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Bioprospecting hydroxylated chalcones in in vitro model of ischemia-reoxygenation and probing NOX4 interactions via molecular docking

  • Arif Ali ORCID logo , Igor Moreira de Almeida , Emanuel Paula Magalhães , Jesyka Macedo Guedes , Francisco Ferdinando Mesquita Cajazeiras , Marcia Machado Marinho , Emmanuel Silva Marinho , Ramon Róseo Paula Pessoa Bezerra de Menezes , Tiago Lima Sampaio , Hélcio Silva dos Santos , Geraldo Bezerra da Silva Júnior and Alice Maria Costa Martins ORCID logo EMAIL logo
Published/Copyright: December 23, 2024

Abstract

Ischemia/reperfusion injury (I/R) is a leading cause of acute kidney injury (AKI) in conditions like kidney transplants, cardiac surgeries, and nephrectomy, contributing to high global mortality and morbidity. This study aimed to analyze the protective effects of 2′-hydroxychalcones in treating I/R-induced AKI by targeting key pathological pathways. Considering strong antioxidant action along with other pharmacological roles of chalcone derivatives, six 2′-hydroxychalcones were synthesized via Claisen-Schmidt condensation and analyzed for their protective effects in an I/R induced AKI model using HK-2 cells. Among six 2′-hydroxychalcones, chalcone A4 significantly increased the HK-2 cells viability compared to I/R group. Chalcone A4 reduced the cell death events by reducing generation of cytoplasmic ROS and mitochondrial transmembrane potential. It also increased GSH and SOD activity while reducing TBARS levels, indicating strong antioxidant action. Scanning electron microscope images showed that chalcone A4 reversed I/R-induced morphological changes in HK-2 cells, including apoptotic blebbing and cytoplasmic fragmentation. Furthermore, in silico studies revealed interactions with NADPH oxidase 4, further supporting its protective role in I/R-induced AKI. These results showed that chalcone A4 possess potential protective action against I/R induced cellular damage possibly due to its strong antioxidant action and potential interaction with NOX4 subunit of NADPH oxidase.


Corresponding author: Alice Maria Costa Martins, Postgraduate Program in Pharmacology, Federal University of Ceara, Fortaleza, CE, Brazil; and Department of Clinical and Toxicological Analysis, Federal University of Ceara, Rua Capitão Francisco Pedro 1210 Rodolfo Teófilo, 60430-170, Fortaleza, CE, Brazil, E-mail: .

Award Identifier / Grant number: ITR-0214-00060.01.00/23, UNI-0210-00337.01.00/23,

Award Identifier / Grant number: 306008/2022-0

Acknowledgments

The author acknowledges Dr. Hélcio Silva dos Santos and financial support from the PQ/CNPq and FUNCAP.

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. Arif Ali: Wrote original draft, Investigation Igor Moreira de Almeida, Emanuel Paula Magalhães, Jesyka Macedo Guedes and Francisco Ferdinando Mesquita Cajazeira: Investigation Marcia Machado Marinho, Emmanuel Silva Marinho, Ramon Róseo Paula Pessoa Bezerra de Menezes, Tiago Lima Sampaio, Hélcio Silva dos Santos: Methodology, interpretation and data analysis Geraldo Bezerra da Silva Júnior: Supervision, review Alice Maria Costa Martins: Conception, Funding, Project management and supervision.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: PQ/CNPq (Grant#: 306008/2022-0) FUNCAP (Grants#: ITR-0214-00060.01.00/23, UNI-0210-00337.01.00/23, FPD-0213-00088.01.00/23).

  7. Data availability: All data generated or analyzed during this study are included in this published article [and its supplementary information files].

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Received: 2024-05-07
Accepted: 2024-11-18
Published Online: 2024-12-23
Published in Print: 2024-12-17

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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