Effect of I-deprenyl and gliclazide on oxidant stress/antioxidant status and DNA damage in a diabetic rat model


Alper G. , Irer S., Duman E., Caglayan O., Yilmaz C.

ENDOCRINE RESEARCH, cilt.31, ss.199-212, 2005 (SCI İndekslerine Giren Dergi)

  • Cilt numarası: 31 Konu: 3
  • Basım Tarihi: 2005
  • Doi Numarası: 10.1080/07435800500371805
  • Dergi Adı: ENDOCRINE RESEARCH
  • Sayfa Sayısı: ss.199-212

Özet

Background: This study investigates the possible effect of monoamine oxidase inhibitor ( MAOI), selegyline ( 1-deprenyl), in combination with oral antidiabetic-gliclazide ( OAD), in preventing oxidative stress in streptozotocin-induced diabetes model in male Swiss Albino rats by measuring oxidant stress/DNA damage and antioxidant levels. Methods: Diabetic rats were divided into four groups ( n = 10) as ( 1) diabetic untreated ( DM), ( 2) deprenyl treated ( DM + D), ( 3) gliclazide treated ( DM + O), and ( 4) gliclazide and deprenyl treated ( DM + O + D). Controls were divided into two groups ( n = 8) ( 1) untreated ( C), and ( 2) deprenyl treated ( C + D). Gliclazide 5 mg/kg and/or MAOI 0.25 mg/kg daily were given orally by gavage for 4 weeks. At the end of the 12th week, catalase and superoxide dismutase ( SOD) levels in erythrocyte lysates ( EL); total antioxidant status ( TAS), 8-hydroxy-deoxyguanosine ( 8-OHdG), malondialdehyde ( MDA), and vitamin A and E levels in plasma, MDA, and MAO in liver homogenates were determined. Results: Diabetic rats showed a decrease in EL-SOD, plasma TAS, and vitamin E, and an increase in plasma 8-OHdG, plasma, and liver MDA levels ( p < 0.05). Gliclazide and/or deprenyl decreased 8OHdG levels and increased antioxidant levels and survival when compared with untreated diabetic rats ( p < 0.05). The lowest 8-OHdG levels were determined in the DM + O + D group. Conclusions: The combined treatment of deprenyl and gliclazide may contribute to the control of the physiopathological mechanisms underlying both the process of aging and type 2 diabetes by reducing oxidant stress and DNA damage, improving antioxidant status, and increasing survival, and may have implications for further clinical studies.