Neuroprotective Effect of Cilostazol against Focal Cerebral Ischemia via Antiapoptotic Action in Rats

Choi, Jae Moon; Shin, Hwa Kyoung; Kim, Ki Young; Lee, Jeong Hyun; Hong, Ki Whan

doi:10.1124/jpet.300.3.787

Cited by 135 publications

(109 citation statements)

References 34 publications

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“…Previous studies (20,21) have shown that cilostazol reverses decreases in Bcl-2 protein and increases in Bax protein production and cytochrome c release. The maxi-K channel opening-coupled upregulation and down-regulation of PTEN phosphorylation with resultant increases in Akt and CREB phosphorylation and increased Bcl-2 protein levels have also been demonstrated (12).…”

Section: Discussionmentioning

confidence: 91%

“…Previous studies have shown that Bid was processed by caspases in NOinduced apoptosis (21,52). However, the molecular role of Bid in NO-induced apoptosis has not been fully delineated.…”

Section: Discussionmentioning

confidence: 98%

“…The recent observation that cilostazol inhibits apoptosis under several circumstances (12,(20)(21)(22) raises the interesting possibility that it can be considered as a therapy for diseases associated with excess apoptosis. Although apoptotic chondrocyte death is not always a widespread phenomenon in cartilage aging or OA cartilage degeneration (38), obviously any kind of cell death is detrimental to the tissue.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it seems to reduce inflammation and inhibit MMP expression by increasing AMP and inhibiting the p38/ JNK pathway (19). Previous studies have demonstrated that cilostazol inhibits apoptosis under several circumstances (12,(20)(21)(22). In those studies, cilostazol was shown to prevent lipoprotein particle-induced apoptosis in human umbilical vein endothelial cells (HUVECs) (22), lipopolysaccharide-induced apoptosis in HUVECs (20), and ischemic injury-induced apoptosis in neural cells (12,21).…”

Section: Conclusion Our Findings Indicate That Cilostazol Prevents Nmentioning

confidence: 99%

“…Previous studies have demonstrated that cilostazol inhibits apoptosis under several circumstances (12,(20)(21)(22). In those studies, cilostazol was shown to prevent lipoprotein particle-induced apoptosis in human umbilical vein endothelial cells (HUVECs) (22), lipopolysaccharide-induced apoptosis in HUVECs (20), and ischemic injury-induced apoptosis in neural cells (12,21). Notably, protein kinase CK2 (PKCK2) was reported to be involved in the prevention of apoptosis by cilostazol (12,23).…”

Section: Conclusion Our Findings Indicate That Cilostazol Prevents Nmentioning

confidence: 99%

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Cilostazol protects rat chondrocytes against nitric oxide–induced apoptosis in vitro and prevents cartilage destruction in a rat model of osteoarthritis

Lee

Song

Shin

et al. 2008

Arthritis & Rheumatism

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Objective. To examine whether cilostazol, a selective phosphodiesterase type III inhibitor, protects rat articular chondrocytes against nitric oxide (NO)-induced apoptosis and prevents cartilage destruction in mono-iodoacetate-induced osteoarthritis (OA) in a rat model in which inducible nitric oxide synthase (iNOS) is expressed.Methods. The NO donor sodium nitroprusside was administered to rat articular chondrocytes that had been pretreated with cilostazol. Induction of apoptosis was evaluated by DNA electrophoresis and pulsed-field gel electrophoresis. The expression level and the subcellular location of apoptosis-associated factors were examined by Western blot analysis and confocal microscopy, respectively. Protein kinase CK2 (PKCK2) activity was also assayed. To examine whether orally administered cilostazol prevents cartilage destruction in vivo, cartilage samples obtained from rats with experimentally induced OA were subjected to hematoxylin and eosin, Safranin O, and TUNEL staining and immunohistochemical analysis of iNOS expression.Results. Cilostazol prevented NO-induced reduction in viability, in a dose-dependent manner. It also prevented the up-regulation of phosphorylated p53 and p38, the down-regulation of heme oxygenase 1, the subcellular translocation of apoptosis-inducing factor and cytochrome c, and the activation of caspases 3, 7, and 8 induced by NO treatment, indicating that cilostazol prevented NO-induced cell death by blocking apoptosis. In addition, cilostazol prevented NO-induced translocation of cleaved Bid onto mitochondria, and caused phosphorylated Bid to accumulate in the nucleus and cytosol. Cilostazol prevented the down-regulation of PKCK2 and the reduction in PKCK2 activity induced by NO, indicating that its apoptosis-preventing activity was mediated via PKCK2. It also prevented chondrocyte apoptosis and cartilage destruction in a rat model of experimentally induced OA. Conclusion. Our findings indicate that cilostazol prevents NO-induced apoptosis of chondrocytes via PKCK2 in vitro and prevents cartilage destruction in a rat model of OA.

