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The pressure-induced natriuresis (PN) refers to increase in urinary sodium excretion due to an elevation in renal perfusion pressure, thereby reducing blood pressure (BP). Impairment of this mechanism leads to adaptation, requiring higher BP to maintain natriuresis. Salt sensitivity is defined as an increase in BP following salt intake, activating proinflammatory and prooxidant metabolic cascades. In this context, coenzyme Q10 (CoQ10) is a lipid-soluble and biologically active quinone with a high antioxidant capacity due to the coexistence of its redox forms. These forms allow it to control cellular redox status by regulating the generation of reactive oxygen species (ROS), protecting the cell from free radical. Furthermore, CoQ10 exhibits anti-inflammatory action and the ability to inhibit proinflammatory genes. We hypothesize that dietary supplementation with CoQ10 has a cardio-renoprotective effect in rats with normal renal function (FRN) and moderate renal insufficiency (UNX) after salt overload through antioxidant and anti-inflammatory mechanisms.
Two groups of Wistar rats (150 g) were used (n=20 each), subjected to surgeries: uninephrectomy (UNX) to generate renal damage models. Normal renal function (NRF) group did not undergo surgery. After adaptation period (0 days for NRF and 30 days for UNX), each group was subdivided into 4: G1=(NNaD) Normal sodium diet: NaCl 0.2%, G2=(HNaD): NaCl 4%, G3=CoQ10 (200mg/kg/day) + NaCl 4%, and G4=CoQ10. BP was recorded using tail cuff technique, and baseline weight was measured at 45-and 100-days post-treatment. At the ends, proteinuria and creatinine clearance were determined. We measured ROS in whole blood, while in renal mitochondria, total glutathione content (GSHMt), superoxide dismutase activity (SODMt), and mitochondrial complexes (I-III) activity. Additionally, glomerular fibrosis score was determined. To salt sensitivity evaluation, animals from G1 and G4 (both NRF and UNX) underwent a 7-day sodium balance study, with a diet switch incorporating 4% NaCl while maintaining CoQ10 supplementation. Increases in BP induced by NaCl was then determined.
In both groups, there was an increase in blood pressure (BP) in animals HNaD compared to HNaD+CoQ10. This was not associated with weight changes. This effect persisted until Day 100. The prevention of BP increase was associated with an 89% proteinuria reduction in HNaD. In UNX, CoQ10-mediated effects were also observed in creatinine clearance. While all groups increased clearance G3 did not show hyperfiltration effects (Clearance mL/min in G3= 1.87-1.51 at baseline and Day 100, respectively). These pathophysiological changes observed in G3 were associated with a lower incidence of Bowman's basement membrane thickening, adhesions, and glomerular folding, implying less renal fibrosis in these animals. After sodium balance study, prevention PN deterioration mechanism was observed during CoQ10 supplementation (Figure 1). In the evaluation of redox response, we observed that HNaD had elevated ROS formation, and CoQ10 treatment decreased it. We also observed that the decrease in GSHMt in HNaD was prevented with CoQ10. In this regard, an improvement in mitochondrial activity complexes I-III was also observed in NRF animals treated with CoQ10, and there was no difference in UNX (Table 1).
Dietary supplementation with CoQ10 during high-sodium diet in chronic kidney disease (CKD) prevented the increase in systemic and renal oxidative stress, preserving the pressure-induced natriuresis mechanism, reducing blood pressure, proteinuria, and the impairment of target organs, such as the kidney.