Effects of cilostazol on oxidative stress, systemic cytokine release, and spinal cord injury in a rat model of transient aortic occlusion.
BACKGROUND
Cilostazol is a phosphodiesterase inhibitor that has anti-inflammatory potential in addition to vasodilator and antiplatelet effects. The aim of this study was to determine the influence of cilostazol on biochemical markers of oxidative damage, proinflammatory cytokine release, and spinal cord injury after transient aortic occlusion in rats.


METHODS
Animals were randomized into 3 groups. Sham group rats were subjected to laparotomy without aortic occlusion. Control group rats were pretreated with intraperitoneal dimethyl sulfoxide, and cilostazol group rats received intraperitoneal cilostazol (20 mg/kg/day) for 3 days before the induction of ischemia. Ischemia was induced by clamping of the infrarenal aorta, and 48 hours after reperfusion, Tarlov grades were assessed and spinal cord conduction velocities (SCCVs) were measured using epidural electrical stimulation. Erythrocyte superoxide dismutase (SOD) and catalase activities and plasma malondialdehyde, serum tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels were analyzed. Spinal cord histopathology was examined to determine neuronal damage and tissue inflammation.


RESULTS
Aortic occlusion caused significant increases in SOD, catalase activities, and malondialdehyde and cytokine levels accompanied by spinal cord injury. Cilostazol significantly reduced malondialdehyde levels but did not significantly alter the activations of antioxidant enzymes, levels of proinflammatory cytokines, or histologic severity of inflammation. The differences regarding the results of Tarlov grading, SCCVs, and neuronal viability between the ischemic and cilostazol pretreated groups were statistically nonsignificant.


CONCLUSIONS
The present experimental study indicated that cilostazol pretreatment used in this study before aortic occlusion decreased lipid peroxidation, which may be related to the reduction of reactive oxygen species. Cilostazol did not significantly suppress systemic cytokine release and prevent spinal cord inflammation and injury; however, it did show some benefit. Additional investigations might be needed to determine the critical dose of cilostazol for clarifying the protective role of this drug in spinal cord ischemia/reperfusion injury.
Department of Cardiovascular Surgery, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey. Electronic address: drtunaykurtoglu@yahoo.com.
Tunay
T
Kurtoglu
Department of Biophysics, Institute of Health Sciences, Adnan Menderes University, Aydin, Turkey.
Harun
H
Basoglu
Department of Cardiovascular Surgery, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
Erdem Ali
EA
Ozkisacik
Department of Pathology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
Nesibe Kahraman
NK
Cetin
Department of Pathology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
Canten
C
Tataroglu
Department of Biochemistry, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
Cigdem
C
Yenisey
Department of Cardiovascular Surgery, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
Berent
B
Discigil
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001012:Aorta, Abdominal / Q000503:physiopathology / Q000601:surgery*; D015415:Biomarkers / Q000097:blood; D002470:Cell Survival / Q000187:drug effects; D000077407:Cilostazol; D003250:Constriction; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000097:blood*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013116:Spinal Cord / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D013777:Tetrazoles; D000077407:Cilostazol