Effects of Hydroxytyrosol Against Doxorubicin-Induced Hepatotoxicity Through Alterations in Dardarin and Podocalyxin Expression in Rats

Q: What are the key findings of this study?

Hydroxytyrosol significantly attenuated doxorubicin-induced hepatic fibrosis and reduced LRRK2 expression (0.09 vs 0.29, p<0.001) compared to doxorubicin alone in rats.

Q: What is the clinical evidence from this study?

Population: Doxorubicin-induced hepatotoxicity (n=28). Intervention: Hydroxytyrosol vs. Doxorubicin alone. Primary outcome: LRRK2 expression (histoscore) (p=<0.001).

Q: What does this research mean for the field?

Hydroxytyrosol mitigates doxorubicin-induced hepatotoxicity in rats, potentially by reducing the expression of dardarin (LRRK2) and podocalyxin (PODX). Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

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

To investigate whether hydroxytyrosol protects against doxorubicin-induced liver injury in rats through alterations in dardarin (LRRK2) and podocalyxin (PODX) expression.

Elif Onat; Nevin Kocaman; Erkan Yilmaz; Serhat Hançer

doi:10.7759/cureus.109870

May 29, 2026CureusOpen Access

Effects of Hydroxytyrosol Against Doxorubicin-Induced Hepatotoxicity Through Alterations in Dardarin and Podocalyxin Expression in Rats

View Full Paper

Ask AI

Bookmark

Share

Key result

Hydroxytyrosol attenuates doxorubicin-induced hepatic fibrosis and cuts LRRK2 expression ~69% in rats.

P<0.001
n=28

Figures

Why the study?

The study investigated whether dardarin (LRRK2) and podocalyxin (PODX) contribute to the hepatoprotective effects of hydroxytyrosol against doxorubicin-induced liver injury.

Does hydroxytyrosol prevent doxorubicin-induced hepatotoxicity in female Sprague Dawley rats?

Key Points

To investigate whether hydroxytyrosol protects against doxorubicin-induced liver injury in rats through alterations in dardarin (LRRK2) and podocalyxin (PODX) expression.
Twenty-eight female Sprague Dawley rats were randomly assigned to four groups: Control, HT, DOX, and DOX+HT.
DOX (10 mg/kg) was given as a single intraperitoneal dose on day 1, while HT (100 mg/kg/day) was administered orally for 28 days.
Liver tissues were collected at day 28 for histopathological scoring using hematoxylin-eosin and Masson's trichrome staining, alongside immunohistochemical quantification of LRRK2 and PODX.
DOX administration significantly increased hepatic fibrosis scores to 6.57±0.53 (vs 1.71±0.49 in controls), leukocyte infiltration to 6.86±0.38 (vs 1.29±0.49), congestion to 6.71±0.49 (vs 2±0.58), and sinusoidal dilatation to 6.86±0.38 (vs 2±0.58; p<0.001 for all).
Co-treatment in the DOX+HT group significantly attenuated structural liver injury compared to DOX alone, lowering fibrosis to 2.86±0.69, leukocyte infiltration to 1.71±0.49, congestion to 3.71±0.49, and sinusoidal dilatation to 3.57±0.53 (p<0.001).
DOX upregulated immunohistochemical expression of LRRK2 (0.29±0.08 vs 0.07±0.03 in controls) and PODX (1.54±0.32 vs 0.19±0.09; p<0.001), whereas HT co-administration significantly reduced both markers to 0.09±0.02 and 0.66±0.17, respectively (p<0.001 vs DOX).

Structured PICO

Does hydroxytyrosol prevent doxorubicin-induced hepatotoxicity in female Sprague Dawley rats?

P

Population

28 female Sprague Dawley rats

I

Intervention

Hydroxytyrosol (HT) 100 mg/kg/day orally for 28 days following doxorubicin (DOX) 10 mg/kg intraperitoneally on day 1

C

Comparator

Doxorubicin (DOX) 10 mg/kg intraperitoneally on day 1 alone, HT alone, and Control

O

Outcome

Histopathological evaluation of liver tissues, including LRRK2 and PODX expression levels, hepatic fibrosis, leukocyte infiltration, congestion, and sinusoidal dilatationsurrogate

Main Result

Absolute Event Rate: 0.09% vs 0.29%

p-value: p=<0.001

Limitations

Relatively small sample size
Use of only female rats
Molecular techniques such as Western blotting or RT-qPCR were not employed to quantitatively confirm expression changes
Study focused on short-term effects

Implication

Hydroxytyrosol demonstrates hepatoprotective effects against doxorubicin-induced liver injury in rats, associated with reduced LRRK2 and PODX expression.

Abstract

Introduction: This study investigated whether dardarin (LRRK2) and podocalyxin (PODX) contribute to the hepatoprotective effects of hydroxytyrosol (HT) against doxorubicin (DOX)-induced liver injury in rats. Methods: Twenty-eight female Sprague Dawley rats were randomly assigned to four groups: Control, HT, DOX, and DOX+HT. DOX (10 mg/kg) was administered intraperitoneally as a single dose on day 1. HT was given orally at 100 mg/kg/day for 28 days. In the DOX+HT group, animals received DOX on day 1 followed by daily oral HT for 28 days. At the end of the experiment, liver tissues were collected for histopathological evaluation, and all findings were statistically analyzed. Results: Histopathological assessments showed significantly elevated LRRK2 and PODX expression levels in the DOX group, while co-treatment with HT markedly reduced these increases (p<0.001). Additionally, DOX-induced hepatic fibrosis, leukocyte infiltration, congestion, and sinusoidal dilatation were substantially alleviated in the DOX+HT group (p<0.001). Conclusion: HT demonstrated beneficial effects on histopathological and immunohistochemical changes in DOX-induced liver injury. The reduction in LRRK2 and PODX expression implies that these molecules may be involved in the mechanisms underlying HT-mediated hepatoprotection. These findings highlight the potential therapeutic value of HT in mitigating DOX-associated hepatotoxicity.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Onat et al. (2026) studied Doxorubicin-induced hepatotoxicity (n=28). Hydroxytyrosol vs. Doxorubicin alone was evaluated on LRRK2 expression (histoscore) (p=<0.001). Hydroxytyrosol significantly attenuated doxorubicin-induced hepatic fibrosis and reduced LRRK2 expression (0.09 vs 0.29, p<0.001) compared to doxorubicin alone in rats.

synapsesocial.com/papers/6a1bd5425783ba022b6fe398 https://doi.org/10.7759/cureus.109870

View Full Paper

Ask AI

Bookmark

Share

Effects of Hydroxytyrosol Against Doxorubicin-Induced Hepatotoxicity Through Alterations in Dardarin and Podocalyxin Expression in Rats

Figures

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Effects of Hydroxytyrosol Against Doxorubicin-Induced Hepatotoxicity Through Alterations in Dardarin and Podocalyxin Expression in Rats

Figures

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading