicity of AgNPs to the HepG2 human liver cell line.Methods: The effects of glycation on AgNP-HSA interactions were quantified using circular dichroism spectroscopy to monitor protein structural changes, dynamic light scattering to assess AgNP colloidal stability, zeta potential measurements to measure AgNP surface charge, and UV-vis spectroscopy and capillary electrophoresis (CE) to evaluate protein binding affinity and kinetics. The effect of the protein corona and HSA glycation on the toxicity of AgNPs to HepG2 cells was measured using the WST cell viability assay and AgNP dissolution was measured using linear sweep stripping voltammetry.Results and Discussion: Results from UV-vis and CE analyses suggest that glycation of HSA had little impact on the formation of the AgNP protein corona with protein-AgNP association constants of ≈2x107 M-1 for both HSA and glycated HSA (gHSA). The formation of the protein corona itself (regardless of whether it was formed from HSA or glycated HSA) caused an approximate 2-fold decrease in cell viability compared to the no protein AgNP control. While the toxicity of AgNPs to cells is often attributed to dissolved Ag(I), dissolution studies showed that the protein coated AgNPs underwent less dissolution than the no protein control, suggesting that the protein corona facilitated a nanoparticle-specific mechanism of toxicity. Overall, this study highlights the importance of protein coronas in mediating AgNP interactions with HepG2 cells and the need for future work to discern how protein coronas and protein modifications (like glycation) may alter AgNP reactivity to cellular organisms.

