What is the clinical evidence from this study?

Study design: RCT. Population: Doxorubicin-induced cognitive impairment (n=40). Intervention: Sacubitril/valsartan vs. Doxorubicin (2.5 mg/kg). Primary outcome: Cognitive performance measured by behavioral tests (Y-maze and Novel Object Recognition tests) (null, 95% CI null, p=<0.05).

What does this research mean for the field?

Sacubitril/valsartan did not prevent doxorubicin-induced cognitive impairment and hippocampal damage in rats. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

What question did this study set out to answer?

The research aims to evaluate whether sacubitril/valsartan can reduce cognitive impairment caused by doxorubicin in an animal model.

January 9, 2026Frontiers in PharmacologyOpen Access

Sacubitril/valsartan fails to prevent doxorubicin-induced cognitive impairment and hippocampal oxidative, inflammatory, and apoptotic alterations in rats

Q: What are the key findings of this study?

Sacubitril/valsartan did not prevent doxorubicin-induced cognitive impairment and hippocampal damage in rats.

Q: What does this research mean for the field?

Sacubitril/valsartan did not prevent doxorubicin-induced cognitive impairment and hippocampal damage in rats. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

Q: What question did this study set out to answer?

The research aims to evaluate whether sacubitril/valsartan can reduce cognitive impairment caused by doxorubicin in an animal model.

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Key result

Sacubitril/valsartan did not prevent doxorubicin-induced cognitive impairment and hippocampal damage in rats.

Authors

MAMohrah Muteb AlresheediQassim University MAMaha Abdulrahman AldubayanQassim University

Discussion

Member takes

Implication

Demonstrates that sacubitril/valsartan fails to mitigate cognitive impairment in rats with doxorubicin-induced toxicity, suggesting limited neuroprotective effects.

Key Points

The research aims to evaluate whether sacubitril/valsartan can reduce cognitive impairment caused by doxorubicin in an animal model.
Forty male Wistar rats were divided into four groups: Control, DOX, VS, and DOX + VS.
Sacubitril/valsartan was administered orally, while doxorubicin was given intraperitoneally weekly for 4 weeks.
Cognitive performance was assessed, followed by biochemical and histological analyses of hippocampal tissues.
DOX + VS treatment led to significant weight loss and reduced survival compared to controls and VS alone.
Hippocampal oxidative, inflammatory, and apoptotic markers were significantly elevated in DOX and DOX + VS groups.
Histopathological analysis showed severe hippocampal damage in DOX + VS group similar to DOX alone, while VS alone and controls displayed less damage.

Study Design

Type

RCT (n=40)

Blinding

null

Randomization

Randomized

Multicenter

PICO

Population

Doxorubicin-induced cognitive impairment (n=40)

Intervention / Comparator

Sacubitril/valsartan vs Doxorubicin (2.5 mg/kg) (60 mg/kg)

Primary Outcome

Cognitive performance measured by behavioral tests (Y-maze and Novel Object Recognition tests) — null (null), p=<0.05

Main Result

Effect estimate: null (95% CI null)

p-value: p=<0.05

Limitations

No valsartan-only treatment group to assess individual effects
Study limited to male rats which may restrict generalizability

Cite This Study

Alresheedi et al. (2026) conducted an RCT in Doxorubicin-induced cognitive impairment (n=40). Sacubitril/valsartan vs. Doxorubicin (2.5 mg/kg) was evaluated on Cognitive performance measured by behavioral tests (Y-maze and Novel Object Recognition tests) (null, 95% CI null, p=<0.05). Sacubitril/valsartan did not prevent doxorubicin-induced cognitive impairment and hippocampal damage in rats.

synapsesocial.com/papers/69612fd330ef6c21f6853cd6 https://doi.org/10.3389/fphar.2025.1732842

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Implication

Demonstrates that sacubitril/valsartan fails to mitigate cognitive impairment in rats with doxorubicin-induced toxicity, suggesting limited neuroprotective effects.

Sacubitril/valsartan fails to prevent doxorubicin-induced cognitive impairment and hippocampal oxidative, inflammatory, and apoptotic alterations in rats

Discussion

Member takes

Implication

Key Points

Study Design

PICO

Main Result

Limitations

Cite This Study

Sacubitril/valsartan fails to prevent doxorubicin-induced cognitive impairment and hippocampal oxidative, inflammatory, and apoptotic alterations in rats

Discussion

Member takes

Implication

Key Points

Study Design

PICO

Main Result

Limitations

Cite This Study

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