Bibliography Tag: liver damage

Bibliography Index

Hued, 2012

Hued, Andrea Cecilia, Oberhofer, Sabrina, & de los Ángeles Bistoni, María; “Exposure to a Commercial Glyphosate Formulation (Roundup®) Alters Normal Gill and Liver Histology and Affects Male Sexual Activity of Jenynsia multidentata (Anablepidae, Cyprinodontiformes);” Archives of Environmental Contamination and Toxicology, 2012, 62(1), 107-117; DOI: 10.1007/s00244-011-9686-7.

ABSTRACT:

Roundup is the most popular commercial glyphosate formulation applied in the cultivation of genetically modified glyphosate-resistant crops. The aim of this study was to evaluate the histological lesions of the neotropical native fish, Jenynsia multidentata, in response to acute and subchronic exposure to Roundup and to determine if subchronic exposure to the herbicide causes changes in male sexual activity of individuals exposed to a sublethal concentration (0.5 mg/l) for 7 and 28 days. The estimated 96-h LC50 was 19.02 mg/l for both male and female fish. Gill and liver histological lesions were evaluated through histopathological indices allowing quantification of the histological damages in fish exposed to different concentrations of the herbicide. Roundup induced different histological alterations in a concentration-dependent manner. In subchronic-exposure tests, Roundup also altered normal histology of the studied organs and caused a significant decrease in the number of copulations and mating success in male fish exposed to the herbicide. It is expected that in natural environments contaminated with Roundup, both general health condition and reproductive success of J. multidenatata could be seriously affected.

Meshkini et al., 2018

Meshkini, S., Rahimi-Arnaei, M., & Tafi, A. A.; “The acute and chronic effect of Roundup herbicide on histopathology and enzymatic antioxidant system of Oncorhynchus mykiss;” International Journal of Environmental Science and Technology, 2018; DOI: 10.1007/s13762-018-2095-y.

ABSTRACT:

Unconventional and uncontrolled use of agricultural pesticides and their influence in aquatic ecosystems during drainage process causes the accumulation of these toxins in body tissues of fish, and finally, it endangers human health. In order to determine the amount of pollution of Roundup pesticide in aquatics, acute and chronic effects of this poison on gill, kidney, and liver tissues and biochemical activities of cerebral acetyl cholinesterase and liver catalase in rainbow trout (Oncorhynchus mykiss) were investigated. To determine LC50 of Roundup pesticide in rainbow trout, acute doses of Roundup were introduced to fish tanks and fish mortality was recorded for 96 h, and Roundup LC50 was determined using SPSS Probit test. Chronic doses were determined based on the obtained LC50, and the effects of these concentrations were assessed on gill, kidney and liver tissues and cerebral acetyl cholinesterase and liver catalase activities over 28 days. Based on histopathology results, the following changes were observed: adhesion of secondary lamellae, bending of secondary lamellae in gill tissue, glomerular wrinkling, dilatation of Bowman’s capsule space in kidney tissue and necrosis, cellular swelling, and lipid degeneration in liver tissue. Cerebral acetyl cholinesterase and liver catalase activities significantly reduced in groups exposed to Roundup herbicide compared to the control group (p < 0.05). Generally, chronic concentrations of Roundup herbicide cause undesirable tissue and enzymatic changes in antioxidant system of rainbow trout. Therefore, assessment of biochemical factors and histopathological studies can be used as biomarkers in tracing the effects of agricultural toxins on aquatic habitat.

Ren et al., 2019

Ren, X., Dai, P., Perveen, A., Tang, Q., Zhao, L., Jia, X., Li, Y., & Li, C.; “Effects of chronic glyphosate exposure to pregnant mice on hepatic lipid metabolism in offspring;” Environmental Pollution, 2019, 254(Pt A), 112906; DOI: 10.1016/j.envpol.2019.07.074.