Zahra Chaharbaghi, Aliyar Fallah

INTRODUCTION Regular physical activity has many health benefits, including prevention of chronic diseases and premature deaths, improvement of physical and mental health, and better cognitive function [1-4]. ... [5]. Research data show that adults do not have adequate levels of physical activity, which can jeopardize their current and future health [6-9]. ... [7]. In Iran, not many types of research have been conducted regarding the amount of participation of adults in physical activity, but these few types of research indicate the low level of moderate to severe physical activity of adults [10]. One of the groups in the age group of adults, who should participate in regular physical activity due to the nature of their job and maintaining their physical and mental health, are the personnel of police Headquarter. Quality of life is one of the factors in which participation in physical activity has been effective in different age groups, including adults [11-13]. Health-related quality of life focuses on the subjective perception of adults, their health status, and their ability to perform daily activities in different areas of life [14-17]. Systematic review evidence suggests that higher levels of physical activity are associated with higher health-related quality of life scores [18]. However, the relationship between physical activity and quality of life in police command staff has not been investigated and this issue needs to be investigated. In addition, evidence has shown that physical activity is associated with well-being [16, 19]. Well-being is not only related to the absence of disease, but it is a complex combination of physical, mental, emotional, and social health factors of a person [20]. AIM(S) The purpose of this research was to determine the level of physical activity of the employees of the Great Tehran Police Headquarter and to investigate the relationship between physical activity and the quality of life related to their health and well-being by emphasizing gender differences. RESEARCH TYPE This research method is descriptive correlation based on structural equations. RESEARCH SOCIETY, PLACE & TIME The statistical population of this research was all employees of Great Tehran Police Headquarter (including the traffic police, police stations, and Fateb Headquarters) in 2021. SAMPLING METHOD AND NUMBER The statistical sample of this research was 186 men and women using Cochran's formula by available sampling method. USED DEVICES & MATERIALS Physical activity was measured using the short form of the International Physical Activity Questionnaire (IPAQ) [21]. This questionnaire is suitable for determining the physical activity of adults aged 18-65 years, and its validity and reliability have been reported very well [22]. In this research, the validity of this questionnaire was confirmed by eight experts. Also, Cronbach's alpha coefficient of this questionnaire was 0.92. The cut-off point for different classes of physical activity states that each adult should preferably have 30 minutes of moderate-intensity physical daily activity in a week [22]. Health-related quality of life was measured using the SF-12 questionnaire. This questionnaire is a general tool for measuring the health status of people 14 years and older. The minimum and maximum scores of this test are between 0 and 100, which means that the closer the subject's score is to 100, the higher the health-related quality of life and vice versa. This questionnaire has been used many times in Iran and has high validity and reliability [23]. In this research, the validity of this questionnaire was confirmed by eight experts. Also, Cronbach's alpha coefficient was 0.88. The cut-off point of this questionnaire is 46, which indicates the physical and mental health status of a person [23]. In this research, the well-being variable was measured using the Adult Well-Being Assessment Questionnaire (AWA), which is a valid survey to assess the physical and mental well-being of adults [24]. In this study, the validity of this questionnaire was confirmed by eight experts. Also, Cronbach's alpha coefficient was equal to 0.86. The cut-off point of this questionnaire is 5, which indicates a person's sense of normal well-being [24]. METHOD The method of conducting the research was in a way that after coordinating with the officials of the Great Tehran Police Headquarter, the research questionnaires were distributed among the employees, and the people who were willing to participate in the research completed and submitted the questionnaires. ETHICAL PERMISSION To comply with the ethical standards, the ethical principles including the introduction of the research, the objectives, and method of conducting the research, and the privacy policy were presented to the participants. STATISTICAL ANALYSIS The Kolmogorov–Smirnov test was used to check the normality of the research data. Pearson's correlation test and structural equations were used for the inferential analysis of relationships between research analyses. Differences between men and women were analyzed using an independent t-test. The significance level was considered at 0.05. Data were analyzed using SPSS 26 and Lisrel 8.8 software. FINDING by TEXT Out of 186 sample participants in this research, 93 people were from police stations, 71 people were from traffic police and 22 people were from Fateb Headquarters. As the most important index in the subject's profile, the body mass index of men (23.80±1.36) is higher than women (22.63±1.75) (Table 1). Although the body mass index was normal in both genders, it was very close to the overweight level in men. Men had a higher level of physical activity than women (Table 2). The results showed that 54% of men and 52% of women had moderate to intense physical activity. Also, health-related quality of life scores was almost the same in both genders and was in the average range (t=0.25; p=0.942). Finally, the well-being scores of men and women were the same and were in the average range (t=0.42; p=0.785; Table 2). The results of the Kolmogorov-Smirnov test showed that the research data had a normal distribution (p>0.05). The results of the independent t-test showed that men compared to women in the number of days they did the physical activity (t=1.93; p=0.015) and also the number of minutes they did physical activity during