What question did this study set out to answer?

Investigate the protective effects of CUR-NP against nephrotoxicity caused by doxorubicin in male rats.

January 25, 2026Open Access

Aryl Hydrocarbon Receptor (AhR) and Vascular Endothelial Growth Factor (VEGF) Crosstalk in Doxorubicin Nephrotoxicity: Mechanisms and Therapeutic Perspectives

Key Result

CUR-NP treatment improved kidney function and normalized oxidative stress markers in DOX-induced renal injury in rats, countering VEGF/AhR pathway disruption.

Key Points

Investigate the protective effects of CUR-NP against nephrotoxicity caused by doxorubicin in male rats.
Four groups of Wistar albino rats were formed for the study.
CUR-NP was administered orally for two weeks at a dose of 80 mg/kg.
Doxorubicin was injected as a single dose of 15 mg/kg on day seven of the study.
Renal function and oxidative stress markers were assessed post-treatment.
DOX increased circulating creatinine and urea levels, indicating kidney dysfunction.
CUR-NP treatment significantly improved kidney function and normalized oxidative stress markers.
Histological analysis showed preservation of renal structure with CUR-NP, contrasting with damage from DOX.
VEGF and AhR expression was significantly reduced with CUR-NP treatment.

Structured PICO

Does Nanocurcumin prevent Doxorubicin-induced renal injury in male rats?

Population

32 male Wistar albino rats

Intervention

Nanocurcumin (CUR-NP) 80 mg/kg dissolved in 1% CMC administered by oral gavage for two weeks, with a single dose of Doxorubicin (DOX) 15 mg/kg i.p. injected on day seven

Comparator

Doxorubicin (DOX) alone

Outcome

Renal function markers (circulating creatinine, urea, and urea-nitrogen)surrogate

Nanocurcumin demonstrates a protective effect against doxorubicin-induced nephrotoxicity in rats by modulating the VEGF/AhR pathway, reducing oxidative stress, and decreasing inflammation.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Doxorubicin (DOX), a widely used chemotherapeutic, is constrained by its nephrotoxicity, characterized by endothelial injury, inflammation, and oxidative stress. Vascular endothelial growth factor (VEGF) signaling in the kidney serves a dual function. Under normal conditions, it supports the survival of glomerular endothelial cells and maintains vascular stability, but when excessively activated, it disrupts angiogenesis and contributes to kidney injury. In this context, we hypothesize that Nanocurcumin (CUR-NP), a nano-formulated curcumin derivative with enhanced bioavailability, can modulate the VEGF pathway and restore regular renal activity. Thus, this study aims to explore the potential protective effect of CUR-NP on DOX-induced renal injury in male rats. Thirty-two Wistar albino rats were used and distributed into four groups. CUR-NP (80 mg/kg dissolved in 1% CMC) was administered by oral gavage for two weeks. A single dose of DOX (15 mg/kg) (i.p.) was injected on day seven of the study. Results showed that DOX increased the circulating creatinine, urea, and urea-nitrogen levels, while pretreatment with CUR-NP markedly alleviated kidney function. In addition, CUR-NP treatment significantly normalized oxidative stress markers in renal tissues, such as NO, GSH, and SOD, and improved renal pro-inflammatory mediators, TNF-α, IL-6, and NF-κB-p65. DOX caused degeneration of glomeruli and tubules with degenerated epithelial lining and casts in their lumens. Conversely, CUR-NP maintained standard tubular and glomerular structure. Immunohistochemistry showed that DOX strongly upregulated VEGF and AhR, while CUR-NP markedly reduced their expression, countering VEGF/AhR pathway disruption and helping restore physiological signaling.

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