Anti‐inflammatory activity of creatine supplementation in endothelial cells <i>in vitro</i>

Nomura, Akihiro; Zhang, Minjie; Sakamoto, Tohru; Ishii, Yukio; Morishima, Yuko; Mochizuki, M.; Kimura, Tōru; Uchida, Yoshiyuki; Sekizawa, Kiyohisa

doi:10.1038/sj.bjp.0705316

Cited by 64 publications

(77 citation statements)

References 33 publications

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“…In the present study, we also show that the antidepressant-like effect of creatine and ketamine are dependent on adenosine A 2A receptor modulation, since the pretreatment of mice with caffeine or ZM241385, an adenosine A 2A receptor antagonist, prevented the antidepressant-like effect of these compounds in the TST. In addition, literature data show that creatine produced anti-inflammatory effects in endothelial cells that were suppressed by ZM241385 [63]. Similar to our results, the anti-inflammatory effect of ketamine was also blocked by ZM241385 treatment [64].…”

Section: Discussionsupporting

confidence: 91%

Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A1 and A2A receptor activation

Cunha

Pazini

Rosa

et al. 2015

Purinergic Signalling

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The benefits of creatine supplementation have been reported in a broad range of central nervous systems diseases, including depression. A previous study from our group demonstrated that creatine produces an antidepressant-like effect in the tail suspension test (TST), a predictive model of antidepressant activity. Since depression is associated with a dysfunction of the adenosinergic system, we investigated the involvement of adenosine A 1 and A 2A receptors in the antidepressant-like effect of creatine in the TST. The anti-immobility effect of creatine (1 mg/kg, po) or ketamine (a fast-acting antidepressant, 1 mg/kg, ip) in the TST was prevented by pretreatment of mice with caffeine (3 mg/kg, ip, nonselective adenosine receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (2 mg/kg, ip, selective adenosine A 1 receptor antagonist), and 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-ylamino]ethyl)-phenol (ZM241385) (1 mg/kg, ip, selective adenosine A 2A receptor antagonist). In addition, the combined administration of subeffective doses of creatine and adenosine (0.1 mg/kg, ip, nonselective adenosine receptor agonist) or inosine (0.1 mg/kg, ip, nucleoside formed by the breakdown of adenosine) reduced immobility time in the TST. Moreover, the administration of subeffective doses of creatine or ketamine combined with N-6-cyclohexyladenosine (CHA) (0.05 mg/kg, ip, selective adenosine A 1 receptor agonist), N-6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)ethyl]adenosine (DPMA) (0.1 mg/kg, ip, selective adenosine A 2A receptor agonist), or dipyridamole (0.1 μg/mouse, icv, adenosine transporter inhibitor) produced a synergistic antidepressant-like effect in the TST. These results indicate that creatine, similarly to ketamine, exhibits antidepressant-like effect in the TST probably mediated by the activation of both adenosine A 1 and A 2A receptors, further reinforcing the potential of targeting the purinergic system to the management of mood disorders.

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Section: Discussionsupporting

confidence: 91%

Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A1 and A2A receptor activation

Cunha

Pazini

Rosa

et al. 2015

Purinergic Signalling

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“…24 Creatine can prevent cell damage with two possible mechanisms: stabilization of cellular membranes and maintenance of ATP. 18 In addition to these Nomura et al 25 reported that creatine has an anti-inflammatory effect on endothelial cells. After ischemic insults, ATP production through oxidative pathways is reduced resulting in cell damage.…”

Section: Discussionmentioning

confidence: 99%

Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity

et al. 2014

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Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69 M Â 10 À5 at 24th hour and 3.93 M Â 10 À6 at 48th hour. IC50 dose for pioglitazone was 1.61 M Â 10 À3 at 24th hour and 2.85 M Â 10 À4 at 48th hour. Although cells were treated the dose of 40,225 mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatininduced nephrotoxicity.

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“…23 In addition, antiinflammatory activities of creatine on endothelial cells have been shown recently. 4 Berneburg et al 5 observed that creatine supplementation normalized ultraviolet-A-irradiation induced mitochondrial mutagenesis and showed the link between mtDNA common deletion rate and energy Notes: Values are expressed as mean ± Standard deviation * median (minimum-maximum). When groups were evaluated in terms of progress, no significant difference was found in all three groups (p ¼ 0.959, 0.594, and 0.173, respectively).…”

Section: Discussionmentioning

confidence: 99%

“…Creatine has been reported to have antiinflammatory, antioxidant effects and it has been shown that it acts as a free radical scavenger. [4][5][6][7][8] Besides this, recent reports supported that Cr has additional beneficial effects on various neurological, muscular, cardiovascular disorders, and aging. [9][10][11][12][13][14] The aim of this study is to investigate the possible protective effect of creatine therapy on cisplatin-induced nephrotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Effect of free creatine therapy on cisplatin-induced renal damage

et al. 2014

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Cisplatin is one of the commonly used anticancer drugs and nephrotoxicity limits its use. The aim of this study is to investigate the possible protective effect of creatine supplementation on cisplatin-induced nephrotoxicity. Sixty male Sprague-Dawley rats were divided into three groups: Group I: Cisplatin (n ¼ 20) (7 mg/kg cisplatin intraperitoneal (i.p.) single dose), group II: Cisplatin + creatine monohydrate (n ¼ 20) (7 mg/kg cisplatin i.p. single dose and 300 mg/kg creatine p.o. daily for 30 days starting on first day of cisplatin injection), group III: Control group (n ¼ 20) (Serum physiologic, 2.5 mL/kg i.p.). Sacrifications were performed at first week and 30th day. Blood urea nitrogen (BUN) and serum creatinine levels, histopathological evaluation, mitochondrial deoxyribonucleic acid (mtDNA) common deletion rates, and body weights of rats were evaluated. A significant decrease in body weight, higher values of kidney function tests, histopathological scores, and mtDNA deletion ratios were observed in group I compared to control group at days 7 and 30 (p50.05). In group II, there was a slight decrease in body weight at same days (p ¼ 0.931 and 0.084, respectively). Kidney function tests, histopathological scores, and mtDNA common deletion ratios were statistically better in group II than group I at 7th and 30th day (p50.05). Although creatine significantly reversed kidney functions and pathological findings, this improvement was not sufficient to reach normal control group's results at days 7 and 30. In conclusion, the present study demonstrates that creatine administration is a promising adjuvant protective drug for reducing nephrotoxic effect of cisplatin.

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Anti‐inflammatory activity of creatine supplementation in endothelial cells in vitro

Cited by 64 publications

References 33 publications

Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A1 and A2A receptor activation

Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A1 and A2A receptor activation

Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity

Effect of free creatine therapy on cisplatin-induced renal damage

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