Biology subjects

Tibaldi, E.

Publications and source records attributed to Tibaldi, E..

5 recordsLinked to original sources

bioRxiv2026

Cytotoxic Effects of Multiple Pesticides and their Mixtures on Caco-2 Cells Evaluated by Using MTT and Trypan Blue Assays

BACKGROUND: Pesticides are extensively used in agriculture, raising concerns about their potential impact on human health through dietary and environmental exposure. OBJECTIVES: This study evaluated the in vitro cytotoxicity of ten commonly used pesticides and their mixtures (lambda-cyhalothrin, cypermethrin, deltamethrin, tebuconazole, glyphosate, acetamiprid, cyprodinil, piperonyl butoxide, fluopyram, and imazalil) on human intestinal Caco-2 cells. METHODS: Cytotoxicity was assessed using the MTT assay, as a measure of metabolic activity, and the trypan blue exclusion test, as an indicator of cell membrane integrity. FINDINGS: Results showed that high concentrations (100 mg/L) of all pesticides significantly reduced cell viability and vitality. Notably, glyphosate and tebuconazole exhibited significant toxicity even at lower concentrations, respectively 0.1 mg/L and 10 mg/L. Combination treatments (Top 3 and Top 8 pesticide mixtures) retained the cytotoxic effects observed for individual compounds, showing additive (non-synergistic) effects. CONCLUSIONS: Overall, these findings indicate that certain pesticides-based herbicides can exert cytotoxic effects on intestinal cells even at relatively low concentrations and highlight the importance of using the component-based approach in mixture risk assessment for humans. This study was performed as part of the EU SPRINT (Sustainable Plant Protection Transition: A Global Health Approach) project.

pharmacology and toxicology↗

bioRxiv2026

Multiple Pesticides and their Mixtures Tested for Genotoxicity in the Micronucleus Assays on Intestinal Caco-2 Cells

Widespread exposure to multiple pesticides might potentially represent a genotoxic risk to humans. However the effects of these mixtures are largely unknown. Genotoxicity is a key characteristic of carcinogens, and its assessment represents an important component of the overall safety assessment of pesticides. In the present study, in vitro micronucleus test on intestinal Caco-2 human cells was performed according to OECD TG 487 in order to ascertain the genotoxicity of ten commonly used pesticides (dose range 0-100 mg L-1), tested as individual pesticides or mixtures. Significant dose-related increases in micronuclei were observed for exposures to lambda-cyhalothrin, tebuconazole, glyphosate, deltamethrin, fluopyram and the synergist piperonyl butoxide. Significant increases of micronuclei were also observed at different doses for cypermethrin, acetamiprid and cyprodinil, however these increases were not dose-dependent. Imazalil genotoxicity could not be analyzed due to confounding of high cytotoxicity even at low doses. Results show that the co-formulant piperonyl butoxide was genotoxic to human cell lines at all tested doses. Moreover, glyphosate, acetamiprid and fluopyram showed genotoxic effects at concentrations of 0.01-1.0 mg L-1. Although previously reported to be not genotoxic cyprodinil and deltamethrin were observed to be genotoxic to Caco-2 cells. A combination of 3 prioritzided pesticides (acetamiprid, glyphosate, tebuconazole) showed genotoxic effects even at the lowest dose. A combination of 8 prioritized pesticides showed genotoxicity at the highest dose. No synergistic interactions in micronuclei formation were evident in either the mixture of 3 or 8 prioritized pesticides. This study provides important information on the genotoxicity of different widely used pesticides and confirms the validity of a component-based approach in genotoxicity assessment of pesticide mixtures. This study was performed as part of the EU SPRINT (Sustainable Plant Protection Transition: A Global Health Approach) project.

pharmacology and toxicology↗

bioRxiv2025

Genome-scale multi-organ analysis of mutagenic effects of ethanol and acetaldehyde in Sprague Dawley rats

Alcohol consumption is a major cancer risk factor, particularly for head and neck cancers, including the oral cavity. Acetaldehyde, the primary genotoxic metabolite of ethanol, may play key roles in oral carcinogenesis, though the mechanisms remain unclear. While mutational signatures SBS16, DBS4, and ID11 have been tentatively linked to alcohol use, they are not exclusive to alcohol-related cancers. In this study, we examined the genome-wide in vivo mutagenic effects of ethanol and acetaldehyde by analyzing tumors from the cheek, Zymbal gland, larynx, forestomach, and liver of rats chronically exposed to these compounds. Signature analysis revealed exposure-specific, early-onset formation of SBS17 in [~]28% of head and neck tumors, suggesting inflammation and/or oxidative damage as potential mediators of carcinogenesis. Cancer driver gene analysis identified a relative enrichment of exposed tumors with mutations in the Tp53 and Mtor genes. No notable exposure-specific changes were observed in doublet-base substitutions, indel signatures, or copy number variants. Notably, SBS16, DBS4, and ID11 were absent. Our findings suggest direct mutagenicity may not be the main driver of alcohol-related cancer. Other harmful cellular effects, undetectable by whole genome sequencing, may be involved. Our findings suggest that SBS17 could function as a potential exposure-specific molecular marker of alcohol-related cancers in humans.

