Combined effects of vitamin D3 and dioxopiperidinamide derivative on lipid homeostasis, inflammatory pathways, and redox imbalance in non‐alcoholic fatty liver disease in vivo zebrafish model.

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Title: Combined effects of vitamin D3 and dioxopiperidinamide derivative on lipid homeostasis, inflammatory pathways, and redox imbalance in non‐alcoholic fatty liver disease in vivo zebrafish model.
Authors: Dharshan, Santhanam Sanjai1 (AUTHOR), Ramamurthy, Karthikeyan1 (AUTHOR), Kaliraj, Salamuthu2 (AUTHOR), Manikandan, Krishnan3 (AUTHOR), Chitra, Vellapandian4 (AUTHOR), Rajagopal, Rajakrishnan5 (AUTHOR), Alfarhan, Ahmed5 (AUTHOR), Namasivayam, S.Karthick Raja6 (AUTHOR) biologiask@gmail.com, Kathiravan, Muthu Kumaradoss7 (AUTHOR) drmkkathir@gmail.com, Arockiaraj, Jesu1 (AUTHOR) jesuaraj@gmail.com
Source: Biotechnology & Applied Biochemistry. Apr2025, Vol. 72 Issue 2, p320-339. 20p.
Subjects: Fatty liver, Cholecalciferol, Reactive oxygen species, Therapeutics, Inflammatory mediators
Abstract: Liver damage and metabolic dysfunctions, the defining features of non‐alcoholic fatty liver disease (NAFLD), are marked by inflammation, oxidative stress, and excessive hepatic fat accumulation. The current therapeutic approaches for NAFLD are limited, necessitating exploring novel treatment strategies. Dioxopiperidinamide derivatives, particularly DOPA‐33, have shown effective anti‐inflammatory and antioxidant properties, potentially offering therapeutic benefits against NAFLD. This study investigated the combined potential of vitamin D3 (Vit D3) and DOPA‐33 in treating NAFLD. The network pharmacology analysis identified key NAFLD targets modulated by Vit D3 and DOPA‐33, emphasizing their potential mechanisms of action. In NAFLD‐induced zebrafish models, Vit D3 and DOPA‐33 significantly reduced hepatic lipid accumulation, oxidative stress, and apoptosis, demonstrating superior efficacy over individual treatments. The treatment also lowered reactive oxygen species (ROS) levels, decreased liver damage, and enhanced antioxidant defense mechanisms. Moreover, behavioral analyses showed improved locomotion and reduced weight gain in treated zebrafish. Biochemical analyses revealed lower triglycerides (TG) and glucose levels with improved oxidative markers. Furthermore, histological analyses indicated reduced hepatic steatosis and inflammation, with decreased expression of lipogenesis‐related genes and inflammatory mediators. Finally, high‐performance liquid chromatography (HPLC) confirmed a significant reduction in hepatic cholesterol levels, indicating the effectiveness of the combination therapy in addressing key NAFLD‐related dyslipidemias. These findings suggest that Vit D3 + DOPA‐33 targets pathways involved in lipid metabolism, inflammation, and oxidative stress by offering a promising therapeutic approach for NAFLD. [ABSTRACT FROM AUTHOR]
Copyright of Biotechnology & Applied Biochemistry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
  Group: Ti
  Data: Combined effects of vitamin D3 and dioxopiperidinamide derivative on lipid homeostasis, inflammatory pathways, and redox imbalance in non‐alcoholic fatty liver disease in vivo zebrafish model.
