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<p>Cadmium (Cd) is a major public health concern. In this study, we investigated whether grape seed extract (GSE) can mitigate the liver damage induced by Cd exposure. Male Wistar rats were administered daily treatments for 14&#xa0;days consisting of either Cd (1&#xa0;mg/kg) or GSE (50&#xa0;mg/kg) and Cd (1&#xa0;mg/kg), then sacrificed and their plasma and liver collected for biochemical and molecular analyses. Cd provoked liver injury as assessed by increased activity of alanine aminotransferase (ALAT) by 78%, aspartate aminotransferase (ASAT) by 72%, and lactate dehydrogenase (LDH) by 81%. Cd also induced the deregulation of essential metals level such as calcium (+ 195%), magnesium (+ 104%) and iron (–39%), and generated an oxidative stress characterized by increased protein carbonylation (PC) by 201%, lipid peroxidation (LPO) by 134%, hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) by 150% and xanthine oxidase (XO) activity by 256%, as well as decreased non-protein thiols (NPSH) by 52% and manganese superoxide dismutase (Mn-SOD), catalase (CAT) and glutathione peroxidase (GPx) activities (–65.2%, –48.3%, and –49.3%, respectively) and genes expression (–77.3%, –80.9%, and –73.3%, respectively). Cd also dropped mitochondrial viability by 42.9% and fueling enzymes activities such as α-ketoglutarate dehydrogenase (α-KGDH) by 47%, fumarase (FH) by 18%, and electron transport chain (ETC) complex I and II by 60% and 47%, respectively. Remarkably, GSE prevented all the harmful effects of Cd within the liver by means of stimulating the anti-oxidant system, and also through activating the metallothioneins (MTs) detoxification system. Thus, GSE appears as a safe and promising tool for the protection against non-essential heavy metals as Cd toxicity within the liver, and for the valorization of grape pomace to promote circular economy and environmental ecology concepts.</p> Graphical abstract <p></p>

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Protective effect of grape seed extract against cadmium-induced hepatotoxicity in rat

  • 期刊论文

  • 发表日期：

    2026年5月14日

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  • Wassim Ben Abbes,
  • Slim Ghrir,
  • Kamel Charradi,
  • Rym Essid,
  • Ghassen Abid,
  • Ferid Limam,
  • Ezzedine Aouani,
  • Salem Elkahoui

摘要

Cadmium (Cd) is a major public health concern. In this study, we investigated whether grape seed extract (GSE) can mitigate the liver damage induced by Cd exposure. Male Wistar rats were administered daily treatments for 14 days consisting of either Cd (1 mg/kg) or GSE (50 mg/kg) and Cd (1 mg/kg), then sacrificed and their plasma and liver collected for biochemical and molecular analyses. Cd provoked liver injury as assessed by increased activity of alanine aminotransferase (ALAT) by 78%, aspartate aminotransferase (ASAT) by 72%, and lactate dehydrogenase (LDH) by 81%. Cd also induced the deregulation of essential metals level such as calcium (+ 195%), magnesium (+ 104%) and iron (–39%), and generated an oxidative stress characterized by increased protein carbonylation (PC) by 201%, lipid peroxidation (LPO) by 134%, hydrogen peroxide (H2O2) by 150% and xanthine oxidase (XO) activity by 256%, as well as decreased non-protein thiols (NPSH) by 52% and manganese superoxide dismutase (Mn-SOD), catalase (CAT) and glutathione peroxidase (GPx) activities (–65.2%, –48.3%, and –49.3%, respectively) and genes expression (–77.3%, –80.9%, and –73.3%, respectively). Cd also dropped mitochondrial viability by 42.9% and fueling enzymes activities such as α-ketoglutarate dehydrogenase (α-KGDH) by 47%, fumarase (FH) by 18%, and electron transport chain (ETC) complex I and II by 60% and 47%, respectively. Remarkably, GSE prevented all the harmful effects of Cd within the liver by means of stimulating the anti-oxidant system, and also through activating the metallothioneins (MTs) detoxification system. Thus, GSE appears as a safe and promising tool for the protection against non-essential heavy metals as Cd toxicity within the liver, and for the valorization of grape pomace to promote circular economy and environmental ecology concepts.

Graphical abstract