What question did this study set out to answer?

This research aims to determine if DDR can protect against doxorubicin-induced renal damage by targeting oxidative stress and apoptotic pathways.

February 28, 2026

Amelioration of doxorubicin-mediated nephrotoxicity through antioxidant and anti-apoptotic mechanisms of 5,4′-dihydroxy-6,8-dimethoxy-7-O-rhamnosylflavone

Q: What is the clinical evidence from this study?

Study design: Other. Population: Doxorubicin-induced nephrotoxicity (n=30). Intervention: 5,4′-dihydroxy-6,8-dimethoxy-7-O-rhamnosylflavone (DDR) vs. Control vehicle and DOX alone. Primary outcome: Tubular injury score (p=<0.001).

Key Result

High-dose DDR protected against doxorubicin-induced nephrotoxicity, reducing serum creatinine by 78% and normalizing tubular injury score (2.8 vs 14.8, p<0.001).

Key Points

This research aims to determine if DDR can protect against doxorubicin-induced renal damage by targeting oxidative stress and apoptotic pathways.
Male Swiss albino mice (n = 6/group) received control, DOX, DOX+DDR (25 or 50 mg/kg), or DDR alone for 6 weeks.
Measurement of renal function and oxidative stress markers, along with protein expression for key pathways, was conducted.
Histopathology analysis was performed using H&E and Masson's trichrome staining with injury scoring.
DOX caused severe nephrotoxicity, increasing serum creatinine by 347% and tubular injury score to 14.8 ± 1.4 (p < 0.001).
High-dose DDR improved renal function, decreasing creatinine by 78% and lowering injury score to 2.8 ± 0.9 (p < 0.001).
DDR also suppressed NOX-4 and reactivated NRF2, significantly reducing apoptosis markers.

Structured PICO

Does 5,4'-dihydroxy-6,8-dimethoxy-7-O-rhamnosylflavone (DDR) prevent doxorubicin-induced nephrotoxicity in mice?

Population

Male Swiss albino mice (n=6/group)

Intervention

5,4'-dihydroxy-6,8-dimethoxy-7-O-rhamnosylflavone (DDR) 25 or 50 mg/kg i.p. twice weekly, added to doxorubicin (2.5 mg/kg i.p. weekly for 6 weeks)

Comparator

Control vehicle; doxorubicin alone (2.5 mg/kg i.p. weekly for 6 weeks)

Outcome

Renal function (creatinine, urea, NGAL, KIM-1), oxidative stress markers, cytokines, protein expression, and histopathologysurrogate

DDR provides potent renoprotection against doxorubicin-induced nephrotoxicity in a preclinical mouse model.

Main Result

Absolute Event Rate: 2.8% vs 14.8%

p-value: p=<0.001

Abstract

Doxorubicin (DOX), a cornerstone chemotherapeutic, induces dose-limiting nephrotoxicity through NOX-4-mediated oxidative stress, inflammatory signalling, and apoptosis, thereby compromising its long-term clinical utility. This study investigated whether 5,4'-dihydroxy-6,8-dimethoxy-7-O-rhamnosylflavone (DDR), a bioactive flavonoid, protects against chronic DOX-induced renal injury. To evaluate DDR's renoprotective efficacy and elucidate its mechanistic involvement of NOX-4, NRF2, and apoptotic pathways. Male Swiss albino mice (n = 6/group) received: control vehicle, DOX (2.5 mg/kg i.p., weekly × 6 weeks), DOX + DDR (25 or 50 mg/kg i.p., twice weekly), or DDR alone. Renal function (creatinine, urea, NGAL, KIM-1), oxidative stress markers (MDA, SOD, CAT, GSH), cytokines (pNFκB, TNF-α, IL-6, IL-1β), and protein expression (NOX-4, NRF2, BCL2, BCL-XL, Caspase-3) were quantified. Histopathology employed H high-dose DDR restored renal function (creatinine ↓78%), normalized histopathology (score 2.8 ± 0.9, p < 0.001), suppressed NOX and reactivated NRF2, and prevented apoptosis. DDR provides potent, mechanistically defined renoprotection against DOX nephrotoxicity through multi-target modulation of oxidative, inflammatory, and apoptotic pathways. These preclinical findings support DDR's development as a clinically translatable chemotherapeutic adjuvant (Human equivalent dose: 2-4 mg/kg).

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