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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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