the week (t=6.27; p<0.001) had significant superiority (Table 2). The results of Pearson's correlation coefficient to investigate the two-way relationship between the research variables showed that there is a relationship between health-related quality of life and physical activity (days per week and minutes per week, respectively, r=0.621 and r=0.416) and also there was a significant relationship with physical activity intensity (r=0.737), (p<0.001). Also, there was a significant relationship between physical activity (days per week and minutes per week, respectively, r=0.517 and r=0.582) and intensity of physical activity (r=0.326), with well-being (p<0.001). The relationship between health-related quality of life and well-being was also significant (r=0.361; p<0.001). The results of the structural equation method also confirmed the significance of the causal relationships between the research variables (Table 3 and Chart 1). The results of fitting the research model are given in Table 4. According to the results, the current research model had a good fit (RMSEA=0.07). MAIN COMPARISION to the SIMILAR STUDIES On average, the results showed that men and women had a lower level of physical activity than the value recommended by WHO of 60 minutes of moderate-to-severe physical activity. Also, the results showed that half of the personnel of the Tehran police Headquarter did not have suitable physical activity for physical and mental health. These results are consistent with the findings of previous research [6-9] and indicate the relatively low level of physical activity of the personnel of the Tehran police Headquarter. Regarding gender differences in physical activity, the results of this research showed that men participated significantly more than women in physical activity. These results are consistent with previous findings [26-28] and indicate that strategies to promote physical activity among police headquarter personnel should have a special emphasis on women's physical activity. ... [29, 30]. The results of the research showed that health-related quality of life in Tehran police Headquarter personnel was at an average level, which are consistent with the previous studies by Dosic et al., Zhang et al., Lee C and Russell, as well as the study by Rejeski and Mihalko [14-17] and indicate relatively low levels of health-related quality of life among adults. The average level of health-related quality of life in police headquarter personnel is probably related to job difficulty or financial components. In addition, no significant gender difference was observed regarding health-related quality of life. These findings are not following the results of previous studies and show that men had a relatively better perception of quality of life than women [18]. These differences may be due to the relatively difficult working conditions of the male and female police headquarter personnel. The results of structural equation modeling showed that greater participation in physical activity had a positive and significant effect on health-related quality of life in police headquarter personnel; these findings are following the results of previous studies [14-18]. Therefore, physical activity is related to the improvement of the quality of life in police headquarter personnel. Regarding well-being, the results of the research showed that the perception of well-being among the employees of Tehran Police headquarter was at an average level. The present findings are consistent with the findings of Lee and Russell's study as well as Fox et al.'s study [16, 19]. Similar to the perception of quality of life, the average level of well-being in police headquarter personnel can also be related to job difficulty or financial components. Similar to the quality of life, no significant gender difference was observed regarding the perception of well-being. These findings are not following the results of previous studies that showed that men had a relatively better perception of well-being than women [16, 19], which could mainly be related to the relatively difficult working conditions of both male and female police headquarter personnel. The results of structural equation modeling showed that greater participation in physical activity had a positive and significant effect on the sense of well-being in police headquarter. These findings are following the results of previous studies [16, 19]. Physical activity can improve people's well-being by influencing the individual's standards and opinions in life and promoting independence, control, and mastery over the surrounding environment. Doing physical activity not only improves the physical condition but also improves the personality, psychological and social dimensions. In addition, exercise and physical activity are effective in expressing emotions and feelings, also increasing self-confidence and a sense of hope and humor [16, 17]. All these components can be considered part of a person's well-being. LIMITATION One of the limitations of the present study was that physical activity was measured using a self-report questionnaire, which can be biased. Also, the socio-economic status of the research subjects was not investigated. SUGGESTIONS Socio-economic status can be one of the factors affecting people's participation in physical activity and its consequences such as physical and mental health. It is suggested that in future research, physical activity be measured using accelerometer tools that objectively measure physical activity. It is also suggested that the socio-economic status of employees and its relationship with their participation in physical activity be investigated. CONCLUSIONS The physical activity of police headquarter personnel is less than the World Health Organization's recommended of 60 minutes of moderate-to-severe physical activity per day, and women also have less physical activity than men. Also, physical activity has a positive effect on the quality of life and well-being of police headquarter, which highlights the role of regular physical activity in improving the quality of life of these employees. ACKNOWLEDGMENTS We thank all the personnel of the Police headquarter who participated in this research. CONFLICT of INTEREST The authors state that there is no conflict of interest in the present study. FUNDING SOURCES This study had no financial support.

