Filiz KAÇMAZ, Oguzhan OZCAN, Abdullah ARPACI, Ercan AYAZ, Hamdullah Suphi BAYRAKTAR, Sadık GÖRÜR

Deneysel böbrek iskemi-reperfüzyon modelinde lipoik asit ve dihidrolipoat kullanımının etkilerinin incelenmesi

Amaç: İskemi/reperfüzyon (I/R) doku hasarına neden olarak akut böbrek hasarına yol açar. Bu çalışmada, deneysel böbrek iskemi-reperfüzyon modelinde uzun ve kısa süreli ALA ve kısa süreli DHLA kullanımının oksidatif stres belirteçleri üzerine etkilerinin araştırması amaçlanmıştır. . Yöntem: Kırk adet erkek rat (250-300 gr) 5 gruba ayrılmıştır: kontrol grubu; I/R grubu; uzun vadeli ALA+IR grubu; kısa vadeli ALA+IR grubu ve kısa vadeli DHLA+IR grubu. 45 dakika süreyle iskemi, ardından 4 saat süreyle reperfüzyon uygulanmıştır. Doku örneklerinde Tiyobarbitürik asid reaktif maddeler (TBARM), katalaz (CAT), süperoksit dismutaz (SOD) ve glutatyon peroksidaz (GSH-Px) aktiviteleri ile total antioksidan durum (TAS) ve total oksidatif stres kapasitesi (TOS) spektrofotometrik olarak ölçülmüştür. Doku örnekleri ayrıca histopatolojik olarak analiz edilmiştir. Bulgular: Uzun ve kısa süreli ALA uygulanan grupta ve kısa süreli DHLA uygulanan grupta I/R grubuna kıyasla TBARM (Kontrol: 0.38±0.05, I/R: 1.37±0.17, uzun vadeli ALA+IR grubu: 1.025±0.15, kısa vadeli ALA+IR grubu: 0.68±0.09, kısa vadeli DHLA+IR grubu: 0,38±0,04 (nmol/mg protein); p<0.001), CAT (Kontrol: 0.12±0.02, I/R: 0.04±0.008, uzun vadeli ALA+IR grubu: 0,07±0,01, kısa vadeli ALA+IR grubu: 0,06±0,008, kısa vadeli DHLA+IR grubu: 0.08±0.01 (k/mg protein; p<0.001), GSH-Px (Kontrol: 0.45±0.04, I/R: 0.21±0.028, uzun vadeli ALA+IR grubu: 0.37±0.05, kısa vadeli ALA+IR grubu: 0.34±0.05, kısa vadeli DHLA+IR grubu: 0.37±0.04 (U/mg protein); p<0.001), ve serum OSI (Kontrol: 1.32±0.15, I/R: 3.08±0.44, uzun vadeli ALA+IR grubu: 1.775±0.21, kısa vadeli ALA+IR grubu: 1.85±0.37, kısa vadeli DHLA+IR grubu: 1.53±0.21 (arbitary unit); p<0.001) seviyelerinde iyileşme gözlemlenmiştir. Bu bulgular, histopatolojik doku örneklerinde DHLA uygulanan grupta daha belirgindir Sonuç: Hem uzun süreli hem de kısa süreli ALA uygulamalarının renal I/R hasarının tedavisi için potansiyele sahip olduğu düşünülmektedir. Ayrıca DHLA’nın, ALA’dan daha etkili olduğu düşünülmektedir.

Anahtar Kelimeler:

İskemik Hasar, Reperfüzyon, Lipoik Asit, Dihidrolipoat, Antioksidan Enzim

Investigation of the effects of lipoic acid and dihydrolipoate on experimental renal ischemia-reperfusion model

Objective: Ischemic/reperfusion (I/R) causes tissue injury and the leading cause of acute kidney injury. In this study, we aimed to investigate the effects of the long and short-term usage of ALA and short-term DHLA on oxidative stress markers in the experimental renal ischemia-reperfusion model. Methods: Forty male rats (250 to 300 gr) were divided into 5 groups: control; I/R group; long-term ALA+IR group; short-term ALA+IR group; and short-term DHLA+IR group. Ischemia was carried out for 45 minutes followed by reperfusion for 4 hours. Thiobarbituric acid reactive sunstances (TBARM), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities in tissue samples and serum total antioxidant status (TAS) and total oxidative stress (TOS) assayed by the spectrophotometrically. Tissue samples were investigated by histopathological analyzes. Results: TBARM (Control: 0.38±0.05. I/R: 1.37±0.17, long-term ALA-treated group:1.025±0.15, short-term ALA-treated group: 0.68±0.09, short-term DHLA-treated group: 0.38±0.04 (nmol/mg protein); p<0,001) CAT (Control: 0.12±0.02, I/R: 0.04±0.008, long-term ALA-treated group: 0.07±0.01, short-term ALA-treated group:0.06±0.008, short-term DHLA-treated group: 0.08±0.01 (k/mg protein); p<0.001), GSH-Px (Control: 0.45±0.04, I/R: 0.21±0.028, long-term ALA-treated group: 0.37±0.05, short-term ALA-treated group :0.34±0.05, short-term DHLA-treated group: 0.37±0.04 (U/mg protein); p<0.001), and serum OSI levels (Control: 1.32±0.15, I/R: 3.08±0.44, long-term ALA-treated group: 1.775±0.21, short-term ALA-treated group: 1.85±0.37, short-term DHLA-treated group: 1.53±0.21 (arbitrary unit) ; p<0.001) were improved in the long and short-term ALA-treated group and short-term DHLA-treated group compared to the I/R group. These findings were more prominent in histopathological tissue samples in the DHLA-treated group. Conclusion: We consider that both long-term and short-term ALA applications have the potential for the treatment of renal I/R damage. Besides, DHLA is more effective than ALA.

Keywords:

Ischemic Damage, Reperfusion, Lipoic Acid, Dihydrolipoat, Antioxidant Enzyme,

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