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Background <p>Doxorubicin is a widely used anthracycline chemotherapeutic agent. Despite its high therapeutic value, its clinical role is limited by dose-dependent myocardial injury. Chronic inflammation and oxidative stress are key mechanisms of its cardiotoxic effects. The current study evaluates the cardioprotective effects of Taxifolin and Saroglitazar, individually and in combination, in a rat Model of doxorubicin-induced cardiotoxicity.</p> Methods <p>Wistar rats received doxorubicin (1.66&#xa0;mg/kg, i.p., every 48&#xa0;h) for 12 days to induce cardiotoxicity. Rats were treated orally with Taxifolin (50&#xa0;mg/kg), Saroglitazar (10&#xa0;mg/kg), their combination, and Carvedilol (30&#xa0;mg/kg). Cardiac function was assessed through electrocardiography and hemodynamic parameters (SAP, DAP, MAP). Antioxidant status (SOD, CAT, GSH, TBARS) and inflammatory markers (TNF-α, NLRP3) and PPAR-α were evaluated using biochemical, ELISA, and immunohistochemical methods. Morphometric ratios were calculated to assess cardiac hypertrophy. Molecular docking was conducted to determine ligand interaction with NF-κB, NLRP3, and PPAR-α.</p> Results <p>Doxorubicin administration led to significant ECG alterations, elevated TBARS levels, and suppressed antioxidant enzyme activity. Levels of TNF-α and NLRP3 rose markedly; on the contrary, PPAR-α expression declined. The combination of Taxifolin and Saroglitazar significantly restored oxidative balance, attenuated inflammatory markers, and improved histological and functional parameters. In silico docking confirmed favorable interactions of both agents with inflammatory and metabolic regulators.</p> Conclusion <p>Taxifolin and Saroglitazar exhibited complementary antioxidant and anti-inflammatory actions against doxorubicin-induced cardiac damage. Their combination conferred superior cardio-protection, potentially via modulation of NF-κB, NLRP3, and PPAR-α signaling. These findings warrant further exploration of their therapeutic synergy in the context of clinical cardiotoxicity.</p> Graphical Abstract <p></p>

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Cardioprotective Role of Taxifolin and Saroglitazar Against Doxorubicin Induced Cardiotoxicity in Wistar Rats: Evidence from In-silico, Hemodynamic, Biochemical and Histopathological Studies

  • 期刊论文

  • 发表日期：

    2026年4月18日

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  • Akshoo Rathi,
  • Lalit Parihar,
  • Mohit Nagar,
  • Sanjar Alam,
  • Ajay Pal Singh

摘要

Background

Doxorubicin is a widely used anthracycline chemotherapeutic agent. Despite its high therapeutic value, its clinical role is limited by dose-dependent myocardial injury. Chronic inflammation and oxidative stress are key mechanisms of its cardiotoxic effects. The current study evaluates the cardioprotective effects of Taxifolin and Saroglitazar, individually and in combination, in a rat Model of doxorubicin-induced cardiotoxicity.

Methods

Wistar rats received doxorubicin (1.66 mg/kg, i.p., every 48 h) for 12 days to induce cardiotoxicity. Rats were treated orally with Taxifolin (50 mg/kg), Saroglitazar (10 mg/kg), their combination, and Carvedilol (30 mg/kg). Cardiac function was assessed through electrocardiography and hemodynamic parameters (SAP, DAP, MAP). Antioxidant status (SOD, CAT, GSH, TBARS) and inflammatory markers (TNF-α, NLRP3) and PPAR-α were evaluated using biochemical, ELISA, and immunohistochemical methods. Morphometric ratios were calculated to assess cardiac hypertrophy. Molecular docking was conducted to determine ligand interaction with NF-κB, NLRP3, and PPAR-α.

Results

Doxorubicin administration led to significant ECG alterations, elevated TBARS levels, and suppressed antioxidant enzyme activity. Levels of TNF-α and NLRP3 rose markedly; on the contrary, PPAR-α expression declined. The combination of Taxifolin and Saroglitazar significantly restored oxidative balance, attenuated inflammatory markers, and improved histological and functional parameters. In silico docking confirmed favorable interactions of both agents with inflammatory and metabolic regulators.

Conclusion

Taxifolin and Saroglitazar exhibited complementary antioxidant and anti-inflammatory actions against doxorubicin-induced cardiac damage. Their combination conferred superior cardio-protection, potentially via modulation of NF-κB, NLRP3, and PPAR-α signaling. These findings warrant further exploration of their therapeutic synergy in the context of clinical cardiotoxicity.

Graphical Abstract