Romanian Society of Pharmaceutical Sciences

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DECREASED RESPIRATORY FUNCTION IN LIVER MITOCHONDRIA ISOLATED FROM HEALTY OLD RATS

IOANA MIHAELA CITU1#, DORINA CORICOVAC2#, VIORICA KERTI1, OANA DUICU1, ANDREEA PRIVISTIRESCU1, SIMONA ARDELEAN3*, DANINA MUNTEAN1, CRISTINA DEHELEAN2

1.Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy Timişoara, 2, Eftimie Murgu Sq., 300041, Timișoara, Romania
2.Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy Timişoara, 2, Eftimie Murgu Sq., 300041, Timișoara, Romania
3.Faculty of Pharmacy, “Vasile Goldis” University of Medicine and Pharmacy Arad, Romania

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Mitochondrion dysfunction has been constantly associated with ageing yet a significant variation across animal species and investigated tissues has been reported. We have previously demonstrated that healthy ageing is associated with impairment in heart mitochondria function. The purpose of the present study was to compare mitochondrial respiratory function in liver mitochondria of from old (20-24 months) vs. adult (4-6 months) healthy rats. Mitochondria were isolated by differential centrifugations and the respiratory function was assessed at 37ºC using a Clark-type oxygen electrode in the presence of NAD+-linked substrates (glutamate/malate) and a FAD-linked substrate (succinate in the presence of rotenone), respectively. Basal (State 2) and ADP-stimulated (State 3) respiratory rates were measured and expressed as natoms O2/min/mg of mitochondrial protein. The respiratory control ratio (RCR) was calculated as the ratio of State 3 and State 2 respiratory rates. The intactness of mitochondria was verified by adding exogenous cytochrome c. Our data showed a significant decline in both State 2 and 3 respiratory rates in mitochondria isolated from old as compared to adult rodents when using either NAD+ (20.68 ± 2.43 vs. 24.46 ± 2.38, p < 0.001; 101.11 ± 5.40 vs. 121.60 ± 17.74, p < 0.001, respectively) or FAD+ (33.55 ± 3.28 vs. 42.75 ± 1.83, p < 0.0001; 123.92 ± 5.02 vs. 140.69 ± 15.37, p < 0.001, respectively) linked substrates. In conclusion, the impairment of respiratory parameters in the senescent group supports the hypothesis that a decrease of respiratory function in liver mitochondria occurs during healthy ageing.