Effect Of Aflatoxin B1 Exposure Research Articles

Effect of Aflatoxin-B1 Exposure on Performance and Haematological Stress Indicators in Male Sprague Dawley Rats

Effect of Aflatoxin-B1 Exposure on Performance and Haematological Stress Indicators in Male Sprague Dawley Rats

Effect of aflatoxin B1 exposure on the progression of depressive-like behavior in rats.

While it is well documented that aflatoxin B1 (AFB1); one of the most toxic food contaminants is linked to the development of depression. However, the mechanism on how it affects the gut and brain health leading to depressive-like behavior remains unclear. This study was conducted to determine the effect of AFB1 on the progression of depressive-like behavior. Thirty-two (n = 32) male Sprague Dawley rats were randomly allocated into four groups: control, low-dose (5 μg AFB1/kg), high-dose (25 μg AFB1/kg) and positive control group; exposed on chronic unpredictable mild stress (CUMS). After 4 weeks of exposure, sucrose preference test (SPT) and force swim test (FST) were used to measure behavioral despair. Fecal samples were selectively cultured to profile the bacteria. Body weight and relative organs weights were compared among groups. AFB1 and CUMS caused reduction in body weight and food intake as well as increased relative weight of adrenal glands, liver, and brain. Rats in AFB1 and CUMS groups had suppressed sucrose preference and prolonged immobility time in FST, wherein this could indicate anhedonia. Besides, fecal count of Lactobacillus spp. was significantly low following AFB1 exposure, with increasing count of Bifidobacterium spp, in comparison to the control. Indeed, further biochemical analysis and metagenomic approach are warranted to explore the underlying mechanisms on the role of gut microbiota dysbiosis and dysregulation of gut-brain axis due to AFB1 neurotoxicity on the progression of depressive-like behavior.

The Effect of Aflatoxin B1 on Tumor-Related Genes and Phenotypic Characters of MCF7 and MCF10A Cells.

The fungal toxin aflatoxin B1 (AB1) and its reactive intermediate, aflatoxin B1-8, 9 epoxide, could cause liver cancer by inducing DNA adducts. AB1 exposure can induce changes in the expression of several cancer-related genes. In this study, the effect of AB1 exposure on breast cancer MCF7 and normal breast MCF10A cell lines at the phenotypic and epigenetic levels was investigated to evaluate its potential in increasing the risk of breast cancer development. We hypothesized that, even at low concentrations, AB1 can cause changes in the expression of important genes involved in four pathways, i.e., p53, cancer, cell cycle, and apoptosis. The transcriptomic levels of BRCA1, BRCA2, p53, HER1, HER2, cMyc, BCL2, MCL1, CCND1, WNT3A, MAPK1, MAPK3, DAPK1, Casp8, and Casp9 were determined in MCF7 and MCF10A cells. Our results illustrate that treating both cells with AB1 induced cytotoxicity and apoptosis with reduction in cell viability in a concentration-dependent manner. Additionally, AB1 reduced reactive oxygen species levels. Phenotypically, AB1 caused cell-cycle arrest at G1, hypertrophy, and increased cell migration rates. There were changes in the expression levels of several tumor-related genes, which are known to contribute to activating cancer pathways. The effects of AB1 on the phenotype and epigenetics of both MCF7 and MCF10A cells associated with cancer development observed in this study suggest that AB1 is a potential risk factor for developing breast cancer.