ABSTRACT:

Glyphosate is the active ingredient in Roundup, one of the most popular herbicides in the world, and its toxicity has caused increasing concerns. The present study aims to investigate the toxic effects of prenatal exposure to pure glyphosate or Roundup on lipid metabolism in offspring. During gestational days (GDs), ICR mice (from Institute of Cancer Research) were given distilled water, 0.5% glyphosate solution (w/v, 0.5 g/100 ml) or 0.5%-glyphosate Roundup solution orally. The livers and serum samples of the offspring were collected on gestational day 19 (GD19), postnatal day 7 (PND7) and PND21. The results showed a significant decrease in the body weight and obvious hepatic steatosis with excessive lipid droplet formation in offspring. Moreover, the concentrations of lipids such as triglycerides (TGs), total cholesterol (T-CHO), and low-density lipoprotein cholesterols (LDL-C) increased to a significant extent in both the serum and livers. Furthermore, there were significant differences in the expression levels of the genes SREBP1C, SREBP2, Fasn, Hmgcr, Hmgcs and PPARa, which are related to lipid biosynthesis or catabolism in the liver. These results demonstrate that chronic prenatal exposure to glyphosate can result in lipid metabolism disruption in the offspring of mice, as glyphosate exerts a negative influence on the expression of lipogenesis genes. FULL TEXT

Owagboriaye et al., 2019

Owagboriaye, F., Dedeke, G., Ademolu, K., Olujimi, O., Aladesida, A., & Adeleke, M., “Comparative studies on endogenic stress hormones, antioxidant, biochemical and hematological status of metabolic disturbance in albino rat exposed to roundup herbicide and its active ingredient glyphosate,” Environmental Science and Pollution Research International, 2019. DOI: 10.1007/s11356-019-04759-1.

ABSTRACT:

There have been growing concerns and uncertainty about reports attributing the metabolic disturbance induced by a commercial formulation of glyphosate-based herbicide to its active ingredient. We therefore compared the effects of Roundup Original(R) and its active ingredient glyphosate on some hypothalamic-pituitary-adrenal (HPA) hormones and oxidative stress markers, biochemical and hematological profiles in 56 adult male albino rats randomly assigned to seven treatments of eight rats per treatment. The rats were orally exposed to Roundup Original(R) and its active ingredient daily at 3.6 mg/kg body weight (bw), 50.4 and 248.4 mg/kgbw of glyphosate equivalent concentrations for 12 weeks, while control treatment received distilled water. Serum concentrations of corticosterone, adrenocorticotropic hormone, aldosterone and concentration of oxidative stress marker, biochemical and hematological profiles in the blood were determined. Concentrations of corticosterone and aldosterone were significantly higher (p < 0.05) in rats treated with Roundup in a dose-dependent manner. Reduced glutathione concentration, catalase, and butyrylcholinesterase activities reduced significantly in rats treated with Roundup relative to those treated with the active ingredient. Lipid peroxidation was observed in rats treated with Roundup. Biochemical and hematological profiles of rats treated with Roundup were significantly altered (p < 0.05). However, significant changes in only acid phosphatase, lactase dehydrogenase, bilirubin, and white blood cells in rats treated with the active ingredient at 50.4 mg/kg were observed. The severe metabolic disturbance and stress observed in rats treated with the commercial formulation of Roundup herbicide may not be associated with the mild changes induced by the active ingredient.

Jasper et al., 2012

Jasper, R., Locatelli, G. O., Pilati, C., & Locatelli, C., “Evaluation of biochemical, hematological and oxidative parameters in mice exposed to the herbicide glyphosate-Roundup(®),” Interdisciplinary Toxicology, 2012, 5(3), 133-140. DOI: 10.2478/v10102-012-0022-5.

ABSTRACT:

