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<p>Environmental contamination with heavy metals increases the risk of copper (Cu<sup>2</sup>⁺) exposure in fish, animals, and humans, potentially leading to poisoning and even fatality. This study aimed to assess the alleviating effects of α-lipoic acid (α-LA), a potent antioxidant, on oxidative stress and lipid metabolism disorders elicited by Cu<sup>2</sup>⁺. Swamp eel (<i>Monopterus albus</i>) were randomly divided into four groups: control group (untreated), α-LA group (+ α-LA 1000&#xa0;mg/kg), Cu<sup>2</sup>⁺ group (+ Cu<sup>2</sup>⁺ 500&#xa0;mg/kg), and Cu<sup>2</sup>⁺ + α-LA (+ Cu<sup>2</sup>⁺ 500&#xa0;mg/kg + α-LA 1000&#xa0;mg/kg) group, and were fed for 56&#xa0;days. Subsequently, the effects of α-LA on Cu<sup>2</sup>⁺-induced toxicity were investigated by analyzing histopathological alterations, biochemical indicators and gene expression profile alterations. Our findings demonstrated that α-LA administration significantly diminishes hepatic Cu<sup>2</sup>⁺ accumulation and mitigates hepatic histopathological lesions caused by Cu<sup>2</sup>⁺. Moreover, α-LA invigorated the potency of antioxidant enzymes, including POD, GPx, and GST, and diminished GSSG levels. Besides, α-LA alleviated Cu<sup>2</sup>⁺-induced oxidative stress via the Nrf2 signaling pathway by its fine-tuning towards various genes (up-regulation of <i>nrf2</i>, <i>cat</i>, and <i>gclc</i>, and down-regulation of <i>ho-1</i>, <i>sod1</i>, and <i>nqo1</i>). Meanwhile, α-LA also alleviated dyslipidemia by reducing Cu<sup>2</sup>⁺-induced steatosis and lowering serum levels of T-CHO, LDL-CHO, and TG, while increasing HDL-CHO and LPL + HL. Furthermore, α-LA relieved Cu<sup>2</sup>⁺-induced lipid metabolic disorders induced by upregulating the expression levels of genes related to the PPARα signaling pathway, encompassing <i>pparα-like</i>, <i>rxrα</i>, <i>lpl-like</i>, <i>acsl4a</i>, <i>acox1</i>, and <i>me1,</i> and promoted lipolysis and decreased lipid accumulation. In summary, α-LA possesses protective effects against Cu<sup>2</sup>⁺-induced oxidative stress and lipid metabolism disorders by activating the Nrf2/PPARα signaling pathway in swamp eel. This study provides insights into alleviating the toxicity of heavy metals in aquatic organisms.</p>

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Alleviating effect of α-lipoic acid on copper-induced oxidative stress and lipid metabolism disorders in swamp eel (Monopterus albus)

  • 期刊论文

  • 发表日期：

    2025年11月19日

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  • Miao He,
  • Chuanqi Yu,
  • Jianping Fu,
  • Ximei Liang,
  • Hui Wang,
  • Chenhao Niu,
  • Kexin Xiong,
  • Lili Wei

摘要

Environmental contamination with heavy metals increases the risk of copper (Cu2⁺) exposure in fish, animals, and humans, potentially leading to poisoning and even fatality. This study aimed to assess the alleviating effects of α-lipoic acid (α-LA), a potent antioxidant, on oxidative stress and lipid metabolism disorders elicited by Cu2⁺. Swamp eel (Monopterus albus) were randomly divided into four groups: control group (untreated), α-LA group (+ α-LA 1000 mg/kg), Cu2⁺ group (+ Cu2⁺ 500 mg/kg), and Cu2⁺ + α-LA (+ Cu2⁺ 500 mg/kg + α-LA 1000 mg/kg) group, and were fed for 56 days. Subsequently, the effects of α-LA on Cu2⁺-induced toxicity were investigated by analyzing histopathological alterations, biochemical indicators and gene expression profile alterations. Our findings demonstrated that α-LA administration significantly diminishes hepatic Cu2⁺ accumulation and mitigates hepatic histopathological lesions caused by Cu2⁺. Moreover, α-LA invigorated the potency of antioxidant enzymes, including POD, GPx, and GST, and diminished GSSG levels. Besides, α-LA alleviated Cu2⁺-induced oxidative stress via the Nrf2 signaling pathway by its fine-tuning towards various genes (up-regulation of nrf2, cat, and gclc, and down-regulation of ho-1, sod1, and nqo1). Meanwhile, α-LA also alleviated dyslipidemia by reducing Cu2⁺-induced steatosis and lowering serum levels of T-CHO, LDL-CHO, and TG, while increasing HDL-CHO and LPL + HL. Furthermore, α-LA relieved Cu2⁺-induced lipid metabolic disorders induced by upregulating the expression levels of genes related to the PPARα signaling pathway, encompassing pparα-like, rxrα, lpl-like, acsl4a, acox1, and me1, and promoted lipolysis and decreased lipid accumulation. In summary, α-LA possesses protective effects against Cu2⁺-induced oxidative stress and lipid metabolism disorders by activating the Nrf2/PPARα signaling pathway in swamp eel. This study provides insights into alleviating the toxicity of heavy metals in aquatic organisms.