Effect of SIRT2 Inhibition on Developing Fibrosis in D-Galactose-Induced Aging Model

Bahar A. N., Keskin Aktan A., Sonugür F. G., Akarca Dı̇zakar. S. Ö., Akbulut K. G.

47th Turkish Physiology Congress, Antalya, Türkiye, 1 - 04 Kasım 2022, cilt.237, sa.727, ss.22

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 237
  • Doi Numarası: 10.1111/apha.13909
  • Basıldığı Şehir: Antalya
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.22
  • Marmara Üniversitesi Adresli: Evet

Özet

AIM:  Aging  is  a  risk  factor  for  fibrosis  and  liver  injury.  SIRT2 inhibition  has  been  shown  to  have  a  protective  effect  on  the mechanism of renal interstitial fibrosis. In our study, it was aimed to  determine  the  effect  of  SIRT2  inhibition  by  AGK-2  on  liver functions  and  its  role  in  the  fibrosis  process  in  the  aging  model caused by D-galactose (D-GAL).

METHODS:  A  total  of  32  3-month-old  Sprague  Dawley  rats  were used  in  the  study.  Rats  were  divided  into  4  groups  as  Control,  D-GAL, Solvent+D-GAL, D-GAL+AGK2+Solvent. D-galactose (150 mg/ kg/day),    AGK-2  (10μM/bw)  as  a  specific  SIRT2  inhibitor, 4%DMSO+PBS  as  a  solvent  were  applied  to  the  experimental groups  and  physiological  saline  was  applied  to  the  control  group for  10  weeks.  Biochemical  parameters  (ALT,  AST,  platelet  count, LDH,  HDL,  VLDL,  total  cholesterol,  triglyceride)  were  measured  in plasma.AST-ALT  Ratio,  AST-Platelet  Ratio  Index  (APRI),  liver  index  (liver weight/body  weight)  were  calculated.  SIRT2  levels  in  liver  tissues were determined by western blot (WB) and immunohistochemical (IHC)  analysis.The expression level of TGF β, β catenin, PDGFBB genes  was  determined  by  real-time-polymerase  chain  reaction. Histopathological scoring was performed to detect tissue damage.For  statistical  analysis,  the  data  obtained  from  the  study  were presented as “mean±standard deviation”.One-way ANOVA (post-hoc  LSD)  test  was  used  to  determine  the  intergroup  differences, and   Pearson   correlation   test   was   used   to   determine   the relationshipsbetween the variables(p<0.05).

RESULTS: D-Galactose administration increased AST, AST-ALT ratio, APRI, SIRT2 protein expression, TGF β, β catenin mRNA levels in liver  tissue.  AGK-2  application  decreased  all  theseparameters. SIRT2 expression (WB) is positively correlated with AST,APRI index, TGF  β1,  β-catenin  mRNA  expression.  SIRT2(IHC)  is  positively correlated with AST/ALT and APRI index.

CONCLUSION:  It  is  thought  that  SIRT2  inhibition  may  be  effective in   improving   aging-related   fibrotic   changes   in   the   liver   and preventing aging-related loss of function.

Keywords:D-Galactose, Fibrosis, SIRT2 inhibition, TGFβ, β catenin,Liver.