We evaluated the toxicity of hepatic, hematological, and oxidative effects of glyphosate-Roundup® on male and female albino Swiss mice. The animals were treated orally with either 50 or 500 mg/kg body weight of the herbicide, on a daily basis for a period of 15 days. Distilled water was used as control treatment. Samples of blood and hepatic tissue were collected at the end of the treatment. Hepatotoxicity was monitored by quantitative analysis of the serum enzymes ALT, AST, and γ-GT and renal toxicity by urea and creatinine. We also investigated liver tissues histopathologically. Alterations of hematological parameters were monitored by RBC, WBC, hemoglobin, hematocrit, MCV, MCH, and MCHC. TBARS (thiobarbituric acid reactive substances) and NPSH (non-protein thiols) were analyzed in the liver to assess oxidative damage. Significant increases in the levels of hepatic enzymes (ALT, AST, and γ-GT) were observed for both herbicide treatments, but no considerable differences were found by histological analysis. The hematological parameters showed significant alterations (500 mg/kg body weight) with reductions of RBC, hematocrit, and hemoglobin, together with a significant increase of MCV, in both sexes of mice. In males, there was an important increase in lipid peroxidation at both dosage levels, together with an NPSH decrease in the hepatic tissue, whereas in females significant changes in these parameters were observed only at the higher dose rate. The results of this study indicate that glyphosate-Roundup® can promote hematological and hepatic alterations, even at subacute exposure, which could be related to the induction of reactive oxygen species. FULL TEXT

Milic et al., 2018

Milic, Mirta, Zunec, Suzana, Micek, Vedran, Kasuba, Vilena, Mikolic, Anja, Lovakovic, Blanka Tariba, Semren, Tanja Zivkovic, Pavicic, Ivan, Cermak, Ana Marija Marjanovic, Pizent, Alica, Vrdoljak, Ana Lucic, Valencia-Quintana, Rafael, Sanchez-Alarcon, Juana, & Zeljezic, Davor, “Oxidative stress, cholinesterase activity, and DNA damage in the liver, whole blood, and plasma of Wistar rats following a 28-day exposure to glyphosate,” Archives of Industrial Hygiene and Toxicology, 2018, 69(2), 154-168. DOI: 10.2478/aiht-2018-69-3114.

ABSTRACT:

In this 28 day-study, we evaluated the effects of herbicide glyphosate administered by gavage to Wistar rats at daily doses equivalent to 0.1 of the acceptable operator exposure level (AOEL), 0.5 of the consumer acceptable daily intake (ADI), 1.75 (corresponding to the chronic population-adjusted dose, cPAD), and 10 mg kg-1 body weight (bw) (corresponding to 100 times the AOEL). At the end of each treatment, the body and liver weights were measured and compared with their baseline values. DNA damage in leukocytes and liver tissue was estimated with the alkaline comet assay. Oxidative stress was evaluated using a battery of endpoints to establish lipid peroxidation via thiobarbituric reactive substances (TBARS) level, level of reactive oxygen species (ROS), glutathione (GSH) level, and the activity of glutathione peroxidase (GSH-Px). Total cholinesterase activity and the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were also measured. The exposed animals gained less weight than control. Treatment resulted in significantly higher primary DNA damage in the liver cells and leukocytes. Glyphosate exposure significantly lowered TBARS in the liver of the AOEL, ADI, and cPAD groups, and in plasma in the AOEL and cPAD group. AChE was inhibited with all treatments, but the AOEL and ADI groups significantly differed from control. Total ChE and plasma/liver ROS/GSH levels did not significantly differ from control, except for the 35 % decrease in ChE in the AOEL and ADI groups and a significant drop in liver GSH in the cPAD and 100xAOEL groups. AOEL and ADI blood GSH-Px activity dropped significantly, but in the liver it significantly increased in the ADI, cPAD, and 100xAOEL groups vs. control. All these findings show that even exposure to low glyphosate levels can have serious adverse effects and points to a need to change the approach to risk assessment of low-level chronic/sub-chronic glyphosate exposure, where oxidative stress is not necessarily related to the genetic damage and AChE inhibition. FULL TEXT

de Souza et al., 2017

de Souza, Janaina Sena, Kizys, Marina Malta Letro, da Conceicao, Rodrigo Rodrigues, Glebocki, Gabriel, Romano, Renata Marino, Ortiga-Carvalho, Tania Maria, Giannocco, Gisele, da Silva, Ismael Dale Cotrim Guerreiro, Dias da Silva, Magnus Regios, Romano, Marco Aurelio, & Chiamolera, Maria Izabel, “Perinatal exposure to glyphosate-based herbicide alters the thyrotrophic axis and causes thyroid hormone homeostasis imbalance in male rats,” Toxicology, 2017, 377, 25-37. DOI: 10.1016/j.tox.2016.11.005.

