Protective effects of pioglitazone on renal ischemia-reperfusion injury in mice

Hu, Honglin; Zou, Cong; Xi, Xiaoqing; Shi, Ziming; Wang, Gongxian; Huang, Xueming

doi:10.1016/j.jss.2012.01.012

Cited by 29 publications

(24 citation statements)

References 21 publications

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“…Amylase in lethal acute pancreatitis measured more than 12,000 U/L, higher than an 8-fold elevation compared with our CLP mice (30). In our current study, BUN levels of 90 mg/dL approached those seen in a lethal model of renal ischemia-reperfusion injury of about 98 mg/dL at 24 h (31). There may be progressive organ injury closer to death, and the measurements for cystatin C indicated that more significant kidney injury did develop in 24 h before death in nonsurviving mice.…”

Section: Discussionsupporting

confidence: 64%

Early Murine Polymicrobial Sepsis Predominantly Causes Renal Injury

Craciun

Iskander

Chiswick³

et al. 2014

Shock

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Multiple organ failure in sepsis substantially increases mortality. This study examined if there was greater hepatic, pancreatic, splenic, or renal injury in mice that would die during sepsis induced by cecal ligation and puncture (CLP) compared with that of those that would survive. Mice were stratified into groups predicted to die (Die-P) or predicted to live (Live-P) in the first 5 days after CLP based on plasma interleukin 6 levels. Groups were sacrificed to harvest organs for histology. Separate animals were followed for survival with daily blood sampling to examine renal function. No significant histological evidence of organ injury was observed in either the Live-P or Die-P mice. Minimal hepatic injury occurred as plasma aspartate transaminase demonstrated less than a 2-fold increase over normal in both groups. In addition, pancreatic injury was minimal as there was also less than a 2-fold increase in plasma amylase levels. In contrast, blood urea nitrogen levels were nearly five times higher within 24 h in Die-P mice compared with those of mice predicted to live. Mice with blood urea nitrogen levels higher than 44 mg/dL had a 17.6 higher relative risk of dying (95% confidence interval, 4.5–69.4). Cystatin C, a more specific kidney function biomarker, was also elevated at 24 h after CLP. When the cystatin C levels were analyzed relative to the hours before death, rather than hours after CLP, they were also significantly increased in mice Dead by day 5 compared with those Alive after day 5. We conclude that limited liver, pancreas, and spleen injury develops during murine CLP-induced sepsis while significant kidney injury is present. The renal injury becomes worse closer to death.

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Section: Discussionsupporting

confidence: 64%

Early Murine Polymicrobial Sepsis Predominantly Causes Renal Injury

Craciun

Iskander

Chiswick³

et al. 2014

Shock

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“…7 Wei et al 40 reported that cisplatininduced apoptosis was attenuated in the Bax protein-deficient mice and authors showed Bax protein and cisplatin-induced apoptosis association. In a renal ischemia-reperfusion injury animal model, Hu et al 15 reported that pioglitazone pretreatment provide up-regulation of expression of Bcl-2 proteins and down-regulation of expression of Bax protein in kidney. Through this way mitochondrial activity and cell integrity are maintained.…”

Section: Discussionmentioning

confidence: 99%

“…Along with its anti-inflammatory and antioxidant effects, pioglitazone has been reported to have protective effects on cerebral, myocardial and renal ischemia. [10][11][12][13][14][15] Real-time cell analyzer (RTCA) system is a label-free and non-invasive method which works with the basis of measurement of the electrical impedance on integrated microelectrodes in microwell plates. After the interaction of cells with electrodes, ionic environments alter and modifying impedance is determined in each well by RTCA system.…”

Section: Introductionmentioning

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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“…Today the therapeutic effects of peroxisome proliferator activated receptor gamma (PPAR-γ) ligands, including pioglitazone, have reached far beyond their use as insulin-sensitizers, where they exert beneficial effects in conditions associated with I/R, including the kidney [27], [28]. The PPAR-γ role relies on the modulation of several I/R-connected markers, viz., apoptosis, caspase-1, NF-κB and its downstream target genes TNF-α, ICAM-1, and iNOS [28], [29].…”

Section: Introductionmentioning

confidence: 99%

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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Protective effects of pioglitazone on renal ischemia-reperfusion injury in mice

Cited by 29 publications

References 21 publications

Early Murine Polymicrobial Sepsis Predominantly Causes Renal Injury

Early Murine Polymicrobial Sepsis Predominantly Causes Renal Injury

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

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

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