Effect of l-Deprenyl and Gliclazide on Oxidant Stress/Antioxidant Status and DNA Damage in a Diabeticrat Model

Abstract

Background: This study investigates the possible effect of monoamine oxidase inhibitor (MAOI), selegyline (l-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 [] diabetic untreated (DM), [] deprenyl treated (DM + D), [] gliclazide treated (DM + O), and [] gliclazide and deprenyl treated (DM + O + D). Controls were divided into two groups (n = 8) [] untreated (C), and [] 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.

Keywords:

• Diabetes mellitus
• 8-OHdG
• l-Deprenyl
• Gliclazide
• Oxidant stress
• Antioxidant status

ACKNOWLEDGMENT

This work was kindly supported by the Research Fund of Ege University (2002 TIP 022). We are thankful to Gulgun Kececioglu and Asil Gonul from Central Research Laboratory of Ege University School of Medicine for their kind technical support for the HPLC analysis of the study.