Lokeshwari Natarajan, Das Soupam, Swarnali Dey et al.

Microplastics (MPs) are perpetual contaminants that are mostly generated by human activity and are deposited in aquatic ecosystem. MPs may react differently in aquatic organisms depending on their size, surface charge, and concentration. The current investigation examined the interactions of polystyrene (PS) microplastics (of varied charges and sizes) with Scenedesmus obliquus, a unicellular phytoplankton. It is observed that 1 µm PS-MPs produced increased oxidative stress than 12 µm PS-MPs as indicated by total reactive oxygen species (ROS), superoxide and hydroxyl radical generation, and lipid peroxidation results. Additionally, decreased photosynthetic effectiveness, membrane integrity and esterase activity were also observed for the lower sized MPs. Antioxidant enzyme activities like superoxide dismutase (SOD) activity and catalase (CAT) activity correlated well with the oxidative stress generation in the cells. The effects by both the sizes of MPs were dose dependent in nature. Given the importance of a rapidly developing scientific literature on the effects of MPs in freshwater organisms, understanding the dynamics of interactions with lower-level organisms becomes very relevant.

Farzad Gheshlagh, Anselm Wong, Gholamali Dorooshi et al.

Background: Digoxin is extensively prescribed for cardiac diseases, so its chronic or acute toxicity commonly occur. Although digoxin specific antibodies (anti-digoxin Fab) are recommended to be used in patients with cardiac symptoms of digoxin toxicity, there is ongoing controversy about the effectiveness and dose of anti-digoxin Fab. Because our department lacks access to anti-digoxin Fab and the high cost of the antidote, we evaluated 10 years of experience in treating patients with digoxin toxicity without using digoxin Fab antibodies considering outcomes.Methods: A retrospective study was performed in Khorshid Hospital, affiliated with Isfahan University of Medical Sciences, from October 2008 to September 2018. Patients with acute or chronic digoxin toxicity were included in the study. The patients’ data were gathered and analyzed according to their medical documents.Results: Out of 150 cases with digoxin toxicity, 38% (n=57) were acute and 62% (n=93) were chronic. About 64.7% (n=97) were female. The most common non-cardiac manifestations of toxicity were gastrointestinal (67.3%, n=101) and neurological symptoms (52.7%, n=79). Bradyarrhythmia (80.5%, n=33) was the most cardiac manifestation in patients with acute (15.8% n=9) and chronic (25.8%, n=24) toxicity. A total of 144 (96%) cases fully recovered with supportive care, and 6 patients (4%) died. None of the cases received anti-digoxin Fab.Conclusion: The majority of presentations with acute or chronic toxicity recovered with supportive measures without using anti-digoxin Fab

Sean Cuninghame, Khaled Lotfy, Paul Cameron

Massive Acetaminophen (N-acetyl-p-aminophenol; APAP) overdose is a common presentation to emergency departments around the world. While N-acetylcysteine (NAC) remains the cornerstone of treatment for APAP overdose, extracorporeal treatment, in the form of renal replacement therapy with intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT) may provide benefit in cases associated with altered mental status and metabolic acidosis. One treatment with IHD is typically sufficient for resolution of acidosis and global improvement clinically. We describe a case of massive APAP overdose presenting with altered mental status and lactic acidosis, refractory to multiple treatments of IHD as well as CRRT and high-dose NAC along with fomepizole. Despite these interventions, fulminant liver failure progressed with cerebral edema, coagulopathy and death. This is the first description of a fatal acetaminophen ingestion refractory to both IHD and prolonged CRRT. This case highlights the need for further investigation in the management of massive APAP overdose, including optimal method and timing of renal replacement therapy.

W. M. Dimuthu Nilmini Wijeyaratne, P. G. Minola Udayangani Wickramasinghe

Appropriate effluent treatment processes are expected to significantly reduce the toxicity of effluents before they are released to the natural environment. The present study was aimed to assess the spatial and temporal variations of the physical and chemical water quality parameters of a natural water body receiving treated textile effluents and to assess the chromosomal abnormalities induced by the treated textile effluents. Four sampling sites (A: effluent discharge point; B: 100 m downstream from site A along the tributary; C: 200 m downstream from site A along the tributary; D: 100 m upstream from site A along the tributary) were selected associated to a tributary that received treated textile effluent. The physical and chemical water quality parameters were measured in the composite water samples collected from the study sites, and Allium cepa bioassay was conducted using aged tap water as the control. Sampling was conducted in both rainy and dry seasons. The conductivity, TDS, COD, and colour intensity of the water samples collected from the study sites were significantly higher during the dry season compared to those in the rainy season. Allium cepa root meristematic cells exposed to water samples from sites A, B, and C showed a significantly high interphase and prophase indices compared to those exposed to aged tap water and upstream site during both rainy and dry seasons. The mitotic index of the root tip cells of Allium cepa bulbs exposed to the water samples collected from the effluent discharge point (site A) and from the 100 m downstream site from site A (site B) was significantly lower than that of the other sites in both rainy and dry seasons. However, the mitotic index of the root tip cells of Allium cepa bulbs exposed to the water samples from the upstream site was not significantly different from that of the control treatment during both sampling seasons. The bioassay indicated that the mitotic index and phase index of the root meristematic cells of Allium cepa can be affected by the treated textile effluents released to the water body and the occurrence of C metaphase, chromosomal adherence, bridges, disturbed anaphase, vagrant chromosomes, and chromosomal breaks indicated that the treated textile effluent receiving tributary can possibly contain genotoxic and mutagenic compounds which can induce chromosomal abnormalities.

