Cerebellum and Oxidative Stress in Natural and Accelerated Aging Model

Kavak H., Bahar A. N., Keskin Aktan A., Akbulut K. G.

47th Turkish Physiology Congress, Antalya, Türkiye, 1 - 04 Kasım 2022, cilt.237, sa.727, ss.61

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 237
  • Doi Numarası: 10.1111/apha.13910
  • Basıldığı Şehir: Antalya
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.61
  • Marmara Üniversitesi Adresli: Evet

Özet

AIM:  Intracerebroventricular  administration  of  galactose  causes motor  coordination  deficiency  by  decreasing  glutathione  (GSH) level  in  the  cerebellum.  It  has  been  shown  that  aging  increases oxidative  stress  and  Sirtuin  2  (Sirt2)  expression  in  rat  cerebellum tissue  and  Sirt2  inhibition  has  a  protective  effect  in  aging.  In  our study, we aimed to investigate the effect of AGK-2 administration, a specific Sirt2 inhibitor, on oxidative stress in an accelerated aging model with natural and D-galactose (D-GAL) administration.

METHODS: In the study, 7 groups were formed using 48 male rats of  Wistar  (W)  and  Sprague-Dawley  (SD)  species;1)  Young-Control (3  months,  n=6),  2)  Young-AGK-2  (3  months,  n=6),  3)  Old-Control (22  months,  n=6),  4)  Old-AGK-2  (22  months,  n=6),  5)  D-GAL  (3 months,  n=9),  6)  Solvent+D-GAL  (3  months,  n=8),  7)  Solvent+D-GAL+AGK-2  (3  months,  n=7).  Control  groups  were  given  4% DMSO+PBS,   and   experimental   groups   were   given   AGK-2   (10 μM/bw) subcutaneously (SC). For the accelerated aging model, D-galactose  (150  mg/kg/day,  SC)  was  administered  for  10  weeks. Malondialdehyde (MDA) and GSH levels in cerebellum tissue were measured   by   spectrophotometric   method.In   the   statistical analysis,  one-way  ANOVA  (post-hoc  LSD)  was  used  to  determine the  differences  between  groups.  The  statistical  significance  level was set at p<0.05.

RESULTS: The D-GAL administration increased the cerebellum MDA level significantly compared to the young control group (p<0.001). In  the  D-GAL  group,  AGK-2  administration  decreased  the  MDA levels  and  increased  the  GSH  levels  (p=0.003;  p=0.006).  D-GAL administration  increased  MDA  levels  more  and  decreased  GSH levels significantly compared to aged rats (p=0.006; p<0.001). AGK-2 administration in natural aging was found to be more effective in increasing  GSH  levels  compared  to  the  accelerated  aging  model (p<0.001).

CONCLUSION:  Both  models  compared  increased  oxidant  stress  in the cerebellum. AGK-2 application was found to be more effective than D-GAL on oxidant stress in natural aging.

Keywords:AGK-2,  Accelerated  aging,  Cerebellum,  D-galactose, Natural aging, Oxidative Stress