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Chlorpyrifos (CPF) poisoning is a public health problem for which there is not currently any effective prophylaxis. In this study, we investigated the protective effect of grape seed extract (GSE) against CPF-induced hepatotoxicity. Rats were daily treated either with CPF (2 mg/kg) or CPF and GSE (20 mg/kg) for 1 week, sacrificed, and their livers dissected for biochemical, molecular, and histopathological analyses. CPF generated liver dysfunction by altering carbohydrate, lipid, amino acid, ammonia and urea metabolism, and provoked mitochondrial impairment through disturbing tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and mitochondrial viability. CPF also induced cholinergic excitotoxicity along with oxidative stress and histopathological alterations. Interestingly, treatment with GSE prevented all the detrimental effects of CPF through the regulation of cytochrome P450 (CYP450) gene expression. Molecular docking analysis indicated that GSE-containing polyphenols acted as epigenetic modulators through inhibiting DNA (cytosine-5)-methyltransferase 1 (DNMT1), thus favoring the CYP2C6 detoxification pathway. Thereby, GSE might be a promising strategy in the protection of the liver against CPF toxicity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aims of this study were to determine the polyphone content of grape seed extract (GSE) and to assess their protective effects against zearalenone (ZEN)-induced maternal toxicity and in utero development defects in mice. Five groups of pregnant mice were treated orally during days 6-13 of gestation as follows: control group, corn oil as vehicle (0.1 ml/mice)-treated group, ZEN-treated group (25 mg/kg b.w), GSE-treated group (150 mg/kg b.w.), and ZEN plus GSE-treated group. All animals were sacrificed on the 19th day of gestation and samples of bone marrow were collected for the micronucleus assay. The maternal and developmental toxicity were carried out. The HPLC analyses revealed that GES is rich in gallic acid, syringic acid, vanillin, quercetin, and coumaric acid. ZEN administration resulted in severe maternal and developmental toxicity which included an increase of micronuclei formation in bone marrow, decreased maternal weight gain, and litter weight. It also induces fetal growth retardation, increased number of the aborted dams and resorbed fetuses, abnormality of fetal bone ossification, and number of fetuses with a hematoma. GSE showed positive effects on the pregnant mice and the developing fetuses. Moreover, it counteracted the detrimental effects of ZEN in dams and fetuses. It could be concluded that polyphenols in GSE are a promising candidate to protect against ZEN toxicity in highly endemic areas.