THE EFFECTS OF THE SALVIFOLIN ON THE CONDITION OF MITOCHONDRIAL PORE OF RAT HEART WITH ALLOXAN-INDUCED DIABETES

DOI: https://doi.org/10.29296/25877313-2018-02-06
Download full text PDF
Issue: 
2
Year: 
2018

M.I. Asrarov Dr.Sc. (Biol.), Professor, Head of Laboratory of Molecular Biophysics, A.S. Sadykov Institute of the Bioorganic Chemistry of the Academy of Sciences of the Republic of Uzbekistan (Tashkent) E-mail: asrarov54@mail.ru A.V. Shkinev Ph.D. (Biol.), Senior Research Scientist, A.S. Sadykov Institute of the Bioorganic Chemistry of the Academy of Sciences of the Republic of Uzbekistan (Tashkent) M.K. Pozilov Junior Research Scientist, A.S. Sadykov Institute of the Bioorganic Chemistry of the Academy of Sciences of the Republic of Uzbekistan (Tashkent) E-mail: mamurjon2281@mail.ru N.A. Ergashev Ph.D. (Biol.), Senior Research Scientist, A.S. Sadykov Institute of the Bioorganic Chemistry of the Academy of Sciences of the Republic of Uzbekistan (Tashkent) E-mail: nurali7973@mail.ru K.A. Eshbakova Ph.D. (Chem.), Senior Research Scientist, A.S. Sadykov Institute of the Bioorganic Chemistry of the Academy of Sciences of the Republic of Uzbekistan (Tashkent)

In vitro and in vivo experiments on the effects of the clerodane diterpenoid salvifolin, isolated from Pulicaria salviifolia, on rat heart mitochondrial pore (mPTP) with alloxan-induced diabetes (ED) were investigated. The experiments showed the inhibitory effect of salvifolin on the mPTP of rat hearts, similar to cyclosporine A. It was found, that the speed of Ca2+-dependent opening of mPTP in rat heart with ED is higher than rat heart mitochondria of the control group, which indicates mPTP’s dysfunction of rat heart with ED. In these conditions, pharmacotherapy for 8 days with salvifoline at a dose of 3.5 mg / kg body weight, as well as insulin at a dose of 0.5 ug/kg body weight, transfers to mPTP to the closed state. The stabi-lizing effect of salvifolin on the mitochondrial membrane of rat heart with ED is probably related to the inhibition of mPTP. The obtained results show that, with ED mPTP of the rat heart functions in a state of high conductivity, which may be one of the mechanisms of the development of diabetic cardiomyopathy, which leads to myocardial damage. The ability of salvifolin in vitro and in vivo conditions to correct the functional disturbances of mPTP caused by ED allows recommending it as a potential drug means for the preven-tion and treatment of diabetic cardiomyopathy, caused by mitochondrial dysfunction.

Keywords: 
alloxan-induced diabetes
mitochondria
mPTP
salvifolin

It appears your Web browser is not configured to display PDF files. Download adobe Acrobat или click here to download the PDF file.

References: 
  1. Afanas'ev S.A., Kondrat'eva D.S., Egorova M.V. i dr. Sravnitel'noe issledovanie izmenenij energeticheskogo metabolizma v kardiomiotsitah krys pri postinfarkt nom kardioskleroze i saharnom diabete // Bjulleten' eksperimental'noj biologii i meditsiny. 2013. T. 156. № 8. S. 149–52.
  2. Volchegorskij I.A., Rassohina L.M., Miroshnichenko I.Ju. Dinamika sostojanija sistemy perekisnoe okislenie lipidov – antioksidantnaja zaschita pri alloksanovom diabete u krys // Bjulleten' eksperimental'noj biologii imeditsiny. 2013. T. 155. № 1. S. 31–5.
  3. Egorova M.V., Afanas'ev S.A. Vydelenie mitohondrij iz kletok i tkanej zhivotnyh i cheloveka: sovremennye metodicheskie priemy // Sibirskij meditsinskij zhur nal. 2011. T. 26. № 1. S. 22–8.
  4. Obrezan A.G., Bitsadze R.M. Struktura serdechno- sosudistyh zabolevanij u bol'nyh saharnym diabetom
  5. 2-go tipa, diabeticheskaja kardiomiopatija kak osoboe sostojanie miokarda // Vestnik S.-Peterb. un-ta. 2008. T.11. № 2. S. 47–52.
  6. Hushbaktova Z.A., Tashmuhamedova M.A., Syrov V.N. i dr. Vlijanie sal'vifolina na uglevodnyj i lipidnyj obmen v pecheni krys v uslovijah alloksanovogo diabeta // Ukrainskij biohimicheskij zhurnal. 1992. T. 64. № 3. S. 86–91.
  7. Broekemeier K.M., Dempsey M.E., Pfeiffer D.R. Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria // J. Biol. Chem. 1989. № 264. R. 7826–7830.
  8. Crompton M., Ellinger H., Costi A. Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress // Biochem J 1988. V. 255, № 1. R. 357–360.
  9. Duchen M.R. Roles of mitochondria in health and disease // Diabetes. 2004. V. 53. № 1. R. 96–102.
  10. Eshbakova K.A. Chemical constituents of Pulicaria gnaphalodes Boiss // Med. plants. 2011. V. 3. № 2. R. 161–163.
  11. Halestrap A.P., Clarke S.J., Javadov S.A. Mitochondrial permeability transition pore opening during myocardial
  12. reperfusion − a target for cardioprotection // Card. Res. 2004. V. 61. № 3. R. 372–85.
  13. Halestrap A.P. What is the mitochondrial permeability transition pore? // J. Mol. Cell. Cardiol. 2009. V. 46. № 6. R. 821–831.
  14. He L., Lemasters J.J. Heat shock suppresses the permeability transition in rat liver mitochondria // J. Biol. Chem. 2003. № 278. R. 16755–16760.
  15. Li Y., Johnson N., Capano M., et al. Cyclophilin-D promotes the mitochondrial permeability transition but has opposite effects on apoptosis and necrosis // Biochem. J. 2004. V. 383. № 1. R. 101–109.
  16. Sanchez J.A., Alfonso A., Leirus M., et al. Spongionella secondary metabolites regulate store operated calcium entry modulating mitochondrial functioning in SH-SY5Y neuroblastoma cells // Cell. Physiol. Biochem. 2015. V. 37. № 2. R. 779–792.