ABSTRACT:

Glyphosate-based herbicides (GBHs) are widely used in agriculture. Recently, several animal and epidemiological studies have been conducted to understand the effects of these chemicals as an endocrine disruptor for the gonadal system. The aim of the present study was to determine whether GBHs could also disrupt the hypothalamic-pituitary-thyroid (HPT) axis. Female pregnant Wistar rats were exposed to a solution containing GBH Roundup((R))Transorb (Monsanto). The animals were divided into three groups (control, 5mg/kg/day or 50mg/kg/day) and exposed from gestation day 18 (GD18) to post-natal day 5 (PND5). Male offspring were euthanized at PND 90, and blood and tissues samples from the hypothalamus, pituitary, liver and heart were collected for hormonal evaluation (TSH-Thyroid stimulating hormone, T3-triiodothyronine and T4-thyroxine), metabolomic and mRNA analyses of genes related to thyroid hormone metabolism and function. The hormonal profiles showed decreased concentrations of TSH in the exposed groups, with no variation in the levels of the thyroid hormones (THs) T3 and T4 between the groups. Hypothalamus gene expression analysis of the exposed groups revealed a reduction in the expression of genes encoding deiodinases 2 (Dio2) and 3 (Dio3) and TH transporters Slco1c1 (former Oatp1c1) and Slc16a2 (former Mct8). In the pituitary, Dio2, thyroid hormone receptor genes (Thra1 and Thrb1), and Slc16a2 showed higher expression levels in the exposed groups than in the control group. Interestingly, Tshb gene expression did not show any difference in expression profile between the control and exposed groups. Liver Thra1 and Thrb1 showed increased mRNA expression in both GBH-exposed groups, and in the heart, Dio2, Mb, Myh6 (former Mhca) and Slc2a4 (former Glut4) showed higher mRNA expression in the exposed groups. Additionally, correlation analysis between gene expression and metabolomic data showed similar alterations as detected in hypothyroid rats. Perinatal exposure to GBH in male rats modified the HPT set point, with lower levels of TSH likely reflecting post-translational events. Several genes regulated by TH or involved in TH metabolism and transport presented varying degrees of gene expression alteration that were probably programmed during intrauterine exposure to GBHs and reflects in peripheral metabolism. In conclusion, the role of GBH exposure in HPT axis disruption should be considered in populations exposed to this herbicide. FULL TEXT

Lim et al., 2009

Soo Lim, Sun Young Ahn, In Chan Song, Myung Hee Chung, Hak Chul Jang, Kyong Soo Park, Ki-Up Lee, Youngmi Kim Pak , Hong Kyu Lee, “Chronic Exposure to the Herbicide, Atrazine, Causes Mitochondrial Dysfunction and Insulin Resistance,” PLOS One, 2009, 4:4, DOI: 10.1371/journal.pone.0005186

ABSTRACT:

There is an apparent overlap between areas in the USA where the herbicide, atrazine (ATZ), is heavily used and obesity-prevalence maps of people with a BMI over 30. Given that herbicides act on photosystem II of the thylakoid membrane of chloroplasts, which have a functional structure similar to mitochondria, we investigated whether chronic exposure to low concentrations of ATZ might cause obesity or insulin resistance by damaging mitochondrial function. Sprague-Dawley rats (n = 48) were treated for 5 months with low concentrations (30 or 300 µg kg−1 day−1) of ATZ provided in drinking water. One group of animals was fed a regular diet for the entire period, and another group of animals was fed a high-fat diet (40% fat) for 2 months after 3 months of regular diet. Various parameters of insulin resistance were measured. Morphology and functional activities of mitochondria were evaluated in tissues of ATZ-exposed animals and in isolated mitochondria. Chronic administration of ATZ decreased basal metabolic rate, and increased body weight, intra-abdominal fat and insulin resistance without changing food intake or physical activity level. A high-fat diet further exacerbated insulin resistance and obesity. Mitochondria in skeletal muscle and liver of ATZ-treated rats were swollen with disrupted cristae. ATZ blocked the activities of oxidative phosphorylation complexes I and III, resulting in decreased oxygen consumption. It also suppressed the insulin-mediated phosphorylation of Akt. These results suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a high-fat diet is prevalent. FULL TEXT

Mesnage et al., 2015b

Robin Mesnage, Matthew Arno, Manuela Costanzo, Manuela Malatesta, Gilles-Eric Séralini and Michael N. Antoniou, “Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure,” Environmental Health, 2015, 14:70, DOI 10.1186/s12940-015-0056-1.

