Protective effects of cilostazol and levosimendan on lung injury induced by lower limb ischemia-reperfusion

Önem, Gökhan; Saçar, Mustafa; Aybek, Hülya; Kocamaz, Erdogan; Adalı, Fahri; Saçkan, Kadir Gökhan; Baltalarlı, Ahmet

doi:10.5606/tgkdc.dergisi.2012.110

Cited by 11 publications

(14 citation statements)

References 22 publications

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“…These findings are in agreement with earlier studies on lung injury induced by lower limb I/R [57] and spinal cord I/R-induced injury [58]. These reports support the possible antioxidant capacity of cilostazol, which could be one of its renoprotective mechanistic pathways.…”

Section: Discussionsupporting

confidence: 93%

Cilostazol Renoprotective Effect: Modulation of PPAR-γ, NGAL, KIM-1 and IL-18 Underlies Its Novel Effect in a Model of Ischemia-Reperfusion

2014

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Cilostazol, a phosphodiesterase-III inhibitor, reportedly exhibits positive effects against ischemia/reperfusion (I/R)-induced injury in several models. However, its potential role against the renal I/R insult has not been elucidated. To test whether the PPAR-γ (of peroxisome proliferator activated receptor gamma) pathway is involved in the cilostazol effect, rats were randomized into sham, I/R, cilostazol (50 and 100 mg/kg per day, orally), pioglitazone (3 and 10 mg/kg per day, orally) and their combination at the low dose levels. Drugs regimens were administered for 14 days prior to the I/R induction. Pretreatment with cilostazol or pioglitazone provided significant protection against the I/R-induced renal injury as manifested by the attenuated serum levels of creatinine, blood urea nitrogen and cystatin C. Both drugs have also opposed the I/R-induced elevation in tissue contents/activity of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (Κim-1), nuclear factor-κB, interleuκin-18, caspase-1, as well as malondialdehyde, iNOS, myeloperoxidase, ICAM-1 and VCAM-1. Nevertheless, the drugs increased both the PPAR-γ transcriptional activity and the content of glutathione. Furthermore, combining the two low doses of both drugs produced effects comparable to that of the high dose level of either drug, advocating the fortification of pioglitazone renoprotective effect when given concomitantly with cilostazol. In conclusion, cilostazol purveyed conceivable novel renoprotective mechanisms and alleviated incidents associated with acute renal injury either alone or in combination with pioglitazone partially via the elevation of PPAR-γ besides the amendment of the aforementioned biomarkers.

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Section: Discussionsupporting

confidence: 93%

Cilostazol Renoprotective Effect: Modulation of PPAR-γ, NGAL, KIM-1 and IL-18 Underlies Its Novel Effect in a Model of Ischemia-Reperfusion

2014

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“…Lipid peroxidation seen in diabetic patients further increases the damage to distant organs following reperfusion of the myocardium exposed to ischaemia ( 4 ). Among the distant organs, indirect damage seen after I/R is defined best in the lung ( 5 ) and is associated with these mechanisms. Therefore, acute lung injury may indirectly develop during and after pulmonary oedema.…”

mentioning

confidence: 99%

Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

Kip

Çelik

Bilge

et al. 2015

Libyan Journal of Medicine

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ObjectiveDiabetic complications and lipid peroxidation are known to have a close association. Lipid peroxidation commonly occurs at sites exposed to ischaemia, but distant organs and tissues also get damaged during ischaemia/reperfusion (I/R). Some of these targets are vital organs, such as the lung, liver, and kidney; the lung is the most frequently affected. The aim of our study was to investigate the effects of dexmedetomidine on I/R damage in lung tissue and on the oxidant/anti-oxidant system in diabetic rats.Material and methodsDiabetes was induced with streptozotocin (55 mg/kg) in 18 Wistar Albino rats, which were then randomly divided into three groups (diabetes control (DC), diabetes plus ischaemia-reperfusion (DIR), and diabetes plus dexmedetomidine-ischaemia/reperfusion (DIRD)) after the effects of diabetes were clearly evident. The rats underwent a left thoracotomy and then ischaemia was produced in the myocardium muscle by a left anterior descending artery ligation for 30 min in the DIR and DIRD groups. I/R was performed for 120 min. The DIRD group received a single intraperitoneal dose of dexmedetomidine (100 µg/kg); the DIR group received no dexmedetomidine. Group DC was evaluated as the diabetic control group and also included six rats (C group) in which diabetes was not induced. These mice underwent only left thoracotomy and were closed without undergoing myocardial ischaemia. Histopathological changes, activities of catalase (CAT) and glutathione-S-transferase anti-oxidant enzymes, and malondialdehyde (MDA) levels were evaluated in the lung tissues of all rats.ResultsNeutrophil infiltration/aggregation was higher in the DIR group than in the C, DC, and DIRD groups (p=0.001, p=0.013, and p=0.042, respectively). The lung injury score was significantly higher in the DIR group than in the C and DC groups (p<0.0001 and p=0.024, respectively). The levels of MDA were significantly higher in the DIR group than in the C and DIRD groups. CAT activity was significantly higher in the DIR group than in the DIRD and C groups.ConclusionOur results confirm that dexmedetomidine has protective effects against the lung damage resulting from I/R in diabetic rats. Future studies conducted to evaluate the effects of the use of dexmedetomidine on damage to various organs following different I/R durations may help understanding possible protective effects of dexmedetomidine and underlying mechanisms in tissue damage related to I/R injury.

