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Chronic unpredictable mild stress increases serum aldosterone without affecting corticosterone levels and induces hepatic steatosis and renal injury in young adult male rats

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Abstract

Stress is often associated with anxiety and depressive symptoms in adolescents. Stress is associated with components of metabolic syndrome and inflammation. The present study hypothesizes that aldosterone, more than corticosterone, promotes chronic stress-hepatic steatosis and fibrosis, as well as renal inflammation and fibrosis in young adult rats. Thirty-two young adult male Wistar rats of 51 days old were divided into four groups (n = 8 per group): Control (C), chronic unpredictable mild stress (CUMS), control plus vehicle (C plus veh), CUMS plus eplerenone, a selective aldosterone blocker (CUMS plus EP). On postnatal day 51, eplerenone was administered orally through a gastric tube two hours before the start of the stress test. The CUMS paradigm was administered once daily at different times, with no repetition of the stressor sequence for four weeks. Renal inflammation and fibrosis were measured, as well as liver glycogen, triacylglycerol, and fibrosis levels. The serum concentrations of corticosterone, aldosterone, sodium, and creatinine were measured in urine and serum. The CUMS group showed a high level of serum aldosterone without affecting the level of corticosterone, increased urinary sodium, tubular atrophy, glomerular sclerosis, the presence of inflammation, and fibrosis, without affecting creatinine, increased glycogen content, triacylglycerol, and moderate fibrosis in the liver, and treatment with eplerenone prevented the inflammation, fibrosis, glycogen, and triacylglycerol. Our results show that chronic stress-induced aldosterone promotes hepatic steatosis and renal injury more than corticosterone. The prevention by eplerenone supports our hypothesis.

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Funding

This work was supported by the Consejo Nacional de Ciencia y Tecnología (CONACyT; Grant No. 287762 to L. Nicolás-Toledo, Proyecto apoyado por el Fondo Sectorial de Investigación para la Educación), project partially granted by CONACyT – México (ID 322333) during 2022, and a pre-doctoral fellowship (Reg. 266814) from CONACyT to Eliut Pérez Sánchez.

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Pérez-Sánchez Eliut. Contributed to the gathering and analysis of the data. He approved the final version of this manuscript. Corona-Pérez Adriana. Contributed to the gathering and analysis of the data. She approved the final version of this manuscript. Arroyo-Herguera Omar. Contributed to the gathering and analysis of the data, and writing of the manuscript. He approved the final version of this manuscript. Soto-Rodríguez Ida. Contributed to writing the manuscript and did a critical revision of the manuscript. He approved the final version of this manuscript. Senobia Rosalía Cruz-Lumbreras. Contributed to the gathering and analysis of the data. She approved the final version of this manuscript. Rodríguez-Antolín Jorge. Contributed to writing the manuscript and did a critical revision of the manuscript. He approved the final version of this manuscript. Cuevas Romero Estela. Contributed to the gathering and analysis of the data, and writing of the manuscript. She approved the final version of this manuscript. Nicolás-Toledo Leticia. Contributed to the analysis of the data, writing of the manuscript, and funding of the study. She approved the final version of this manuscript.

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Correspondence to Leticia Nicolás-Toledo.

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The authors have declared that there is no conflict of interest.

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Pérez Sánchez, E., Corona-Pérez, A., Arroyo-Helguera, O. et al. Chronic unpredictable mild stress increases serum aldosterone without affecting corticosterone levels and induces hepatic steatosis and renal injury in young adult male rats. J Mol Histol (2024). https://doi.org/10.1007/s10735-024-10188-3

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  • DOI: https://doi.org/10.1007/s10735-024-10188-3

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