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<p>Leflunomide (LF) is an immunomodulator classified as a disease-modifying anti-rheumatic agent. Its mechanisms of action include inhibition of dihydroorotate dehydrogenase in lymphocytes, resulting in immunosuppressive effects, and blocking tyrosine kinase activation, generating anti-inflammatory effects. This study aimed to study biochemical parameters 24&#xa0;h after leflunomide administration to <i>Nauphoeta cinerea</i> (Cockroach) model, focusing on toxicity assessment. Biochemical analyses were performed, and molecular docking studies were conducted with the proteins 6VCD, 2B3X, and 2B3Y. Leflunomide altered biochemical parameters by increasing markers such as PSH, NPSH, TBARS, and iron levels, suggesting that LF may induce oxidative stress. This was supported by a dose-dependent increase in PSH, indicating an adaptive defense response. Furthermore, a significant increase in NPSH was observed at 128&#xa0;µg/mL coupled with increased lipid peroxidation and elevated iron levels at 256&#xa0;µg/mL. Additionally, LF exhibited high molecular activity by interacting with the target proteins, presenting major alkyl-type bonds, in addition to the interaction of fluorine with 2 proteins (6VCD and 2B3Y). In conclusion, leflunomide appears to induce oxidative stress in a dose-dependent manner, triggering adaptive defense responses and altering key biochemical markers.</p>

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Integrative biochemical and computational analysis of leflunomide-induced redox alterations in Nauphoeta cinerea

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月18日

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  • Carlos Alonso Leite dos Santos,
  • Antonia Adeublena de Araújo Monteiro,
  • Bárbara Rayanne da Silva Teles,
  • Jean-Paul Kamdem,
  • Antonia Eliene Duarte,
  • Haifa A. Alqhtani,
  • Mostafa R. Abukhadra,
  • Ahmed A. Allam,
  • Mohammad Ibrahim

摘要

Leflunomide (LF) is an immunomodulator classified as a disease-modifying anti-rheumatic agent. Its mechanisms of action include inhibition of dihydroorotate dehydrogenase in lymphocytes, resulting in immunosuppressive effects, and blocking tyrosine kinase activation, generating anti-inflammatory effects. This study aimed to study biochemical parameters 24 h after leflunomide administration to Nauphoeta cinerea (Cockroach) model, focusing on toxicity assessment. Biochemical analyses were performed, and molecular docking studies were conducted with the proteins 6VCD, 2B3X, and 2B3Y. Leflunomide altered biochemical parameters by increasing markers such as PSH, NPSH, TBARS, and iron levels, suggesting that LF may induce oxidative stress. This was supported by a dose-dependent increase in PSH, indicating an adaptive defense response. Furthermore, a significant increase in NPSH was observed at 128 µg/mL coupled with increased lipid peroxidation and elevated iron levels at 256 µg/mL. Additionally, LF exhibited high molecular activity by interacting with the target proteins, presenting major alkyl-type bonds, in addition to the interaction of fluorine with 2 proteins (6VCD and 2B3Y). In conclusion, leflunomide appears to induce oxidative stress in a dose-dependent manner, triggering adaptive defense responses and altering key biochemical markers.