Startseite Influence of Clerodendrum volubile leaf extract on doxorubicin-induced toxicity and inhibition of carbonyl reductase mediated metabolism
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Influence of Clerodendrum volubile leaf extract on doxorubicin-induced toxicity and inhibition of carbonyl reductase mediated metabolism

  • Olorunfemi R. Molehin EMAIL logo , Kehinde A. Idowu , Ayonposi B. Olaoye , Aderonke E. Fakayode und Oluwatumininu O. Adesua
Veröffentlicht/Copyright: 10. Mai 2021

Abstract

Objectives

Doxorubicin (DOX) is a commonly used chemotherapeutic drug. However, its non-target organ toxicities pose a serious problem. This study is to assess the protective role of Clerodendrum volubile leaf extract (CVE) against DOX-induced toxicities in rats. In addition, the inhibitory activities of three phytochemical compounds (Rutin, Gallic acid and Rosmarinic acid) from CVE against Carbonyl reductase 1 (CBR1) were examined.

Methods

Rats were randomly divided into 5 groups: (a) Control group rats were given 0.9% NaCl as vehicle, (b) DOX group: A single dose of DOX (25 mg/kg; i.p.) was administered and rats were sacrificed 4 days after DOX injection, while groups (c–e) CVE-treated DOX rat groups were given 125, 250 and 500 mg/kg body weight of extracts orally for 12 consecutive days; 8 days before, and 4 days after the DOX administration. Computational techniques were used to determine the inhibitory activities of the compounds against CBR1.

Results

DOX intoxication caused a significant increase (p<0.05) in serum marker enzymes: ALT, AST, ALP, LDH, CK activities. The levels of liver and heart tissues antioxidant parameters: GPx, SOD, CAT, and GSH were significantly (p<0.05) decreased in DOX-intoxicated rats with concomitant elevation of malondialdehyde levels. Pretreatment with CVE reversed the above trends. From the structural analysis, Rutin and RSA exhibited the highest binding free energies against CBR1, and also exhibited structural stability when bound with CBR1.

Conclusions

Our study indicates the protective effect of CVE when used in combination with doxorubicin thus improving its chemotherapeutic application via inhibition of CBR-mediated metabolism.


Corresponding author: Olorunfemi R. Molehin, PhD, AMRSC, Department of Biochemistry, Faculty of Science, Ekiti State University, Ado-Ekiti, P.M.B. 5363, Ado-Ekiti, 360001, Nigeria, Phone: +234 803 462 1267, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All the authors read and approved this submitted manuscript. The authors have also accepted responsibility for the entire content of this manuscript.

  3. Competing interests: The funding organization (s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

  4. Informed consent: Not applicable.

  5. Ethical approval: These ethic regulations were diligently followed during the experiment. This study also conforms to our institutional protocols of The Research and Ethics Committee, of the Office of Research and Development, Ekiti State University, Ado-Ekiti, Nigeria (ORD/AD/EAC/19/0026).

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Received: 2020-07-27
Accepted: 2021-02-15
Published Online: 2021-05-10

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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