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April 7, 2023BiomedicinesOpen Access

Urolithin A’s Antioxidative, Anti-Inflammatory, and Antiapoptotic Activities Mitigate Doxorubicin-Induced Liver Injury in Wistar Rats

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Why the study?

The study investigated the mechanisms through which the gut microbiota metabolite urolithin A protects against doxorubicin-induced liver injury.

Does urolithin A mitigate doxorubicin-induced liver injury in Wistar rats?

Population

Wistar rats

Comparison

Urolithin A (2.5 or 5 mg kg-1 d-1) with doxorubicin vs doxorubicin alone

Design

Animal experiment

Follow-up

14 days

Authors

SKShahid KarimBMBatoul MadaniABAbdulhadi S. Burzangi

Discussion

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Overview

Hypothesis-generating for urolithin A in doxorubicin hepatotoxicity; human trials required before any clinical consideration.

Key Points

  • To investigate the protective mechanisms and therapeutic efficacy of urolithin A against doxorubicin-induced liver injury in Wistar rats.
  • Treated Wistar rats with doxorubicin (20 mg/kg IP on day 7) and daily urolithin A (2.5 or 5 mg/kg/day IP for 14 days).
  • Evaluated serum liver enzymes (AST, ALT, GGT), liver histopathology using H&E staining, tissue antioxidant enzymes (SOD, CAT), inflammatory markers (TNF-α, NF-kB, IL-6), and apoptotic markers (active caspase 3, cytochrome c oxidase).
  • Urolithin A supplementation significantly attenuated doxorubicin-induced hepatic histological damage and normalized elevated serum liver enzymes.
  • Hepatic antioxidant enzymes (SOD and CAT) were increased, whereas tissue levels of proinflammatory mediators (TNF-α, NF-kB, and IL-6) were significantly suppressed.
  • Treatment modulated hepatic levels of active caspase 3 and cytochrome c oxidase, indicating suppression of apoptotic cell death pathways.

Structured PICO

Does urolithin A mitigate doxorubicin-induced liver injury in Wistar rats?

P
Population
Wistar rats subjected to doxorubicin (DOX)-induced liver injury
I
Intervention
Urolithin A (URO A) administered intraperitoneally (2.5 or 5 mg/kg/day) for 14 days, with DOX (20 mg/kg) administered intraperitoneally on day 7
C
Comparator
Doxorubicin alone (implied control group)
O
Outcome
Liver injury assessed by serum levels of AST, ALT, and GGT, and histopathological characteristicssurrogate

Urolithin A demonstrates protective effects against doxorubicin-induced hepatotoxicity in a rat model through antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

Cite This Study

Karim et al. (2023) studied this question.

synapsesocial.com/papers/69dbdbcb5b363cdf1c8360dbhttps://doi.org/10.3390/biomedicines11041125
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Mokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis2021 · 23 citations
  2. 2Protective Effects of Dioscin Against Doxorubicin-Induced Hepatotoxicity Via Regulation of Sirt1/FOXO1/NF-κb Signal2019 · 135 citations
  3. 3Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro2009 · 382 citations
  4. 4The role of iron in doxorubicin-induced cardiotoxicity: recent advances and implication for drug delivery2021 · 52 citations
  5. 5Liver Injury Induced by Anticancer Chemotherapy and Radiation Therapy2013 · 132 citations