MELATONIN SELECTIVELY ATTENUATES HISTOPATHOLOGICAL ALTERATIONS IN A HUMANIZED MOUSE MODEL OF SICKLE CELL ANEMIA
- 1Universidade Estadual Paulista (UNESP), São José do Rio Preto, SP, Brazil
- 2Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
- 3Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS, Brazil
Abstract
Introduction: Sickle cell anemia (SCA) is characterized by chronic hemolysis, inflammation, oxidative stress, and recurrent vaso-occlusive events that promote progressive damage to multiple organs. Melatonin (MEL) exhibits antioxidant, anti-inflammatory, and cytoprotective properties that may limit chronic tissue injury associated with SCA. This study evaluated the effects of prolonged MEL supplementation on histopathological alterations in target organs of humanized SCA mice. Methods: Humanized SCA mice were generated by transplantation of bone marrow mononuclear cells from Berkeley SS or SA donors into lethally irradiated recipients (CEUA/UNICAMP, protocol 5955-1/2022). Animals were allocated into SA controls, untreated SS, and SS treated with MEL (10 mg/kg/day, orally, for 60-days, n=5/group). Histopathological evaluation of spleen, liver, and kidney sections was performed using hematoxylin-eosin and Masson's trichrome staining. Tissue organization, perivascular erythrocyte accumulation, fibrosis, megakaryocyte infiltration, hemosiderin deposition, necrosis, and hepatic hyperplasia were assessed using a blinded three-point semiquantitative scoring system. Group comparisons were performed using the Kruskal-Wallis test followed by Dunn's multiple-comparison test with Holm correction. Results: MEL selectively reduced histopathological lesions in humanized SCA mice. In the spleen, MEL significantly decreased fibrosis (p=0.005), megakaryocyte infiltration (p=0.011), and hemosiderin deposition (p=0.013) compared with untreated SS mice, whereas no significant effect was observed on tissue organization or perivascular erythrocyte accumulation. In the liver, MEL significantly reduced hyperplasia (p=0.013) and hemosiderin deposition (p=0.044), while perivascular erythrocyte accumulation remained unchanged. Renal architecture was preserved in all groups; however, MEL significantly reduced perivascular erythrocyte accumulation compared with untreated SS animals (p=0.002). No significant differences were detected for parameters that showed no variability among experimental groups. Conclusion: Prolonged melatonin supplementation selectively attenuated chronic histopathological alterations in target organs of humanized SCA mice, with the most consistent effects observed in splenic fibrosis, megakaryocyte infiltration and hemosiderin deposition, hepatic hyperplasia and hemosiderin deposition, and renal vascular congestion. These findings reinforce the role of oxidative stress in chronic organ injury and support melatonin as a promising adjunctive strategy to mitigate tissue damage associated with SCA.
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BibTeX
@article{torres2026melatonin,
title = {{MELATONIN SELECTIVELY ATTENUATES HISTOPATHOLOGICAL ALTERATIONS IN A HUMANIZED MOUSE MODEL OF SICKLE CELL ANEMIA}},
author = {Flaviene Felix TORRES and Victoria Simões BERNARDO and Bárbara Braga Vieira MARQUES and Lucas Nathan De Souza NUNES and Daniela Cagnoto NORONHA and Mayara Cristina Moreira SILVA and Fernando Ferreira COSTA and Marcus Alexandre Finzi CORAT and Lucas GAZARINI and Danilo Grunig Humberto DA SILVA},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.106672},
url = {https://doi.org/10.1016/j.htct.2026.106672},
note = {CC BY},
}
RIS
TY - JOUR
TI - MELATONIN SELECTIVELY ATTENUATES HISTOPATHOLOGICAL ALTERATIONS IN A HUMANIZED MOUSE MODEL OF SICKLE CELL ANEMIA
AU - Flaviene Felix TORRES
AU - Victoria Simões BERNARDO
AU - Bárbara Braga Vieira MARQUES
AU - Lucas Nathan De Souza NUNES
AU - Daniela Cagnoto NORONHA
AU - Mayara Cristina Moreira SILVA
AU - Fernando Ferreira COSTA
AU - Marcus Alexandre Finzi CORAT
AU - Lucas GAZARINI
AU - Danilo Grunig Humberto DA SILVA
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.106672
UR - https://doi.org/10.1016/j.htct.2026.106672
AB - Introduction: Sickle cell anemia (SCA) is characterized by chronic hemolysis, inflammation, oxidative stress, and recurrent vaso-occlusive events that promote progressive damage to multiple organs. Melatonin (MEL) exhibits antioxidant, anti-inflammatory, and cytoprotective properties that may limit chronic tissue injury associated with SCA. This study evaluated the effects of prolonged MEL supplementation on histopathological alterations in target organs of humanized SCA mice. Methods: Humanized SCA mice were generated by transplantation of bone marrow mononuclear cells from Berkeley SS or SA donors into lethally irradiated recipients (CEUA/UNICAMP, protocol 5955-1/2022). Animals were allocated into SA controls, untreated SS, and SS treated with MEL (10 mg/kg/day, orally, for 60-days, n=5/group). Histopathological evaluation of spleen, liver, and kidney sections was performed using hematoxylin-eosin and Masson's trichrome staining. Tissue organization, perivascular erythrocyte accumulation, fibrosis, megakaryocyte infiltration, hemosiderin deposition, necrosis, and hepatic hyperplasia were assessed using a blinded three-point semiquantitative scoring system. Group comparisons were performed using the Kruskal-Wallis test followed by Dunn's multiple-comparison test with Holm correction. Results: MEL selectively reduced histopathological lesions in humanized SCA mice. In the spleen, MEL significantly decreased fibrosis (p=0.005), megakaryocyte infiltration (p=0.011), and hemosiderin deposition (p=0.013) compared with untreated SS mice, whereas no significant effect was observed on tissue organization or perivascular erythrocyte accumulation. In the liver, MEL significantly reduced hyperplasia (p=0.013) and hemosiderin deposition (p=0.044), while perivascular erythrocyte accumulation remained unchanged. Renal architecture was preserved in all groups; however, MEL significantly reduced perivascular erythrocyte accumulation compared with untreated SS animals (p=0.002). No significant differences were detected for parameters that showed no variability among experimental groups. Conclusion: Prolonged melatonin supplementation selectively attenuated chronic histopathological alterations in target organs of humanized SCA mice, with the most consistent effects observed in splenic fibrosis, megakaryocyte infiltration and hemosiderin deposition, hepatic hyperplasia and hemosiderin deposition, and renal vascular congestion. These findings reinforce the role of oxidative stress in chronic organ injury and support melatonin as a promising adjunctive strategy to mitigate tissue damage associated with SCA.
SN - 2531-1379
SN - 2531-1387
ER -