The effects of low-sodium salt substitute on multiple organ pathology markers in the experimental “dietary-related” aging model based on D-galactose highlight the significant role of correcting elemental balance in salt-dependent arterial hypertension and aging

Background. Low-sodium salt substitutes (LSSS) are widely used in the dietary management of patients with arterial hypertension.
Objective: To investigate the effects of LSSS in white rats using a model of accelerated “dietary-related” aging induced by D-galactose combined with palm oil, dietary L-methionine, sodium chloride in drinking water, and ferrous sulfate.
Material and methods. The study included 30 male Wistar rats weighing 300–500 g. Model induction was performed until Day 13; after that, all animals with reproduced pathology were switched to a standard diet, and a subset of these animals received LSSS therapy until Day 54 of the experiment. On Days 0, 13, and 54, sixty parameters were assessed, including the results of complete blood count, serum biochemistry, and neurological testing.
Results. The model reproduced a complex of disorders, including altered biomarkers of multiple organ pathology, hematopoietic dysfunction, and deterioration of neurological status. The use of LSSS from Day 13 to Day 54 mitigated the progression of accelerated multiple organ aging. In particular, model induction increased serum creatinine (intact: 35.67±1.21 μmol/l; model, Day 54: 39.17±1.47 μmol/l; p=0.000628) with a significant reduction in glomerular filtration rate (GFR) (intact: 167.41±7.26 ml/min/1.73 m2 ; model, Day 54: 153.4±6.32 ml/min/1.73 m2 , p=0.002646). The LSSS promoted the normalization of serum creatinine (model, Day 54: 39.17±1.47 μmol/l; LSSS: 33.33±1.86 μmol/l; p=0.000628) and GFR (model, Day 54: 153.4±6.32 ml/min/1.73 m2 ; LSSS: 181.1±12.27 mL/min/1.73 m2 ; p=0.002646), bringing these parameters toward values typical of intact animals. Furthermore, LSSS contributed to the normalization of iron and electrolyte metabolism. It restored transferrin saturation (model, Day 54: 69.88±11.79%; LSSS: 46.7±10.8%; p=0.053335), with levels comparable to those of intact animals. Improvements were also noted in the levels of magnesium (model, Day 54: 1.12±0.01 mmol/l; LSSS: 1.22±0.14 mmol/l; p=0.004019), sodium (model, Day 54: 141.42±1.3 mmol/l; LSSS: 138.13±1.61 mmol/l; p=0.069579), and potassium (model, Day 54: 7.29±0.05 mmol/l; LSSS: 8.06±1.72 mmol/l). LSSS also reduced liver damage induced by the model, alleviated chronic inflammation, and normalized hematopoiesis (restoration of immature reticulocyte fractions, medium- and high-fluorescence fractions). Neurological evaluation using the open field and Porsolt tests demonstrated that model-induced neurological impairments were effectively mitigated by LSSS therapy.
Conclusion. Standardized LSSS administration promotes attenuation of aging-related pathophysiology in the studied experimental model.

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