Angelika Długosz-Pokorska, Marlena Pięta, Jacek Kędzia et al.

Abstract Background 5-Fluorouracil (5-FU) is an antimetabolite that interferes with DNA synthesis and has been widely used as a chemotherapeutic drug in various types of cancers. However, the development of drug resistance greatly limits its application. Overexpression of ATP-binding cassette (ABC) transporters in many types of cancer is responsible for the reduction of the cellular uptake of various anticancer drugs causing multidrug resistance (MDR), the major obstacle in cancer chemotherapy. Recently, we have obtained a novel synthetic 5-FU analog, U-332 [(R)-3-(4-bromophenyl)-1-ethyl-5-methylidene-6-phenyldihydrouracil], combining a uracil skeleton with an exo-cyclic methylidene group. U-332 was highly cytotoxic for HL-60 cells and showed similar cytotoxicity in the 5-FU resistant subclone (HL-60/5FU), in which this analog almost completely abolished expression of the ATP-binding cassette (ABC) transporter, multidrug resistance associate protein 1 (ABCC1). The expression of ABC transporters is usually correlated with NF-κB activation. The aim of this study was to determine the level of NF-κB subunits in the resistant HL-60/5-FU cells and to evaluate the potential of U-332 to inhibit activation of NF-κB family members in this cell line. Methods Anti-proliferative activity of compound U-332 was assessed by the MTT assay. In order to disclose the mechanism of U-332 cytotoxicity, quantitative real-time PCR analysis of the NF-κB family genes, c-Rel, RelA, RelB, NF-κB1, and NF-κB2, was investigated. The ability of U-332 to reduce the activity of NF-κB members was studied by ELISA test. Results In this report it was demonstrated, using RT-PCR and ELISA assay, that members of the NF-κB family c-Rel, RelA, RelB, NF-κB1, and NF-κB2 were all overexpressed in the 5-FU-resistant HL-60/5FU cells and that U-332 potently reduced the activity of c-Rel, RelA and NF-κB1 subunits in this cell line. Conclusions This finding indicates that c-Rel, RelA and NF-κB1 subunits are responsible for the resistance of HL-60/5FU cells to 5-FU and that U-332 is able to reverse this resistance. U-332 can be viewed as an important lead compound in the search for novel drug candidates that would not cause multidrug resistance in cancer cells.

Ki-Young Kang, Min-Sub Kim, Min-Seung Lee et al.

l-threonine, l-tryptophan and l-valine play a fundamental role in animal and human nutrition as essential amino acids required for normal growth. In addition, each amino acid is codified as a generally recognized as safe (GRAS) amino acid for the use in animal feed additives and presents no exposure risk from animal to humans consuming tissues or products from the target animal. Taking into account the important role of mutagenicity and genotoxicity in the risk of the three amino acid additives (l-threonine, l-tryptophan, and l-valine) fermentation products and other unknown impurities and derivatives from Corynebacterium glutamicum (C. glutamicum), the safety evaluation of these amino acid additives is not performed. Therefore, the purpose of this study is to evaluate toxicological effects, including Ames test, an in vitro mammalian chromosomal aberration test and an acute oral animal toxicity of the three amino acid additives in accordance with the Organisation for Economic Co-operation and Development (OECD) guidelines and the principles of Good Laboratory Practice (GLP). As a result, these amino acid additives were classified as non-mutagenic and non-clastogenic, and did not induce any toxicity in acute oral toxicity test. Collectively, these results suggest that the three amino acid additives are safe with no adverse effects, and able to be applied as an ingredient or other biological uses.

