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Background <p>Doxorubicin (DOX) is a widely prescribed chemotherapeutic agent, but its therapeutic use is frequently restricted due to its harmful effects on the kidneys. This research evaluated the nephroprotective properties of alantolactone (ATL), a naturally sourced sesquiterpene lactone, in a rat model of DOX-induced kidney injury, along with computational analysis of its molecular binding interactions.</p> Methods and results <p>Male Wistar rats were randomly assigned to five groups: Control, ATL (10), DOX, ATL (5) + DOX, and ATL (10) + DOX. The Control and DOX groups received 0.5% sodium carboxymethyl cellulose orally for 18 days, whereas ATL was given orally at 10&#xa0;mg/kg in the ATL-alone group. ATL was also administered orally at 5 or 10&#xa0;mg/kg in the respective co-treatment groups. On day 17, DOX (20&#xa0;mg/kg, i.p.) was administered to the DOX and co-treated animals. Renal function was assessed through serum biomarkers; oxidative stress (MDA, SOD, CAT), inflammatory markers (IL-6, TNF-α, NF-κB p65), and apoptosis-related genes (Bax, Bcl-2) were evaluated using biochemical methods, immunohistochemistry and qRT-PCR. Expression of Nrf2 and HO-1 was analysed, and molecular docking assessed interactions of ATL and DOX with Keap1 and TNF-α. ATL co-administration significantly alleviated DOX-induced renal impairment by reducing oxidative stress, inflammation, and apoptotic responses, while enhancing Nrf2 and HO-1 expression. Docking studies demonstrated strong binding affinity of ATL to Keap1 and TNF-α.</p> Conclusion <p>ATL confers nephroprotection against DOX-induced toxicity, potentially through its antioxidant, anti-inflammatory, and anti-apoptotic effects linked to Nrf2 and HO-1 activation.</p> Graphical Abstract <p></p>

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Alantolactone protects against doxorubicin-induced nephrotoxicity by modulating Nrf2/HO-1, NF-κB, and Bax/Bcl-2 activity: molecular and in silico insights

  • 期刊论文

  • 发表日期：

    2025年6月4日

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  • Mohammed F. Abuzinadah,
  • Rasheed A. Shaik,
  • Aftab Ahmad,
  • Mohammed Nazrul Islam,
  • Basma G. Eid

摘要

Background

Doxorubicin (DOX) is a widely prescribed chemotherapeutic agent, but its therapeutic use is frequently restricted due to its harmful effects on the kidneys. This research evaluated the nephroprotective properties of alantolactone (ATL), a naturally sourced sesquiterpene lactone, in a rat model of DOX-induced kidney injury, along with computational analysis of its molecular binding interactions.

Methods and results

Male Wistar rats were randomly assigned to five groups: Control, ATL (10), DOX, ATL (5) + DOX, and ATL (10) + DOX. The Control and DOX groups received 0.5% sodium carboxymethyl cellulose orally for 18 days, whereas ATL was given orally at 10 mg/kg in the ATL-alone group. ATL was also administered orally at 5 or 10 mg/kg in the respective co-treatment groups. On day 17, DOX (20 mg/kg, i.p.) was administered to the DOX and co-treated animals. Renal function was assessed through serum biomarkers; oxidative stress (MDA, SOD, CAT), inflammatory markers (IL-6, TNF-α, NF-κB p65), and apoptosis-related genes (Bax, Bcl-2) were evaluated using biochemical methods, immunohistochemistry and qRT-PCR. Expression of Nrf2 and HO-1 was analysed, and molecular docking assessed interactions of ATL and DOX with Keap1 and TNF-α. ATL co-administration significantly alleviated DOX-induced renal impairment by reducing oxidative stress, inflammation, and apoptotic responses, while enhancing Nrf2 and HO-1 expression. Docking studies demonstrated strong binding affinity of ATL to Keap1 and TNF-α.

Conclusion

ATL confers nephroprotection against DOX-induced toxicity, potentially through its antioxidant, anti-inflammatory, and anti-apoptotic effects linked to Nrf2 and HO-1 activation.

Graphical Abstract