English

Gestational and lactational transmission of Aflatoxin B1 (AFB1) can elicit several toxic effects emphasizing the severity of aflatoxicosis. The present study aimed to investigate the genotoxic effects of prenatal and postnatal exposure to AFB1 on the livers of exposed offspring. With this aim, 50 μg/kg/body weight per day AFB1 was administered intraperitoneally (i.p.) to pregnant and lactating dam rats. Pups grouped as newborns (GD21/PND0) exposed in utero and infants exposed through breast milk (PND21) were compared with body weight measurements. Liver tissues were weighed after removal and subjected to histochemical (HC), immunohistochemical (IHC) and biochemical analyzes. The body weight and liver weight of exposed newborns were significantly lower than control (P<0.05). The histomorphological changes were more pronounced in exposed newborns. A decrease (P<0.05) in the histological score (HSCORE) of cytokeratin 19 (CK19) IHC, fetal stem/progenitor cells marker, and an increase (P<0.05) in the HSCORE of alpha-fetoprotein (AFP) IHC, hepatocellular carcinoma (HCC) marker, were detected in both exposed groups. Exposed newborns showed higher CK19 and AFP HSCORE than exposed infants (P<0.05). Both groups exhibited a low proliferation index score of proliferating cell nuclear antigen (PCNA) IHC (P<0.05). The high apoptotic index score of immunofluorescence (IF) staining of the terminal deoxytransferase-mediated dUTP nick-end labeling (TUNEL) method was significant in exposed newborns (P<0.05). Evaluation of oxidative stress and antioxidant systems revealed that tissue malondialdehyde (MDA) levels decreased in exposed newborns and increased in exposed infants (P<0.05), and tissue catalase (CAT) levels increased in both groups (P<0.05). In conclusion, the effects of AFB1 exposure during the gestational period occurred more severely, and the importance of preventing AFB1 exposure was revealed

Aflatoxin B1 as a Threshold Concept of Uncertain Etiology of Chronic Kidney Diseases

A case control study was conducted in karbala province to investigate aflatoxin B1 (AFB1) exposure among the chronic kidney disease (CKD) patients and healthy control. AFB1 level were measured qualitatively by Thin layer chromatography and quantitatively by high-performance liquid chromatography.The assessment of positive AFB1 samples were evaluated along with biomarkers of renal functions tests.The results showed that the investigated population were exposed to Aflatoxins. AFB1 was detected in 100% of uncertain CKD patients and 24%, 20% in certain CKD patients and healthy control respectively. The concentration ranges in serum samples were 0.68 –8.33 ng/mL for uncertain CKD patients, 1.21-5.60 ng/mL for certain CKD patients and 0.11- 1.30 ng/mL for healthy control. The un-certain etiology of CKD patients had a significant associations of decreasing GFR and increasing the levels of urea, creatinine with positive serum AFB1. This association was also highly interest with regard to potential interactions with Urea levels in the control group. The measurement of the AFB1 in serum samples of CKD patients and healthy control were indicated a long term exposure to the toxin which result in uncertain etiology of CKD. The effect of AFB1 exposure was confirmed through the assessment of the biochemical marker of renal tests. This study can be a good establish of a national AFs exposure monitoring programs. Also the study highlighted the needing to identify the pathogenesis of contribution AFB1 in the increasing number of uncertain CKD patients. Future study is encouraged to focus on broader areas which cover the whole of country.

Toxic Effect of Aflatoxin B1 on Heart, Lung, and Testis of Male Albino Rats: Histopathology Study

The current study was carried out to investigate the toxic effects of aflatoxin B1 exposure on heart, lung, and testis of male Albino rats. Twelve healthy male Albino rats were used in the current study. They were divided equally into 2 groups (control and treated groups). The treated group was given aflatoxin B1 orally by a gastric tube at concentration 0.5 mg per kg of body weight for 7 day. The control group was given distilled water alone. At the end of experiment (1 week), the rats were killed under ether anesthesia and the internal organs(heart, lung, and testis) were collected immediately for histological examination. The histopathology examination in heart revealed that there is oedema between myocardial. In lung, there is a large number of inflammatory cells and dilated the alveolar sac with exudates. The testis revealed the excessive vacuolated cells and suppression spermatogenesis. In conclusion, oral dose of aflatoxin B1 exposure could induce a deleterious effect on the histological structure of the heart, lung, and testis of male Albino rats. High level of attention must be taken to prevent the possible contamination of our food with aflatoxin B1.

Effects of aflatoxin B1 exposure and sodium selenite supplementation on the histology, cell proliferation, and cell cycle of jejunum in broilers.

