The protective role of Astaxanthin against the central and peripheral detrimental effects for chronic administration of sweeteners in a rat model: Involvement of multiple signaling axes.
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| Format: | Artículo científico |
| Language: | en |
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The Journal of nutritional biochemistry
2026
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| author | Hamdan, Ahmed M E Abu-Elfotuh, Karema Alshaman, Reem Salem, Hoda A Hamdan, Amira M Alaisayi, Khulud H A Alharthi, Sawsan A S Aljehani, Raghad F S Alsharif, Fai I M Abalhassan, Abdullah K M Albugami, Abdulmajeed S Sirag, Nizar Abdelsalam, Moustafa H Panneerselvam, Chellasamy Mani, Vasudevan Abdel-Maksoud, Mohamed S Alanazi, Fawaz E Masoud, Rehab Ali Elsayed Darwish, Alshaymaa Gowifel, Ayah M H |
| author_facet | Hamdan, Ahmed M E Abu-Elfotuh, Karema Alshaman, Reem Salem, Hoda A Hamdan, Amira M Alaisayi, Khulud H A Alharthi, Sawsan A S Aljehani, Raghad F S Alsharif, Fai I M Abalhassan, Abdullah K M Albugami, Abdulmajeed S Sirag, Nizar Abdelsalam, Moustafa H Panneerselvam, Chellasamy Mani, Vasudevan Abdel-Maksoud, Mohamed S Alanazi, Fawaz E Masoud, Rehab Ali Elsayed Darwish, Alshaymaa Gowifel, Ayah M H Hamdan, Ahmed M E Abu-Elfotuh, Karema Alshaman, Reem Salem, Hoda A Hamdan, Amira M Alaisayi, Khulud H A Alharthi, Sawsan A S Aljehani, Raghad F S Alsharif, Fai I M Abalhassan, Abdullah K M Albugami, Abdulmajeed S Sirag, Nizar Abdelsalam, Moustafa H Panneerselvam, Chellasamy Mani, Vasudevan Abdel-Maksoud, Mohamed S Alanazi, Fawaz E Masoud, Rehab Ali Elsayed Darwish, Alshaymaa Gowifel, Ayah M H |
| collection | PubMed - marine biology |
| contents | The protective role of Astaxanthin against the central and peripheral detrimental effects for chronic administration of sweeteners in a rat model: Involvement of multiple signaling axes. Hamdan, Ahmed M E Abu-Elfotuh, Karema Alshaman, Reem Salem, Hoda A Hamdan, Amira M Alaisayi, Khulud H A Alharthi, Sawsan A S Aljehani, Raghad F S Alsharif, Fai I M Abalhassan, Abdullah K M Albugami, Abdulmajeed S Sirag, Nizar Abdelsalam, Moustafa H Panneerselvam, Chellasamy Mani, Vasudevan Abdel-Maksoud, Mohamed S Alanazi, Fawaz E Masoud, Rehab Ali Elsayed Darwish, Alshaymaa Gowifel, Ayah M H Animals Xanthophylls Male Liver Signal Transduction Oxidative Stress Rats Sweetening Agents Brain Stevia Heart Antioxidants Lipid Metabolism Rats, Wistar Apoptosis Obesity and diabetes are escalating worldwide health concerns, prompting the use of non-caloric sweeteners such as aspartame and stevia as substitutes for sucrose; however, their long-term physiological and behavioral consequences remain incompletely understood. This work presents a comparative experimental study examining the long-term effects of sucrose, aspartame, and stevia intake on liver, heart, and brain functions in rats, while exploring the capacity of astaxanthin (ASTX) to attenuate the resulting tissue impairments. Seven rat groups-including control, sucrose, aspartame, stevia, and each sweetener combined with ASTX-were treated for 8 weeks to compare the organ-specific toxicity of the sweeteners and assess the protective effects of ASTX. Comprehensive evaluations of liver, heart, and brain were conducted using biochemical, behavioral, and histopathological analyses. All three sweeteners induced hyperglycemia, disrupted lipid metabolism (triglycerides, LDL, HDL), and increased oxidative stress (MDA), suppressing Nrf2/HO-1 antioxidant pathway and activating TLR4/NF-κB-mediated inflammation, leading to apoptosis. Biomarkers revealed liver dysfunction (ALT, AST, ALP), cardiac injury (troponin I, CK-MB, MEF2), and cognitive impairment (amyloid-beta, tau, BDNF), alongside altered monoamine neurotransmitters and Wnt3a/GSK-3β/β-catenin dysregulation. Bax/Bcl-2 ratio indicated enhanced apoptosis, with aspartame exerting the highest toxicity and stevia the least. While ASTX effectively alleviated these biochemical, histological, and functional changes. These findings suggest that aspartame has the strongest negative impact on liver, heart, and brain health, while stevia has the least, and that ASTX may serve as a potential protective agent against these harmful impacts. |
| format | Artículo científico |
| id | pubmed_41688030 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | The Journal of nutritional biochemistry |
| record_format | pubmed |
| spellingShingle | The protective role of Astaxanthin against the central and peripheral detrimental effects for chronic administration of sweeteners in a rat model: Involvement of multiple signaling axes. Hamdan, Ahmed M E Abu-Elfotuh, Karema Alshaman, Reem Salem, Hoda A Hamdan, Amira M Alaisayi, Khulud H A Alharthi, Sawsan A S Aljehani, Raghad F S Alsharif, Fai I M Abalhassan, Abdullah K M Albugami, Abdulmajeed S Sirag, Nizar Abdelsalam, Moustafa H Panneerselvam, Chellasamy Mani, Vasudevan Abdel-Maksoud, Mohamed S Alanazi, Fawaz E Masoud, Rehab Ali Elsayed Darwish, Alshaymaa Gowifel, Ayah M H Animals Xanthophylls Male Liver Signal Transduction Oxidative Stress Rats Sweetening Agents Brain Stevia Heart Antioxidants Lipid Metabolism Rats, Wistar Apoptosis The protective role of Astaxanthin against the central and peripheral detrimental effects for chronic administration of sweeteners in a rat model: Involvement of multiple signaling axes. Hamdan, Ahmed M E Abu-Elfotuh, Karema Alshaman, Reem Salem, Hoda A Hamdan, Amira M Alaisayi, Khulud H A Alharthi, Sawsan A S Aljehani, Raghad F S Alsharif, Fai I M Abalhassan, Abdullah K M Albugami, Abdulmajeed S Sirag, Nizar Abdelsalam, Moustafa H Panneerselvam, Chellasamy Mani, Vasudevan Abdel-Maksoud, Mohamed S Alanazi, Fawaz E Masoud, Rehab Ali Elsayed Darwish, Alshaymaa Gowifel, Ayah M H Animals Xanthophylls Male Liver Signal Transduction Oxidative Stress Rats Sweetening Agents Brain Stevia Heart Antioxidants Lipid Metabolism Rats, Wistar Apoptosis Obesity and diabetes are escalating worldwide health concerns, prompting the use of non-caloric sweeteners such as aspartame and stevia as substitutes for sucrose; however, their long-term physiological and behavioral consequences remain incompletely understood. This work presents a comparative experimental study examining the long-term effects of sucrose, aspartame, and stevia intake on liver, heart, and brain functions in rats, while exploring the capacity of astaxanthin (ASTX) to attenuate the resulting tissue impairments. Seven rat groups-including control, sucrose, aspartame, stevia, and each sweetener combined with ASTX-were treated for 8 weeks to compare the organ-specific toxicity of the sweeteners and assess the protective effects of ASTX. Comprehensive evaluations of liver, heart, and brain were conducted using biochemical, behavioral, and histopathological analyses. All three sweeteners induced hyperglycemia, disrupted lipid metabolism (triglycerides, LDL, HDL), and increased oxidative stress (MDA), suppressing Nrf2/HO-1 antioxidant pathway and activating TLR4/NF-κB-mediated inflammation, leading to apoptosis. Biomarkers revealed liver dysfunction (ALT, AST, ALP), cardiac injury (troponin I, CK-MB, MEF2), and cognitive impairment (amyloid-beta, tau, BDNF), alongside altered monoamine neurotransmitters and Wnt3a/GSK-3β/β-catenin dysregulation. Bax/Bcl-2 ratio indicated enhanced apoptosis, with aspartame exerting the highest toxicity and stevia the least. While ASTX effectively alleviated these biochemical, histological, and functional changes. These findings suggest that aspartame has the strongest negative impact on liver, heart, and brain health, while stevia has the least, and that ASTX may serve as a potential protective agent against these harmful impacts. |
| title | The protective role of Astaxanthin against the central and peripheral detrimental effects for chronic administration of sweeteners in a rat model: Involvement of multiple signaling axes. |
| topic | Animals Xanthophylls Male Liver Signal Transduction Oxidative Stress Rats Sweetening Agents Brain Stevia Heart Antioxidants Lipid Metabolism Rats, Wistar Apoptosis |
| url | https://pubmed.ncbi.nlm.nih.gov/41688030/ |