Ukr.Biochem.J. 2018; Volume 90, Issue 1, Jan-Feb, pp. 42-47

doi: https://doi.org/10.15407/ubj90.01.042

Activity of the mitochondrial isoenzymes of endogenous aldehydes catabolism under the conditions of acetaminophen-induced hepatitis

O. M. Voloshchuk, G. P. Kopylchuk, Y. I. Mishyna

Yuriy Fedkovych Chernivtsi National University, Institute of Biology, Chemistry and Natural Resources, Ukraine;
e-mail: o.voloschuk@chnu.edu.ua

The research deals with the determination of the activity of aldehyde dehydrogenase (EC 1.2.1.3), aldehyde reductase (EC 1.1.1.21) as well as the content of TBA reactive substances and protein carbonyl derivates in the rat liver  cytosolic fraction under the conditions of acetaminophen-induced hepatitis and protein deficiency. The most pronounced decrease in the activity of enzymes utilizing endogenous aldehydes is observed in the liver cytosolic fraction of animals with toxic liver injury maintained under the conditions of alimentary protein deficiency. Meanwhile, the accumulation of TBA reactive substances and protein carbonyl-derivates in the liver cytosolic fraction of animals of this experimental group was established. The accumulation of aldehyde products of lipid and protein oxidative damage on the background of the reduction in the activity of enzymes providing aldehyde catabolism may be considered as a possible mechanism underlying hepatocyte dysfunction under the conditions of toxic damage in protein-deficient animals.

Keywords: , , , , , ,


References:

  1. Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell. 2012 Mar 16;148(6):1145-59. PubMed, PubMedCentral, CrossRef
  2. Voelker DR. Genetic and biochemical analysis of non-vesicular lipid traffic. Annu Rev Biochem. 2009;78:827-56. PubMed, CrossRef
  3. De Stefani D, Raffaello A, Teardo E, Szabò I, Rizzuto R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature. 2011 Jun 19;476(7360):336-40.  PubMed, PubMedCentral, CrossRef
  4. Hamanaka RB, Chandel NS. Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci. 2010 Sep;35(9):505-13. PubMed, PubMedCentral, CrossRef
  5. Cadenas E. Mitochondrial free radical production and cell signaling. Mol Aspects Med. 2004 Feb-Apr;25(1-2):17-26. PubMed,CrossRef
  6.  Whaley-Connell A, McCullough PA, Sowers JR. The role of oxidative stress in the metabolic syndrome. Rev Cardiovasc Med. 2011;12(1):21-9. PubMed
  7. O’Brien PJ, Siraki AG, Shangari N. Aldehyde sources, metabolism, molecular toxicity mechanisms, and possible effects on human health. Crit Rev Toxicol. 2005 Aug;35(7):609-62. PubMed, CrossRef
  8. Barski OA, Tipparaju SM, Bhatnagar A. The aldo-keto reductase superfamily and its role in drug metabolism and detoxification. Drug Metab Rev. 2008;40(4):553-624.  PubMed, PubMedCentral, CrossRef
  9. Kopylchuk GP, Voloshchuk OM. Peculiarities of the free radical processes in rat liver mitochondria under toxic hepatitis on the background of alimentary protein deficiency. Ukr Biochem J. 2016 Mar-Apr;88(2):66-72. PubMed, CrossRef
  10. Voloshchuk ON, Kopylchuk GP. The ratio of ubiquinon redox forms in the liver mitochondria under toxic hepatitis induced on the background of alimentary protein deficiency. Probl Nutr. 2015;84(5):82-7. (In Russian).
  11. Kuvandik G, Duru M, Nacar A, Yonden Z, Helvaci R, Koc A, Kozlu T, Kaya H, Sogüt S. Effects of erdosteine on acetaminophen-induced hepatotoxicity in rats. Toxicol Pathol. 2008 Jul;36(5):714-9. PubMed, CrossRef
  12. Kislova OV, Vinogradova EG, Pkhakadze GA. Comparative characteristics of membrane forms of aldehyde dehydrogenase. Ukr Biokhim Zhurn. 1995 Nov-Dec;67(6):38-45. (In Russian). PubMed
  13. Fomina EV, Davydov VV. Aldehyde reductase activity in the liver of rats of various age at immobilization stress. Probl Staren Dolgolet. 2004; 13(4):510-16. (In Russian).
  14. Rodrigues T, de França LP, Kawai C, de Faria PA, Mugnol KC, Braga FM, Tersariol IL, Smaili SS, Nantes IL. Protective role of mitochondrial unsaturated lipids on the preservation of the apoptotic ability of cytochrome C exposed to singlet oxygen. J Biol Chem. 2007 Aug 31;282(35):25577-87.  PubMed, CrossRef
  15. Parihar MS, Pandit MK. Free radical induced increase in protein carbonyl is attenuated by low dose of adenosine in hippocampus and mid brain: implication in neurodegenerative disorders. Gen Physiol Biophys. 2003 Mar;22(1):29-39. PubMed
  16. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265-75. PubMed
  17. Marchitti SA, Brocker C, Stagos D, Vasiliou V. Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily. Expert Opin Drug Metab Toxicol. 2008 Jun;4(6):697-720.  PubMed, PubMedCentral, CrossRef
  18. Andringa KK, Bajt ML, Jaeschke H, Bailey SM. Mitochondrial protein thiol modifications in acetaminophen hepatotoxicity: effect on HMG-CoA synthase. Toxicol Lett. 2008 Apr 1;177(3):188-97.  PubMed, PubMedCentral, CrossRef
  19. Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014;2014:360438.  PubMed, PubMedCentral, CrossRef
  20. Krysiuk IP, Knaub AJ, Shandrenko SG. Comparison of bioactive aldehydes modifying action on human albumin. Ukr Biochem J. 2014 Mar-Apr;86(2):68-78. (In Ukrainian). PubMed, CrossRef
  21. 21. Singh S, Brocker C, Koppaka V, Chen Y, Jackson BC, Matsumoto A, Thompson DC, Vasiliou V. Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress. Free Radic Biol Med. 2013 Mar;56:89-101. PubMed, PubMedCentral, CrossRef
  22. Kurahashi T, Kwon M, Homma T, Saito Y, Lee J, Takahashi M, Yamada K, Miyata S, Fujii J. Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals. Biochem Biophys Res Commun. 2014 Sep 12;452(1):136-41.  PubMed, CrossRef

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