Trevonne M. Thompson, Jillian Theobald, Jenny J. Lu et al.

Aiping Zhang, Kitipong Uaesoontrachoon, Conner Shaughnessy et al.

Phosphorodiamidate morpholino oligonucleotides (PMO) are used as a promising exon-skipping gene therapy for Duchenne muscular dystrophy (DMD). One potential complication of high dose PMO therapy is its transient accumulation in the kidneys. Therefore new urinary biomarkers are needed to monitor this treatment. Here, we carried out a pilot proteomic profiling study using stable isotope labeling in mammals (SILAM) strategy to identify new biomarkers to monitor the effect of PMO on the kidneys of the dystrophin deficient mouse model for DMD (mdx-23). We first assessed the baseline renal status of the mdx-23 mouse compared to the wild type (C57BL10) mouse, and then followed the renal outcome of mdx-23 mouse treated with a single high dose intravenous PMO injection (800 mg/kg). Surprisingly, untreated mdx-23 mice showed evidence of renal injury at baseline, which was manifested by albuminuria, increased urine output, and changes in established urinary biomarker of acute kidney injury (AKI). The PMO treatment induced further transient renal injury, which peaked at 7 days, and returned to almost the baseline status at 30 days post-treatment. In the kidney, the SILAM approach followed by western blot validation identified changes in Meprin A subunit alpha at day 2, then returned to normal levels at days 7 and 30 after PMO injection. In the urine, SILAM approach identified an increase in Clusterin and γ-glutamyl transpeptidase 1 as potential candidates to monitor the transient renal accumulation of PMO. These results, which were confirmed by Western blots or ELISA, demonstrate the value of the SILAM approach to identify new candidate biomarkers of renal injury in mdx-23 mice treated with high dose PMO.

Mohammad Reza Khazdair

Nigella sativa (N. sativa) is an annual plant and widely used as medicinal plant throughout the world. The seeds of the plant have been used traditionally in various disorders and as a spice to ranges of Persian foods. N. sativa has therapeutic effects on tracheal responsiveness (TR) and lung inflammation on induced toxicity by Sulfur mustard. N. sativa has been widely used in treatment of various nervous system disorders such as Alzheimer disease, epilepsy, and neurotoxicity. Most of the therapeutic properties of this plant are due to the presence of some phenolic compounds especially thymoquinone (TQ), which is major bioactive component of the essential oil. The present review is an effort to provide a comprehensive study of the literature on scientific researches of pharmacological activities of the seeds of this plant on induced neurotoxicity.

D. Jang, M. Spyres, L. Fox et al.

S. Shyaula

The tuberous roots of genus Aconitum are commonly applied for various diseases, such as rheumatic fever, painful joints and some endocrinal disorders. It stimulates the tip of sensory nerve fibers. These tubers of Aconitum are used in the herbal medicines only after processing. At the mean time, there remain high toxicological risks of the improper usages of Aconitum . The cardio- and neurotoxicity of this herb are potentially lethal. Some of the species like A. ferox and A. spicatum are deadly poisonous while others like A. oreochryseum and A. bisma are used as the antidote for Aconitum poisoning. It is therefore, a valuable drug as well as an unpredictable toxic material. In the current review, assessments of Aconitum species are carried out, to increase knowledge for the safety uses, in context of Nepal. The traditional uses, phytochemical studies, its processing techniques and toxicological principles are reviewed. DOI:  http://dx.doi.org/10.3126/njst.v12i0.6496 Nepal Journal of Science and Technology 12 (2011) 171-178

R. Dinis-Oliveira, F. Carvalho, J. Duarte et al.