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“…They showed cilostazol and diltiazem were effective to decrease renal I/R injury. In another experimental study investigating the protective effects of cilostazol and levosimendan on lung injury after lower extremity ischemia, Onem et al [16] performed 60 min abdominal aortic crossclamping and evaluated malondialdehyde levels, superoxide dismutase activity, and glutathione levels in the lung tissues. The authors showed that cilostazol and levosimendan restored malondialdehyde levels, superoxide dismutase activity, glutathione levels, and lung injury scores.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of cilostazol and rosuvastatin on acute kidney injury-induced lung injury using TNF-a and HIF-1a immunoreactivities

İşcan¹

2018

Damar Cer Derg

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Bu çalışmada deneysel bir modelde ameliyat öncesi silostazol ve rosuvastatinin izole böbrek iskemi-reperfüzyon (I/R) hasarı sonrasında oluşan akciğer reperfüzyon hasarı üzerine etkileri araştırıldı. Gereç ve Yöntemler: Toplam 35 adet dişi Sprague-Dawley sıçan rastgele beş gruba ayrıldı (n=7). Medyan laparotomi ve her iki böbreğe 45 dk. iskemi uygulandı. Cerrahi girişimden üç gün öncesinden başlayarak (20 mg/kg silostazol, 10 mg/kg rosuvastatin ve 20 mg/kg silostazol+10 mg/kg rosuvastation) oral tedaviler uygulandı. Cerrahiden bir gün sonra akciğer dokusu örnekleri alındı. Akciğer çapraz kesit dokularının immünhistokimyasal incelemesi için tümör nekroz faktör-a (TNF-a) ve hipoksi ile indüklenmiş faktör-1a (HIF-1a) antikorları kullanıldı. Bulgular: TNF-a immünreaktivitesi I/R+silostazol, I/R+rosuvastatin ve I/R+silostazol+rosuvastatin gruplarında, I/R grubuna kıyasla anlamlı düzeyde azalmış tespit edildi (p<0.05). Akciğer TNF-a immünreaktivitesi I/R+rosuvastatin ve I/R+cilostazol+rosuvastatin gruplarında, kontrol grubuna kıyasla anlamlı düzeyde artmış olarak bulundu (p<0.05). HIF-1a immünreaktivitesi I/R+cilostazol, I/R+rosuvastatin ve I/R+cilostazol+rosuvastatin gruplarında, I/R grubuna kıyasla anlamlı düzeyde azalmış tespit edildi (p<0.05). HIF-1a immünreaktivitesi I/R+cilostazol, I/R+rosuvastatin ve I/R+cilostazol+rosuvastatin gruplarında, kontrol grubuyla kıyaslandığında benzer bulundu (p>0.05). Sonuç: Silostazol ve rosuvastinin böbrek I/R ile oluşan uzak akciğer reperfüzyon hasarı üzerinde profilaktik etkileri mevcuttur. Bu ilaçların periferik arter hastalıklarında tek başına veya birlikte kullanımı perioperatif dönemde faydalı olabilir.

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Protective effects of cilostazol and levosimendan on lung injury induced by lower limb ischemia-reperfusion

Cited by 11 publications

References 22 publications

Cilostazol Renoprotective Effect: Modulation of PPAR-γ, NGAL, KIM-1 and IL-18 Underlies Its Novel Effect in a Model of Ischemia-Reperfusion

Cilostazol Renoprotective Effect: Modulation of PPAR-γ, NGAL, KIM-1 and IL-18 Underlies Its Novel Effect in a Model of Ischemia-Reperfusion

Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

Protective effect of cilostazol and rosuvastatin on acute kidney injury-induced lung injury using TNF-a and HIF-1a immunoreactivities

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