Hyponatremia and Oxidative Stress.

Benedetta Fibbi,Cecilia Anceschi,Laura Naldi,Giada Marroncini,Alessandro Peri

doi:10.3390/antiox10111768

Abstract

Hyponatremia, i.e., the presence of a serum sodium concentration ([Na+]) < 136 mEq/L, is the most frequent electrolyte imbalance in the elderly and in hospitalized patients. Symptoms of acute hyponatremia, whose main target is the central nervous system, are explained by the “osmotic theory” and the neuronal swelling secondary to decreased extracellular osmolality, which determines cerebral oedema. Following the description of neurological and systemic manifestations even in mild and chronic hyponatremia, in the last decade reduced extracellular [Na+] was associated with detrimental effects on cellular homeostasis independently of hypoosmolality. Most of these alterations appeared to be elicited by oxidative stress. In this review, we focus on the role of oxidative stress on both osmolality-dependent and -independent impairment of cell and tissue functions observed in hyponatremic conditions. Furthermore, basic and clinical research suggested that oxidative stress appears to be a common denominator of the degenerative processes related to aging, cancer progression, and hyponatremia. Of note, low [Na+] is able to exacerbate multiple manifestations of senescence and to decrease progression-free and overall survival in oncologic patients.

Highlights

Hyponatremia, defined as a serum sodium concentration ([Na+ ]) < 136 mEq/L, is the most frequent electrolyte disorder encountered in clinical practice, especially in hospitalized patients and in the elderly [1]
We showed that reduced extracellular [Na+ ] disrupts gene expression, proliferation, migration, and cytokine production in human mesenchymal stromal cells [109], which are precursors of mesodermal cell types exhibiting different degrees of stemness [110]
For the first time, that the reduction of extracellular [Na+ ] is able to alter the homeostasis of different human cancer cell lines, affecting cell functions distinctive of a more malignant behavior able to increase cell tumorigenicity [126]

Summary

Introduction

Since hyponatremia is associated with increased morbidity and mortality even in mildly affected patients, it represents an economic burden in terms of hospitalization and health care costs [2,3,4,5,6,7,8]. From this view, a prompt and appropriate correction of this electrolytic imbalance is critical to prevent short- and long-term complications. The comprehension of molecular mechanisms involved in the pathogenesis of symptoms related to hyponatremia might help to raise the awareness about the importance of correcting even chronic and mild reductions of [Na+ ]

Hyponatremia and Health

Osmotically-Induced Oxidative Stress

Non Osmotically-Induced Oxidative Stress

Findings

Conclusions