ABSTRACT:

BACKGROUND:  Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH, such as Roundup, pose a particular health risk to liver and kidneys although low environmentally relevant doses have not been examined. To address this issue, a 2-year study in rats administering 0.1 ppb Roundup (50 ng/L glyphosate equivalent) via drinking water (giving a daily intake of 4 ng/kg bw/day of glyphosate) was conducted. A marked increased incidence of anatomorphological and blood/urine biochemical changes was indicative of liver and kidney structure and functional pathology. In order to confirm these findings we have conducted a transcriptome microarray analysis of the liver and kidneys from these same animals.

RESULTS: The expression of 4224 and 4447 transcript clusters (a group of probes corresponding to a known or putative gene) were found to be altered respectively in liver and kidney (p < 0.01, q < 0.08). Changes in gene expression varied from −3.5 to 3.7 fold in liver and from −4.3 to 5.3 in kidneys. Among the 1319 transcript clusters whose expression was altered in both tissues, ontological enrichment in 3 functional categories among 868 genes were found. First, genes involved in mRNA splicing and small nucleolar RNA were mostly upregulated, suggesting disruption of normal spliceosome activity. Electron microscopic analysis of hepatocytes confirmed nucleolar structural disruption. Second, genes controlling chromatin structure (especially histone-lysine N-methyltransferases) were mostly upregulated. Third, genes related to respiratory chain complex I and the tricarboxylic acid cycle were mostly downregulated. Pathway analysis suggests a modulation of the mTOR and phosphatidylinositol signalling pathways. Gene disturbances associated with the chronic administration of ultra-low dose Roundup reflect a liver and kidney lipotoxic condition and increased cellular growth that may be linked with regeneration in response to toxic effects causing damage to tissues. Observed alterations in gene expression were consistent with fibrosis, necrosis, phospholipidosis, mitochondrial membrane dysfunction and ischemia, which correlate with and thus confirm observations of pathology made at an anatomical, histological and biochemical level.

CONCLUSION: Our results suggest that chronic exposure to a GBH in an established laboratory animal toxicity model system at an ultra-low, environmental dose can result in liver and kidney damage with potential significant health implications for animal and human populations.  FULL TEXT

Krüger et al., 2014

Monika Krüger, Philipp Schledorn, Wieland Schrödl, Hans-Wolfgang Hoppe, Walburga Lutz, and Awad A. Shehata, “Detection of Glyphosate Residues in Animals and Humans,” Journal of Environmental and Analytical Toxicology, 2014, 4:2, DOI: 10.4172/2161-0525.1000210.

ABSTRACT:

In the present study glyphosate residues were tested in urine and different organs of dairy cows as well as in urine of hares, rabbits and humans using ELISA and Gas Chromatography-Mass Spectroscopy (GC-MS). The correlation coefficients between ELISA and GC-MS were 0.96, 0.87, 0.97and 0.96 for cattle, human, and rabbit urine and organs, respectively. The recovery rate of glyphosate in spiked meat using ELISA was 91%. Glyphosate excretion in German
dairy cows was significantly lower than Danish cows. Cows kept in genetically modified free area had significantly lower glyphosate concentrations in urine than conventional husbandry cows. Also glyphosate was detected in different organs of slaughtered cows as intestine, liver, muscles, spleen and kidney. Fattening rabbits showed significantly higher glyphosate residues in urine than hares. Moreover, glyphosate was significantly higher in urine of humans with
conventional feeding. Furthermore, chronically ill humans showed significantly higher glyphosate residues in urine than healthy population. The presence of glyphosate residues in both humans and animals could haul the entire population towards numerous health hazards, studying the impact of glyphosate residues on health is warranted and the global regulations for the use of glyphosate may have to be re-evaluated.  FULL TEXT

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