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Protective mechanisms of protocatechuic acid against doxorubicin-induced nephrotoxicity in rat model

  • Olorunfemi R. Molehin EMAIL logo , Anne A. Adeyanju , Stephen A. Adefegha , Ajibade O. Oyeyemi and Kehinde A. Idowu
Published/Copyright: July 8, 2019

Abstract

Background

Doxorubicin (DOX) induces toxicity in many tissues/organs, including the heart, kidney and so on. This study was designed to evaluate the modulatory effects of protocatechuic acid (PCA) against DOX-induced nephrotoxicity in rats. Animals were randomly grouped into five groups.

Methods

Group 1 served as the normal control (CTR). A single dose of DOX at 20 mg/kg was administered intraperitoneally (i.p.) to animals in Group 2. Groups 3 and 4 were pretreated with PCA for 5 days (doses of 10 and 20 mg/kg body weight, respectively) after which DOX was injected (PCA-10 + DOX and PCA-20 + DOX). Group 5 received PCA only at a dose of 20 mg/kg body weight (PCA-20).

Results

The results revealed significant elevations (p < 0.05) in malondialdehyde content, expressions of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX2) in the kidney. Likewise, increased serum levels of creatinine and urea of DOX group were observed. A significant decrease (p < 0.05) in glutathione (GSH) level and antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione s- transferase (GST) activities in the kidney were observed compared with the control. Pretreatment with PCA (10 and 20 mg/kg, p.o.) for 5 days prior to the i.p. injection of DOX reduced MDA levels, modulated iNOS and COX2 activities and improved kidney function markers as well as oxidative stress parameters. Findings from the histopathology studies confirms the protective effects of PCA on DOX-induced damage on the kidney cells.

Conclusions

This study has demonstrated the anti-inflammatory and antioxidative properties of PCA, which could be part of its possible protective mechanisms against nephrotoxicity induced by DOX.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved its submission. Every author listed in this manuscript participated from the execution of the experiment to the writing of this manuscript.

  2. Research funding: This study did not receive any form of financial funding from any individual or organization.

  3. Competing interests: There is no competing interest among the authors or anybody involved in this experimentation.

  4. Ethical approval: The research related to animals’ use has complied with all the relevant national regulations and institutional policies for the care and use of animals as stipulated by the published guidelines of European Union directive (EU Directive 2010/63/EU).

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Received: 2018-09-10
Accepted: 2019-06-14
Published Online: 2019-07-08

© 2019 Walter de Gruyter GmbH, Berlin/Boston

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