Bioprospecting hydroxylated chalcones in in vitro model of ischemia-reoxygenation and probing NOX4 interactions via molecular docking
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Arif Ali
, 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
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.
Award Identifier / Grant number: ITR-0214-00060.01.00/23, UNI-0210-00337.01.00/23,
Funding source: Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
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.
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Research ethics: Not applicable.
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Informed consent: Not applicable.
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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.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The authors state no conflict of interest.
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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).
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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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Articles in the same Issue
- Frontmatter
- Review
- Structure, function, and recombinant production of EGFL7
- Research Articles/Short Communications
- Protein Structure and Function
- Zinc and copper effect mechanical cell adhesion properties of the amyloid precursor protein
- The BCL11A transcription factor stimulates the enzymatic activities of the OGG1 DNA glycosylase
- Cell Biology and Signaling
- Bioprospecting hydroxylated chalcones in in vitro model of ischemia-reoxygenation and probing NOX4 interactions via molecular docking
- Carnosic acid prevents heat stress-induced oxidative damage by regulating heat-shock proteins and apoptotic proteins in mouse testis
- Novel Techniques
- Simultaneous spectral illumination of microplates for high-throughput optogenetics and photobiology
- A platform for the early selection of non-competitive antibody-fragments from yeast surface display libraries
Articles in the same Issue
- Frontmatter
- Review
- Structure, function, and recombinant production of EGFL7
- Research Articles/Short Communications
- Protein Structure and Function
- Zinc and copper effect mechanical cell adhesion properties of the amyloid precursor protein
- The BCL11A transcription factor stimulates the enzymatic activities of the OGG1 DNA glycosylase
- Cell Biology and Signaling
- Bioprospecting hydroxylated chalcones in in vitro model of ischemia-reoxygenation and probing NOX4 interactions via molecular docking
- Carnosic acid prevents heat stress-induced oxidative damage by regulating heat-shock proteins and apoptotic proteins in mouse testis
- Novel Techniques
- Simultaneous spectral illumination of microplates for high-throughput optogenetics and photobiology
- A platform for the early selection of non-competitive antibody-fragments from yeast surface display libraries