Sumbalova 2019a MiP2019

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Zuzana Sumbalova
Platelet mitochondrial function, coenzyme Q10, and oxidative stress in patients with chronic kidney diseases.

Link: MiP2019

Sumbalova Z, Gvozdjakova A, Kucharska J, Rausova Z, Vancova O, Kuzmiakova Z, Kubalova M, Ulicna O, Chladekova A, Komlosi M, Szamosova M, Mojto V (2019)

Event: MiP2019

COST Action MitoEAGLE

The mortality rate of patients with chronic kidney diseases (CKD) increases with a decrease in the glomerular filtration rate. Development and progression of CKD are closely linked with noncommunicable diseases (NCDs). Oxidative stress, reduced antioxidant protection and impairment of mitochondrial function in the kidney belong to the molecular mechanisms of CKD origin and development [1,2,3].

We studied the relationships between the glomerular filtration rate (eGFR), mitochondrial function in isolated platelets, concentration of coenzyme Q10 (CoQ10), and oxidative stress in patients with CKD due to NCDs.

58 patients with CKD due to NCDs (cardiovascular diseases, diabetes mellitus and dyslipidemia) and 19 healthy age-matched subjects were enrolled in the study. Mitochondrial respiration in isolated platelets (PLTs) was assessed by O2k-Respirometer (Oroboros Instruments, Austria) at 37°C in respiration medium MiR05 with 20 mM creatine using protocol RP1 [4]. Coenzyme Q10-TOTAL (CoQ10) in isolated PLTs, whole blood and plasma were determined using HPLC method with UV detection. Serum creatinine, uric acid and eGFR were determined by standard laboratory methods. Oxidative stress as thiobarbituric acid reactive substances (TBARS) in plasma was estimated by spectrophotometric method.

Increased concentrations of serum creatinine and uric acid and decreased eGFR in patients with nephropathy allowed division of patients to 4 stages of CKD (according eGFR values). Concentration of CoQ10 in PLTs, whole blood and plasma was decreased and concentration of TBARS increased in the whole group of patients with CKD compared to control group. Respiration of PLTs in the whole group of patients with CKD did not significantly differ from control group. It was slightly higher in patients in the 2nd stage of CKD and significantly lower in patients of 4th stage of CKD when compared to patients in the 2nd stage. In the whole group of patients with CKD we found significant positive correlation between multiple parameters of PLT respiration and CoQ10 in PLTs. Concentration of TBARS negatively correlated with CoQ10 in plasma (r=-0.354, P<0.02).

Our results suggest that lower concentrations of endogenous CoQ10 and oxidative stress could be involved in the development of CKD. We suppose that supportive supplementation with coenzyme Q10 could regenerate mitochondrial oxidative phosphorylation not only in platelets, but also in kidney mitochondria, thereby slowing disease progression and postponing time to chronic dialysis of patients suffering from CKD.


Bioblast editor: Plangger M, Tindle-Solomon L O2k-Network Lab: SK Bratislava Sumbalova Z


Labels: MiParea: Respiration, Patients  Pathology: Other 

Organism: Human  Tissue;cell: Platelet  Preparation: Intact cells 


Coupling state: LEAK, OXPHOS  Pathway: F, N, S, Gp, CIV, NS, ROX  HRR: Oxygraph-2k 


Affiliations

Sumbalová Z(1), Gvozdjáková A(1), Kucharská J(1), Rausová Z(1), Vančová O(1), Kuzmiaková Z(1), Kubalová M(1), Uličná O(1), Chládeková A(2), Komlósi M(2), Mojto V(2)
  1. Comenius Univ Bratislava, Medical Fac, Pharmacobiochemical Lab 3rd Dept Internal Medicine
  2. Comenius Univ Bratislava, Medical Fac, 3rd Dept Internal Medicine; Bratislava, Slovakia. - zuzana.sumbalova@fmed.uniba.sk

References

  1. Granata S, Dalla Gassa A, Tomei P, Lupo A, Zaza G (2015) Mitochondria: a new therapeutic target in chronic kidney disease. Nutr Metab (Lond)12:49.
  2. Gamboa JL, Billings FT, Bojanowski MT, Gilliam LA, Yu C, Roshanravan B, Roberts LJ, Himmelfarb J, Ikizler TA, Brown NJ (2016) Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease. Physiol Rep pii:e12780.
  3. Rivara MB, Yeung CK, Robinson-Cohen C, Phillips BR, Ruzinski J, Rock D, Linke L, Shen DD, Akizler TA, Himmelfarb J (2016) Effect of coenzyme Q10 n biomarkers of oxidative stress and cardiac function in hemodyalysis patients: The CoQ10 biomarker trial. Am J Kidney Dis 69:389-99.
  4. Doerrier C, Sumbalova Z, Krumschnabel G, Hiller E, Gnaiger E (2016) SUIT reference protocol for OXPHOS analysis by high-resolution respirometry. Mitochondr Physiol Network 21.06:1-12.