Ilyas Kainat, Rehman Kanwal, Iqbal Hajra, Hussain Amjad, Akash Muhammad Sajid Hamid, Shahid Mudassar, Sadaf Bushra
Department of Pharmaceutical Chemistry, Government College University, Faisalabad 38000, Pakistan.
Department of Pharmacy, The Women University, Multan 66000, Pakistan.
Bioengineering (Basel). 2024 Nov 13;11(11):1141. doi: 10.3390/bioengineering11111141.
Exposure to heavy metals, particularly cadmium (Cd), poses significant health risks because of their toxic effects and potential for bioaccumulation in living organisms. This study examined the biochemical and metabolomic changes induced by Cd exposure in an animal model via advanced liquid chromatography with tandem mass spectrometry (LC-MS/MS) and biochemical assays to reveal significant disruptions in lipid and amino acid metabolism as well as alterations in key metabolic pathways. Cd exposure led to significant weight loss, hyperglycemia, and insulin resistance, indicating its role in metabolic disorders such as diabetes. The accumulation of Cd in the liver and kidneys, identified via ICP-OES, corresponded with elevated levels of liver (ALT, AST) and kidney (BUN, creatinine) biomarkers, suggesting organ-specific toxicity. At the metabolic level, Cd exposure caused the accumulation of lipid metabolites such as ceramides and sphingolipids, which are associated with insulin resistance and broader metabolic impairments. Amino acid metabolism was also significantly disrupted, with increased concentrations of key amino acids such as phenylalanine, tryptophan, and arginine affecting pathways such as the urea cycle and Krebs cycle. These metabolic disturbances are linked to oxidative stress, systemic inflammation, and impaired glucose regulation, as evidenced by elevated CRP and IL-6 levels. The protective effects of resveratrol (RSV) were clearly demonstrated in this study. RSV treatment ameliorated Cd-induced biochemical and metabolic alterations, as shown by improved glycemic control, restored lipid profiles, and normalized amino acid concentrations. Additionally, RSV significantly reduced inflammatory markers and improved liver and kidney function, highlighting its antioxidant properties and potential as a therapeutic agent against Cd toxicity. However, RSV did not significantly reduce Cd accumulation in organs, indicating that its protective effects are related to mitigating oxidative damage and metabolic disruption rather than promoting Cd excretion. This study enhances our understanding of the molecular mechanisms underlying Cd-induced metabolic impairments and highlights the therapeutic potential of RSV in combating Cd toxicity. These findings underscore the need for further research into heavy metal exposure and its mitigation to protect human health, particularly in areas of environmental contamination.
接触重金属,尤其是镉(Cd),因其毒性作用以及在生物体内生物累积的可能性,会带来重大健康风险。本研究通过先进的液相色谱串联质谱法(LC-MS/MS)和生化分析,检测了动物模型中镉暴露诱导的生化和代谢组学变化,以揭示脂质和氨基酸代谢的显著紊乱以及关键代谢途径的改变。镉暴露导致显著体重减轻、高血糖和胰岛素抵抗,表明其在糖尿病等代谢紊乱中起作用。通过电感耦合等离子体发射光谱法(ICP-OES)确定,镉在肝脏和肾脏中的蓄积与肝脏(谷丙转氨酶、谷草转氨酶)和肾脏(血尿素氮、肌酐)生物标志物水平升高相对应,表明存在器官特异性毒性。在代谢水平上,镉暴露导致脂质代谢物如神经酰胺和鞘脂的蓄积,这些与胰岛素抵抗和更广泛的代谢损伤有关。氨基酸代谢也受到显著干扰,苯丙氨酸、色氨酸和精氨酸等关键氨基酸浓度增加,影响了尿素循环和三羧酸循环等途径。这些代谢紊乱与氧化应激、全身炎症和葡萄糖调节受损有关,血清C反应蛋白(CRP)和白细胞介素-6(IL-6)水平升高证明了这一点。本研究清楚地证明了白藜芦醇(RSV)的保护作用。RSV治疗改善了镉诱导的生化和代谢改变,表现为血糖控制改善、脂质谱恢复正常和氨基酸浓度正常化。此外,RSV显著降低了炎症标志物水平,改善了肝脏和肾脏功能,突出了其抗氧化特性以及作为抗镉毒性治疗剂的潜力。然而,RSV并未显著降低器官中镉的蓄积,表明其保护作用与减轻氧化损伤和代谢紊乱有关,而非促进镉的排泄。本研究增进了我们对镉诱导的代谢损伤潜在分子机制的理解,并突出了RSV在对抗镉毒性方面的治疗潜力。这些发现强调了进一步研究重金属暴露及其缓解措施以保护人类健康的必要性,特别是在环境污染地区。