cancer biology↗

bioRxiv2023

Leukemia in Sprague-Dawley Rats Exposed Long-term from Prenatal Life to Glyphosate and Glyphosate-Based Herbicides

BackgroundGlyphosate-based herbicides (GBHs) are the worlds most widely used weed control agents. There has been intense and increasing public health concern about glyphosate and GBHs since the International Agency for Research on Cancer classified glyphosate as a probable human carcinogen in 2015. AimsTo further study the health effects of glyphosate and GBHs, the Ramazzini Institute, in collaboration with an international network of institutes and universities, has launched the Global Glyphosate Study (GGS), the most comprehensive toxicological study ever performed on these compounds. The GGS is an integrated study designed to test a wide range of toxicological outcomes including carcinogenicity, neurotoxicity, multi-generational effects, organ toxicity, endocrine disruption and prenatal developmental toxicity. The present study reports the first definitive results on leukemia incidence and mortality from the carcinogenicity arm of the GGS. MethodGlyphosate and two GBHs, Roundup Bioflow (MON 52276) used in the European Union (EU) and RangerPro (EPA 524-517) used in the U.S., were administered long-term to Sprague-Dawley (SD) rats beginning in prenatal life until 104 weeks of age via drinking water at doses of 0.5, 5, and 50 mg/kg body weight/day. This dose range encompasses both the EU Acceptable Daily Intake (ADI) and the EU No Observed Adverse Effect Level (NOAEL) for glyphosate. Each experimental group was composed of 51 males and 51 females, the total number animals were 1020 (510 males and 510 females). ResultsIn the animals exposed to glyphosate, a significantly increased trend in incidence of lymphoblastic leukemia was observed in males. In the Roundup Bioflow-treated animals, significantly increased trends were observed in incidence of lymphoblastic leukemia (males and females), monocytic leukemia (males), total myeloid leukemia (males), and all leukemias combined (males and females). In the RangerPro-treated animals, significantly increased trends were observed in incidence of lymphoblastic leukemia (males and females), monocytic leukemia (males) and all leukemias combined (males). 43% of leukemias deaths in the glyphosate and GBHs treated groups occurred before the first year of age (52 weeks). ConclusionsGlyphosate and GBHs at exposure levels corresponding to the EU ADI and the EU NOAEL caused significant, dose-related increased trends in incidence of leukemia, a very rare malignancy, in SD rats. Notably, about half of the leukemia deaths seen in the glyphosate and GBH groups occurred at less than one year of age, comparable to less than 35-40 years of age in humans.

pharmacology and toxicology↗

bioRxiv2021

TRAP1 and cyclophilin D compete at OSCP subunit to regulate enzymatic activity and permeability transition pore opening by F-ATP synthase

Binding of the mitochondrial chaperone TRAP1 to client proteins shapes cell bioenergetic and proteostatic adaptations, but the panel of TRAP1 clients is only partially defined. Here we show that TRAP1 interacts with F-ATP synthase, the protein complex that provides most cellular ATP. TRAP1 competes with the peptidyl-prolyl cis-trans isomerase cyclophilin D (CyPD) for binding to the oligomycin sensitivity-conferring protein (OSCP) subunit of F-ATP synthase, increasing its catalytic activity and counteracting the inhibitory effect of CyPD. Moreover, TRAP1 inhibits opening of the permeability transition pore (PTP) formed by F-ATP synthase and effectively antagonizes the PTP-inducing effect of CyPD, which elicits mitochondrial depolarization and cell death. Consistently, electrophysiological measurements indicate that TRAP1 and CyPD compete in the modulation of channel activity of purified F-ATP synthase, resulting in PTP inhibition and activation, respectively, and outcompeting each other effect on the channel. Moreover, TRAP1 counteracts PTP induction by CyPD, whereas CyPD reverses TRAP1-mediated PTP inhibition. Our data identify TRAP1 as a F-ATP synthase regulator that can influence cell bioenergetics and survival and can be targeted in pathological conditions where these processes are dysregulated, such as cancer.

cell biology↗