Investigation of effects of Lacidipine, Ramipril and Valsartan on DNA damage and oxidative stress occurred in acute and chronic periods following isoproterenol-induced myocardial infarct in rats.
In this study, effects of Lacidipine (LAC), Ramipril (RAM) and Valsartan (VAL) on DNA damage and oxidative stress occurred in acute and chronic periods after isoproterenol (ISO)-induced myocardial infarct (MI) were investigated in rats. LAC, RAM and VAL had been administered by oral gavage at 3, 3 and 30 mg/kg doses, respectively, in acute and chronic periods following MI. In acute MI model, LAC, RAM and VAL had been administered once per day to rat groups during 30 days. On days 29 and 30, the rats of the acute MI control and drug treatment groups were administered 180 mg/kg ISO, subcutaneously at an interval of 24 h. In chronic MI model, LAC, RAM and VAL had been administered to rat groups during 30 days, and on the 1st and 2nd days, the rats of the chronic MI control and drug treatment groups were administered ISO, by the same way. After this period, routine biochemistry indicators of MI, alanin aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase-isoenzymes (CK-MB), troponin I (TnI) and nitric oxide (NO), oxidative stress indicator, has been measured in the serums obtained from rat's blood. Also, 7,8-Dihydro-8-oxo-guanine (8-OHGua), which is an indicator of DNA damage level, has been determined in whole blood. After MI diagnosis, the relationships among the 8-OHGua, NO and clinic MI indicators have been determined. Results have been evaluated by comparing with that of control group. In control groups, the clinic MI indicators have been found to be statistically higher than the drug groups. In parallel to this increase in MI indicators, there have been determined a significant decrease in NO levels and an increase in 8-OHGua level. There was no significant difference in the rat groups which received drugs without MI induction. We have observed that the level of 8-OHGua which increased after MI in both acute and chronic periods decreased by LAC, RAM and VAL when compared to acute and chronic MI control groups. In conclusion, it has been determined that oxidative stress has been increased after ISO induced MI model and this stress reduces NO and even damages DNA. LAC, RAM and VAL may decrease the severity of MI and prevent DNA damage by reducing oxidative stress.
Keles
Mevlut Sait
MS
Department of Biochemistry, Ataturk University, Erzurum, Turkey.
Bayir
Yasin
Y
Suleyman
Halis
H
Halici
Zekai
Z
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D004249:DNA Damage / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use; D006147:Guanine / Q000031:analogs & derivatives / Q000097:blood; D007545:Isoproterenol; D009203:Myocardial Infarction / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D017257:Ramipril / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
C453560:7,8-dihydro-8-oxoguanine; D000959:Antihypertensive Agents; D015415:Biomarkers; D004095:Dihydropyridines; D013777:Tetrazoles; C060285:lacidipine; D009569:Nitric Oxide; D006147:Guanine; D000068756:Valsartan; D014633:Valine; D017257:Ramipril; D007545:Isoproterenol