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  Data: <searchLink fieldCode="AR" term="%22Dharshan%2C+Santhanam+Sanjai%22">Dharshan, Santhanam Sanjai</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ramamurthy%2C+Karthikeyan%22">Ramamurthy, Karthikeyan</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kaliraj%2C+Salamuthu%22">Kaliraj, Salamuthu</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Manikandan%2C+Krishnan%22">Manikandan, Krishnan</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chitra%2C+Vellapandian%22">Chitra, Vellapandian</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rajagopal%2C+Rajakrishnan%22">Rajagopal, Rajakrishnan</searchLink><relatesTo>5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Alfarhan%2C+Ahmed%22">Alfarhan, Ahmed</searchLink><relatesTo>5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Namasivayam%2C+S%2EKarthick+Raja%22">Namasivayam, S.Karthick Raja</searchLink><relatesTo>6</relatesTo> (AUTHOR)<i> biologiask@gmail.com</i><br /><searchLink fieldCode="AR" term="%22Kathiravan%2C+Muthu+Kumaradoss%22">Kathiravan, Muthu Kumaradoss</searchLink><relatesTo>7</relatesTo> (AUTHOR)<i> drmkkathir@gmail.com</i><br /><searchLink fieldCode="AR" term="%22Arockiaraj%2C+Jesu%22">Arockiaraj, Jesu</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> jesuaraj@gmail.com</i>
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  Data: <searchLink fieldCode="JN" term="%22Biotechnology+%26+Applied+Biochemistry%22">Biotechnology & Applied Biochemistry</searchLink>. Apr2025, Vol. 72 Issue 2, p320-339. 20p.
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  Data: <searchLink fieldCode="DE" term="%22Fatty+liver%22">Fatty liver</searchLink><br /><searchLink fieldCode="DE" term="%22Cholecalciferol%22">Cholecalciferol</searchLink><br /><searchLink fieldCode="DE" term="%22Reactive+oxygen+species%22">Reactive oxygen species</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutics%22">Therapeutics</searchLink><br /><searchLink fieldCode="DE" term="%22Inflammatory+mediators%22">Inflammatory mediators</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Liver damage and metabolic dysfunctions, the defining features of non‐alcoholic fatty liver disease (NAFLD), are marked by inflammation, oxidative stress, and excessive hepatic fat accumulation. The current therapeutic approaches for NAFLD are limited, necessitating exploring novel treatment strategies. Dioxopiperidinamide derivatives, particularly DOPA‐33, have shown effective anti‐inflammatory and antioxidant properties, potentially offering therapeutic benefits against NAFLD. This study investigated the combined potential of vitamin D3 (Vit D3) and DOPA‐33 in treating NAFLD. The network pharmacology analysis identified key NAFLD targets modulated by Vit D3 and DOPA‐33, emphasizing their potential mechanisms of action. In NAFLD‐induced zebrafish models, Vit D3 and DOPA‐33 significantly reduced hepatic lipid accumulation, oxidative stress, and apoptosis, demonstrating superior efficacy over individual treatments. The treatment also lowered reactive oxygen species (ROS) levels, decreased liver damage, and enhanced antioxidant defense mechanisms. Moreover, behavioral analyses showed improved locomotion and reduced weight gain in treated zebrafish. Biochemical analyses revealed lower triglycerides (TG) and glucose levels with improved oxidative markers. Furthermore, histological analyses indicated reduced hepatic steatosis and inflammation, with decreased expression of lipogenesis‐related genes and inflammatory mediators. Finally, high‐performance liquid chromatography (HPLC) confirmed a significant reduction in hepatic cholesterol levels, indicating the effectiveness of the combination therapy in addressing key NAFLD‐related dyslipidemias. These findings suggest that Vit D3 + DOPA‐33 targets pathways involved in lipid metabolism, inflammation, and oxidative stress by offering a promising therapeutic approach for NAFLD. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Biotechnology & Applied Biochemistry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1002/bab.2666
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      – Code: eng
        Text: English
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        PageCount: 20
        StartPage: 320
    Subjects:
      – SubjectFull: Fatty liver
        Type: general
      – SubjectFull: Cholecalciferol
        Type: general
      – SubjectFull: Reactive oxygen species
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      – SubjectFull: Therapeutics
        Type: general
      – SubjectFull: Inflammatory mediators
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      – TitleFull: Combined effects of vitamin D3 and dioxopiperidinamide derivative on lipid homeostasis, inflammatory pathways, and redox imbalance in non‐alcoholic fatty liver disease in vivo zebrafish model.
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              Text: Apr2025
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              Y: 2025
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