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Protective effect of baicalein alone and losartan–baicalein combination therapy on doxorubicin-induced hepatotoxicity in rats

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Abstract

Objective

Doxorubicin (DOX) is a widely used antineoplastic drug with several toxic effects. We investigated the protective effect of co-administration of baicalein (BL; a flavonoid) and losartan (LT; angiotensin receptor blocker) on DOX-induced hepatotoxicity.

Methods

Male Wistar albino rats were divided into these seven groups (n = 6): (1) Control group; (2) DOX group; (3) DOX + LT group (LT, 7 mg/kg/day orally); (4) DOX + BL low-dose group (BL, 5 mg/kg/day orally); (5) DOX + BL high-dose group (BL, 10 mg/kg/day orally); (6) DOX + LT + BL(5) low-dose group; and (7) DOX + LT + BL(10) high-dose group. After 2 weeks of LT and BL treatment, a dose of DOX (15 mg/kg, intraperitoneal) was administered to the rats in groups 2 to 6 and continued for seven more days.

Results

The use of serum levels of liver enzymes, tumor necrosis factor-α, interleukin (IL)-6, and IL1β and estimated the activity of thiobarbituric acid-reactive substances, glutathione, superoxide dismutase, catalase, and glutathione peroxidase in liver homogenates. In addition, we measured the activity of caspase-3, nitric oxide, inducible nitric oxide synthase, endothelial nitric oxide synthase, and nuclear factor kappa-B (NF-κB) p65 in hepatic cells and subjected the liver sections to histological examination. While the DOX-induced increase in serum liver enzymes, pro-inflammatory cytokines, and biomarkers was alleviated by BL and/or LT treatment, the BL + LT groups showed the most potent protective effects.

Conclusions

Our study demonstrates remarkable anti-oxidative and anti-inflammatory effects of BL and LT in rodents challenged with DOX. Concurrent administration of BL and LT showed a marked synergistic effect in restoration of histological features and alleviation of hepatic oxidative injury via inhibition of reactive oxygen species and anti-inflammatory mechanisms.

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Acknowledgements

This study has been supported by Jouf University under the following Grant: Project No. 39/647.

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Authors and Affiliations

  1. Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Jouf University, P.O. Box 2014, Sakaka, Al-Jouf, Saudi Arabia

    Ziad H. Al-Oanzi

  2. Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Jouf University, Qurayyat, Al-Jouf, Saudi Arabia

    Abdelbaset M. Elasbali

  3. Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi Arabia

    Nabil K. Alruwaili

  4. Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi Arabia

    Nasser Hadal Alotaibi & Abdulaziz I. Alzarea

  5. Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi Arabia

    Khalid S. Alharbi

  6. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Northern Border University, Rafha, Saudi Arabia

    Bader H. Alsuwayt

  7. Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam Bin Abdelaziz University, Al-Kharj, Saudi Arabia

    Maher M. Al-Enazi

Authors
  1. Ziad H. Al-Oanzi
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  2. Abdelbaset M. Elasbali
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  3. Nabil K. Alruwaili
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  4. Nasser Hadal Alotaibi
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  5. Khalid S. Alharbi
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  6. Abdulaziz I. Alzarea
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  7. Bader H. Alsuwayt
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  8. Maher M. Al-Enazi
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Corresponding author

Correspondence to Ziad H. Al-Oanzi.

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Conflict of interest

Ziad H. Al-Oanzi, Abdelbaset M. Elasbali, Nabil K. Alruwaili, Nasser Hadal Alotaibi, Khalid S. Alharbi, Abdulaziz I. Alzarea, Bader H. Alsuwayt, and Maher M. Al-Enazi declare that we have no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee at the Experimental Animal Center and House, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia (621-EACC-2016 dated 02-03-2016).

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Al-Oanzi, Z.H., Elasbali, A.M., Alruwaili, N.K. et al. Protective effect of baicalein alone and losartan–baicalein combination therapy on doxorubicin-induced hepatotoxicity in rats. Toxicol. Environ. Health Sci. 12, 45–54 (2020). https://doi.org/10.1007/s13530-020-00037-7

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  • DOI: https://doi.org/10.1007/s13530-020-00037-7

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