Abstract: Background/Objectives: The prevalence of cardiovascular-kidney-metabolic (CKM) syndrome
is increasing rapidly, and cardiovascular complications pose significant risks in individuals
with kidney disease and metabolic dysfunction. Understanding the mechanisms of CKM disorders
is crucial, as is the discovery of novel preventive treatments. This study aimed to examine the
therapeutic effects of a specially formulated nitric oxide-enhancing food additive in a mouse model
of CKM syndrome induced by unilateral nephrectomy (UNX) in combination with chronicWestern
diet (WD) feeding. Methods: C57BL/6J mice underwent UNX and were fed a WD high in salt, sugar,
and fat for 12 weeks, compared to sham-operated mice on standard chow. One group of UNX+WD
mice received Flexovital (FLX), a food additive containing extracts of Rhodiola rosea and beetroot, and
the amino acids L-arginine and L-citrulline. CKM parameters were assessed both in vivo and ex vivo
alongside histological and biochemical analyses. Results: The UNX+WD mice showed an increase in
body fat mass, the fat/lean mass ratio, and adipocyte area, of which most were significantly reduced
by FLX. Elevated fasting glucose levels were also reduced by FLX, which tended towards improving
glucose clearance. Elevated arterial blood pressure and endothelial dysfunction in UNX+WD mice
were significantly reduced by FLX. FLX improved GFR and reduced glomerular and tubular injuries
in UNX+WD mice. Additionally, FLX increased the P/O ratios of oxidative phosphorylation in the
isolated renal mitochondria of UNX+WD mice. Conclusions: In this model of CKM syndrome, FLX
effectively prevented the onset and progression of CKM dysfunctions induced by UNX+WD, as
well as the associated organ injuries. These promising results highlight the need for validation in
upcoming human trials.
Body composition analysis, small animal DXA, InAlyzer