The aim of this study was to investigate the effects of aflatoxin B1 (AFB1) exposure and sodium selenite supplementation on the histology, cell proliferation and cell cycle of jejunum in broilers. A total of 240 1-day-old male AA broilers were divided into four groups of 60 each, fed with basal diet (control group), 0.3 mg/kg AFB1 (AFB1 group), 0.4 mg/kg supplement Se (Se group), and 0.3 mg/kg AFB1 + 0.4 mg/kg supplement Se (AFB1 + Se group) for 21 days, respectively. Compared with the control group, decreased jejunal villus height, villus height/crypt ratio, and proliferation cell nuclear antigen (PCNA)-positive cells, and G2/M phase arrest and shedded epithelial cells on the tip of jejunal villus were observed in AFB1 groups at 7 and 14 days of age. However, the villus/crypt ratio, PCNA-positive cells and cell percentage of G0/G1, S, and G2/M phases had no significant differences between AFB1 group and control group at 21 days. Simultaneous supplementation with sodium selenite restored these parameters to be close to those in control group. In conclusion, 0.3 mg/kg AFB1 in the diet inhibits the development of broiler's jejunum by reducing cellular proliferation and inducing G2/M arrest during only the first 2 weeks after hatching. Supplementation of dietary sodium selenite at the concentration of 0.4 mg/kg Se had protective action against these toxic effects of AFB1.

Abstract 4161: Synergistic effects of aflatoxin B1 exposure and glycine N-methyltransferase deficiency in hepatocarcinogenesis

Abstract In both humans and rodents, males are known to be more susceptible than females to hepatocarcinogenesis. We have previously reported that glycine N-methyltransferase (GNMT) interacts with aflatoxin B1 (AFB1) and reduces both AFB1-DNA adduct formation and hepatocellular carcinoma (HCC) in mice. We also reported that 50% of the males and 100% of the females in a small group of Gnmt null (Gnmt−/−) mice developed HCC, with first liver nodules detected at mean ages of 17 and 16.5 months, respectively. In this study we tested our hypothesis that male and female Gnmt−/− mice are susceptible to AFB1 carcinogenesis, and that the absence of Gnmt expression may accelerate AFB1-induced liver tumorigenesis. We inoculated Gnmt−/− and wild-type mice intraperitoneally with AFB1 at 7 days and 9 weeks of age and periodically examined them using ultrasound. Liver nodules were detected in 6 of 8 males and 5 of 5 females at 12.7 and 12 months of ages, respectively. Liver nodules from 5/8 (62.5%) male and 4/5 (80%) female Gnmt−/− mice were diagnosed as having HCC, approximately 6 months earlier than AFB1-treated wild-type mice. Results from microarray and real-time PCR analyses indicate that five detoxification pathway-related genes were down-regulated in AFB1-treated Gnmt−/− mice: Cyp1a2, Cyp3d44, Cyp2d22, Gsta1 and Abca8a. In summary, we observed a synergistic relationship between GNMT deficiency and AFB1 exposure in hepatocarcinogenesis, further evidence that GNMT over-expression is an important contributing factor to female liver cancer resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4161.

The effect of aflatoxin B1 exposure on serotonin metabolism: response to a tryptophan load.

Semi-chronic exposure of ICR male Mice to Aflatoxin B1 (AFB1) in non-toxic doses decreased brain serotonin (5-hydroxytryptamine, 5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA) and catecholamines without altering tryptophan (TRP) or tyrosine (TYR) levels. A TRP load (300 mg/kg, i.p. x 2 hours) slightly increased brain TRP levels while causing a slight decrease in 5-HT and 5-HIAA in control animals. A TRP load in AFB1 treated mice increased brain 5-HT and 5-HIAA. The TRP load caused a further reduction in brain catecholamines without altering TYR levels. Exposure to AFB significantly increased lung TRP levels without altering 5-HT or 5HIAA levels. TRP loading increased lung TRP concentrations in control mice. However, in AFB1 treated mice the increase was not significantly elevated above the level caused by AFB1 treatment alone. Lung 5-HT or 5-HIAA levels in control or AFB1 treated mice are not significantly altered by TRP loading. These experiments demonstrate that AFB1 alters brain and lung TRP metabolism.