Bibliography Tag: liver damage

Tang et al., 2021

Tang, J., Wang, W., Jiang, Y., & Chu, W.; “Diazinon exposure produces histological damage, oxidative stress, immune disorders and gut microbiota dysbiosis in crucian carp (Carassius auratus gibelio);” Environmental Pollution, 2021, 269, 116129; DOI: 10.1016/j.envpol.2020.116129.


Diazinon is a common organophosphate pesticide widely used to control parasitic infections in agriculture. Excessive use of diazinon can have adverse effects on the environment and aquatic animal health. In the present study, the toxic effects of diazinon on the histology, antioxidant, innate immune and intestinal microbiota community composition of crucian carp (Carassius auratus gibelio) were investigated. The results showed that diazinon at the tested concentration (300 mug/L) induced gill and liver histopathological damages. Hepatic total superoxide dismutase (T-SOD), catalase (CAT), and glutathione S-transferase (GST) activities significantly decreased (P < 0.05) by 32.47%, 65.33% and 37.34%, respectively. However, the liver tissue malondialdehyde (MDA) content significantly (P < 0.05) increased by 138.83%. The 300 mug/L diazinon significantly (P < 0.05) downregulated the gene expression of TLR4, MyD88, NF-kB p100 and IL-8 but had no significant effect TNF-alpha (P = 0.8239). In addition, the results demonstrated that diazinon exposure could affect the intestinal microbiota composition and diversity. Taken together, the results of this study indicated that diazinon exposure can cause damage to crucian carp, induce histopathological damage in gill and liver tissues, oxidative stress in the liver, and innate immune disorders and alter intestinal microbiota composition and diversity.

Hernandez et al., 2006

Hernandez, A. F., Amparo Gomez, M., Perez, V., Garcia-Lario, J. V., Pena, G., Gil, F., Lopez, O., Rodrigo, L., Pino, G., & Pla, A.; “Influence of exposure to pesticides on serum components and enzyme activities of cytotoxicity among intensive agriculture farmers;” Environmental Research, 2006, 102(1), 70-76; DOI: 10.1016/j.envres.2006.03.002.


Although the effects of acute pesticide poisoning are well known for the pesticides most currently used, hardly any data exist on health effects after long-term low-dose exposures. Major unresolved issues include the effect of moderate exposure in the absence of poisoning. The increased utilization of pesticides other than organophosphates makes it even more difficult to find associations. In this study a cohort of 106 intensive agriculture workers were assessed twice during the course of a spraying season for changes in serum biochemistry, namely enzymes reflecting cytotoxicity (AST, ALT, LDH, CK, and amino-oxidase) and other biochemical parameters, such as markers of nephrotoxicity (urea, creatinine) and lipid profile (cholesterol and triglycerides). Several criteria for estimating pesticide exposure were used, the most important one being serum cholinesterase depression greater than 25% from baseline to peak exposure. Our results revealed an association of pesticide exposure with changes in AST (increased activity), LDH, and amino-oxidase (decreased activity) as well as with changes in serum creatinine and phosphorus (lower and higher levels, respectively). These results provide support for a very slight impairment of the liver function, but overall these findings are consistent with no clinically significant hepatotoxicity. Intriguingly, paraoxonase-1 R allele was found to be an independent predictor of higher rates of AST and lower rates of amino-oxidase, so that it may play a supporting role as an individual marker of susceptibility on pesticide-induced health effects. In conclusion, different biomarkers might be used to detect early biochemical effects of pesticides before adverse clinical health effects occur. FULL TEXT

Pandey et al., 2019

Pandey, A., Dhabade, P., & Kumarasamy, A.; “Inflammatory Effects of Subacute Exposure of Roundup in Rat Liver and Adipose Tissue;” Dose Response, 2019, 17(2), 1559325819843380; DOI: 10.1177/1559325819843380.


Roundup is a popular herbicide containing glyphosate as an active ingredient. The formulation of Roundup is speculated to have critical toxic effects, one among which is chronic inflammation. The present study analyzed adverse inflammatory effects in the liver and adipose tissue of rats after a subacute exposure of Roundup. Adult male rats were exposed to various doses of Roundup (0, 5, 10, 25, 50, 100 and 250 mg/kg bodyweight [bw] glyphosate) orally, everyday for 14 days. On day 15, liver and adipose tissues from dosed rats were analyzed for inflammation markers. C-reactive protein in liver, cytokines IL-1beta, TNF-alpha, IL-6, and inflammatory response marker, and prostaglandin-endoperoxide synthase were upregulated in liver and adipose of rats exposed to higher (100 and 250 mg/kg bw/d) doses of Roundup. Cumulatively, our data suggest development of inflammation in lipid and hepatic organs upon exposure to Roundup. Furthermore, liver histological studies showed formation of vacuoles, fibroid tissue, and glycogen depletion in the groups treated with doses of higher Roundup. These observations suggest progression of fatty liver disease in Roundup-treated adult rats. In summary, our data suggest progression of multiorgan inflammation, liver scarring, and dysfunction post short-term exposure of Roundup in adult male rats.  FULL TEXT

Mills et al., 2019

Mills, P. J., Caussy, C., & Loomba, R.; “Glyphosate Excretion is Associated With Steatohepatitis and Advanced Liver Fibrosis in Patients With Fatty Liver Disease;” Clinical Gastroenterology and Hepatology, 2019; DOI: 10.1016/j.cgh.2019.03.045.


Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in developed countries.(1) Patients with nonalcoholic steatohepatitis (NASH) are considered to be at a higher risk of fibrosis progression and development to cirrhosis and hepatocellular carcinoma.

Among potential environmental contributors to the pathophysiology of NAFLD are exposure to pesticides and herbicides. Glyphosate, the primary weed-killing ingredient in Roundup (Monsanto, St Louis, MO), is sprayed on genetically modified crops and on many non–genetically modified grain crops and is found in these crops at harvest.

Rodents chronically fed with a low dosage of glyphosate exhibit signs of hepatotoxicity, liver congestion, necrosis, and DNA damage of the liver cells. This study examined excretion levels of glyphosate and its primary metabolite aminomethylphosphonic acid (AMPA) in a well-characterized and prospectively recruited cohort of patients with biopsy-proven NAFLD. FULL TEXT

Beuret et al., 2005

Beuret, Cecilia Judith, Zirulnik, Fanny, & Giménez, María Sofía; “Effect of the herbicide glyphosate on liver lipoperoxidation in pregnant rats and their fetuses;” Reproductive Toxicology, 2005, 19(4), 501-504; DOI: 10.1016/j.reprotox.2004.09.009.


Glyphosate is a post-emergence herbicide that acts on the synthesis of amino acids and other endogenous metabolites in plants. It is commonly used in agriculture, forestry, and nurseries for the control or destruction of herbaceous plants. Metabolic processes during development and pregnancy could be sensitive to changes induced by glyphosate such as lipid peroxidation. The present study has investigated the effects that 1% glyphosate oral exposure has on lipoperoxidation and antioxidant enzyme systems in the maternal serum and liver of pregnant rats and their term fetuses at 21 days of gestation. The results suggest that excessive lipid peroxidation induced with glyphosate ingestion leads to an overload of maternal and fetal antioxidant defense systems.

El-Shenawy, 2009

El-Shenawy, Nahla S.; “Oxidative stress responses of rats exposed to Roundup and its active ingredient glyphosate;” Environmental Toxicology and Pharmacology, 2009, 28(3), 379-385; DOI: 10.1016/j.etap.2009.06.001.

Glyphosate is the active ingredient and polyoxyethyleneamine, the major component, is the surfactant present in the herbicide Roundup formulation. The objective of this study was to analyze potential cytotoxicity of the Roundup and its fundamental substance (glyphosate). Albino male rats were intraperitoneally treated with sub-lethal concentration of Roundup (269.9mg/kg) or glyphosate (134.95mg/kg) each 2 days, during 2 weeks. Hepatotoxicity was monitored by quantitative analysis of the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities, total protein, albumin, triglyceride and cholesterol. Creatinine and urea were used as the biochemical markers of kidney damages. The second aim of this study to investigate how glyphosate alone or included in herbicide Roundup affected hepatic reduced glutathione (GSH) and lipid peroxidation (LPO) levels of animals as an index of antioxidant status and oxidative stress, respectively, as well as the serum nitric oxide (NO) and alpha tumour necrosis factor (TNF-α) were measured. Treatment of animals with Roundup induced the leakage of hepatic intracellular enzymes, ALT, AST and ALP suggesting irreversible damage in hepatocytes starting from the first week. It was found that the effects were different on the enzymes in Roundup and glyphosate-treated groups. Significant time-dependent depletion of GSH levels and induction of oxidative stress in liver by the elevated levels of LPO, further confirmed the potential of Roundup to induce oxidative stress in hepatic tissue. However, glyphosate caused significant increases in NO levels more than Roundup after 2 weeks of treatment. Both treatments increased the level of TNF-α by the same manner. The results suggest that excessive antioxidant disruptor and oxidative stress is induced with Roundup than glyphosate.

Ford et al., 2017

Ford, B., Bateman, L. A., Gutierrez-Palominos, L., Park, R., & Nomura, D. K.; “Mapping Proteome-wide Targets of Glyphosate in Mice;” Cell Chemical Biology, 2017, 24(2), 133-140; DOI: 10.1016/j.chembiol.2016.12.013.


Glyphosate, the active ingredient in the herbicide Roundup, is one of the most widely used pesticides in agriculture and home garden use. Whether glyphosate causes any mammalian toxicity remains highly controversial. While many studies have associated glyphosate with numerous adverse health effects, the mechanisms underlying glyphosate toxicity in mammals remain poorly understood. Here, we used activity-based protein profiling to map glyphosate targets in mice. We show that glyphosate at high doses can be metabolized in vivo to reactive metabolites such as glyoxylate and react with cysteines across many proteins in mouse liver. We show that glyoxylate inhibits liver fatty acid oxidation enzymes and glyphosate treatment in mice increases the levels of triglycerides and cholesteryl esters, likely resulting from diversion of fatty acids away from oxidation and toward other lipid pathways. Our study highlights the utility of using chemoproteomics to identify novel toxicological mechanisms of environmental chemicals such as glyphosate. FULL TEXT

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.


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.


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.


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