Bibliography Tag: liver damage

Baharuddin et al., 2011

Baharuddin, M. R., Sahid, I. B., Noor, M. A., Sulaiman, N., & Othman, F.; “Pesticide risk assessment: A study on inhalation and dermal exposure to 2,4-D and paraquat among Malaysian paddy farmers;” Journal of Environmental Science and Health, Part B, 2011, 46(7), 600-607; DOI: 10.1080/03601234.2011.589309.


A cross-section analytical study was conducted to evaluate the risk of pesticide exposure to those applying the Class II pesticides 2,4-D and paraquat in the paddy-growing areas of Kerian, Perak, Malaysia. It investigated the influence of weather on exposure as well as documented health problems commonly related to pesticide exposure. Potential inhalation and dermal exposure for 140 paddy farmers (handlers of pesticides) were assessed. Results showed that while temperature and humidity affected exposure, windspeed had the strongest impact on pesticide exposure via inhalation. However, the degree of exposure to both herbicides via inhalation was below the permissible exposure limits set by United States National Institute of Occupational Safety and Health (NIOSH). Dermal Exposure Assessment Method (DREAM) readings showed that dermal exposure with manual spraying ranged from moderate to high. With motorized sprayers, however, the level of dermal exposure ranged from low to moderate. Dermal exposure was significantly negatively correlated with the usage of protective clothing. Various types of deleterious health effects were detected among users of manual knapsack sprayers. Long-term spraying activities were positively correlated with increasing levels of the gamma-glutamyl transpeptidase (GGT) liver enzyme. The type of spraying equipment, usage of proper protective clothing and adherence to correct spraying practices were found to be the most important factors influencing the degree of pesticide exposure among those applying pesticides.

Mesnage et al., 2021D

Robin Mesnage, Mariam Ibragim, Daniele Mandrioli, Laura Falcioni, Eva Tibaldi, Fiorella Belpoggi, Inger Brandsma, Emma Bourne, Emanuel Savage, Charles A Mein, Michael N Antoniou; “Comparative Toxicogenomics of Glyphosate and Roundup Herbicides by Mammalian Stem Cell-Based Genotoxicity Assays and Molecular Profiling in Sprague-Dawley Rats”, Toxicological Sciences, 2021; DOI: 10.1093/toxsci/kfab143.


Whether glyphosate-based herbicides (GBHs) are more potent than glyphosate alone at activating cellular mechanisms, which drive carcinogenesis remain controversial. As GBHs are more cytotoxic than glyphosate, we reasoned they may also be more capable of activating carcinogenic pathways. We tested this hypothesis by comparing the effects of glyphosate with Roundup GBHs both in vitro and in vivo. First, glyphosate was compared with representative GBHs, namely MON 52276 (European Union), MON 76473 (United Kingdom), and MON 76207 (United States) using the mammalian stem cell-based ToxTracker system. Here, MON 52276 and MON 76473, but not glyphosate and MON 76207, activated oxidative stress and unfolded protein responses. Second, molecular profiling of liver was performed in female Sprague-Dawley rats exposed to glyphosate or MON 52276 (at 0.5, 50, and 175 mg/kg bw/day glyphosate) for 90 days. MON 52276 but not glyphosate increased hepatic steatosis and necrosis. MON 52276 and glyphosate altered the expression of genes in liver reflecting TP53 activation by DNA damage and circadian rhythm regulation. Genes most affected in liver were similarly altered in kidneys. Small RNA profiling in liver showed decreased amounts of miR-22 and miR-17 from MON 52276 ingestion. Glyphosate decreased miR-30, whereas miR-10 levels were increased. DNA methylation profiling of liver revealed 5727 and 4496 differentially methylated CpG sites between the control and glyphosate and MON 52276 exposed animals, respectively. Apurinic/apyrimidinic DNA damage formation in liver was increased with glyphosate exposure. Altogether, our results show that Roundup formulations cause more biological changes linked with carcinogenesis than glyphosate. FULL TEXT

Ndonwi et al., 2019

Ndonwi EN, Atogho-Tiedeu B, Lontchi-Yimagou E, Shinkafi TS, Nanfa D, Balti EV, Indusmita R, Mahmood A, Katte JC, Mbanya A, Matsha T, Mbanya JC, Shakir A, Sobngwi E. “Gestational Exposure to Pesticides Induces Oxidative Stress and Lipid Peroxidation in Offspring that Persist at Adult Age in an Animal Model.” Toxicological Research, 2019 Jul;35(3):241-248; DOI: 10.5487/TR.2019.35.3.241.


Pesticide exposure may induce biochemical alterations including oxidative stress and lipid peroxidation. However, in the context of developmental origin of health and disease, putative trans-generational effect of exposure to pesticides are insufficiently studied. We therefore aimed to evaluate the biochemical effect of gestational exposure to four pesticides on female Wistar rats and their offspring at adult age. We studied 30 female nulliparous Wistar rats divided into 5 equal groups. Group 1 served as the control group and received distilled water while group 2, 3, 4 and 5 received orally pesticide 1 (imidacloprid), pesticide 2 (chlorpyrifos), pesticide 3 (imidacloprid + lambda cyhalothrin) and pesticide 4 (oxamyl) respectively once daily throughout gestation at a dose equivalent to 1/10 lethal dose 50. The mothers were followed up until one month post gestation. The offspring were followed up from birth until adult age (12 weeks). In all animals at each time point we evaluated malondialdehyde (MDA), oxidative stress and liver function enzymes. There was similar variation of total body weight in all the groups during and after gestation. However, Female Wistar rats of the exposed groups had significant alterations in liver SOD (-30.8% to +64.1%), catalase (-38.8% to -85.7%) and GSH (-29.2% to -86.5%) and; kidney catalase (> 100%), GSH (> 100%). Moreover, MDA, alanine transaminase (ALT) and aspartate transaminase (AST) levels were significantly higher in pesticide exposed rats compared to the control group. Similar alterations in antioxidant enzymes, MDA and liver function enzymes were observed in offspring of treated rats evidenced at weaning and persisting until adult age. Exposure to pesticides causes oxidative stress and lipid peroxidation in exposed female Wistar rats and their offspring. The persistence in offspring at adult age suggests transgenerational adverse effects. FULL TEXT

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