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Section: Discussionmentioning

confidence: 91%

“…Previous studies have shown that Bid was processed by caspases in NOinduced apoptosis (21,52). However, the molecular role of Bid in NO-induced apoptosis has not been fully delineated.…”

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Conclusion Our Findings Indicate That Cilostazol Prevents Nmentioning

confidence: 99%

Section: Conclusion Our Findings Indicate That Cilostazol Prevents Nmentioning

confidence: 99%

See 3 more Smart Citations

Cilostazol protects rat chondrocytes against nitric oxide–induced apoptosis in vitro and prevents cartilage destruction in a rat model of osteoarthritis

Lee

Song

Shin

et al. 2008

Arthritis & Rheumatism

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Pharmacological Activation of Mitochondrial Biogenesis for the Treatment of Various Pathologies

Gibbs

Scholpa

Beeson

et al. 2018

Mitochondrial Dysfunction Caused by Drugs and Environmental Toxicants

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Cilostazol against 2,4,6‐trinitrobenzene sulfonic acid‐induced colitis: Effect on tight junction, inflammation, and apoptosis

Al‐Kishali

Fattah

Mohammad³

et al. 2019

JGH Open

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Background Inflammatory bowel diseases are immunologically mediated disorders of gastrointestinal tract, characterized by dysregulated immune responses that result in a chronic intestinal inflammation. The antiplatelet cilostazol (CS), a phosphodiesterase‐III inhibitor, exerted a beneficial effect on several models of gastrointestinal diseases; however, the full mechanism of action in this context has not been unveiled. Aim The current study aimed to elucidate the potential role of CS in a 2,4,6‐trinitrobenzene sulfonic acid (TNBS)‐induced colitis model. Methods Male Wistar rats were divided into a sham group and groups treated with sulfasalazine (500 mg/kg), CS (50 and 100 mg/kg), and a combination (sulfasalazine/CS 50 mg/kg). All treatments were administered orally 15 days, with TNBS rectal administration on the 11th day. Results TNBS‐produced colitis manifested as a decrease in the epithelial junctional adhesion molecule‐A (JAM‐A) and as an increase in trefoil factor‐3, ulcerative area, and colon mass index, parameters that collaborate with the gross macroscopic changes in colon tissue. In addition, TNBS increased hemeoxygenase‐1, nuclear factor‐kappa B, P‐selectin, and myeloperoxidase, as well as the apoptotic ratio of Bax/Bcl‐2. Administration of CS alone, especially at the high dose level, attenuated the severity of TNBS‐induced colitis in a sulfasalazine‐comparable manner. In addition, a better effect was mediated by the combination regimen, which succeeded in normalizing most of the measured parameters. Conclusion CS protected the colon against TNBS through its anti‐inflammatory and antiapoptotic effects along with maintaining cellular tight junctions (TJs). Furthermore, CS can be beneficial as an add‐on drug with the conventional treatments of colitis.

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Neuroprotective Effect of Cilostazol against Focal Cerebral Ischemia via Antiapoptotic Action in Rats

Cited by 135 publications

References 34 publications

Cilostazol protects rat chondrocytes against nitric oxide–induced apoptosis in vitro and prevents cartilage destruction in a rat model of osteoarthritis

Cilostazol protects rat chondrocytes against nitric oxide–induced apoptosis in vitro and prevents cartilage destruction in a rat model of osteoarthritis

Pharmacological Activation of Mitochondrial Biogenesis for the Treatment of Various Pathologies

Cilostazol against 2,4,6‐trinitrobenzene sulfonic acid‐induced colitis: Effect on tight junction, inflammation, and apoptosis

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