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Pioglitazone ameliorates renal ischemia reperfusion injury through NMDA receptor antagonism in rats

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Abstract

The present study investigated the role of N-methyl-d-aspartate (NMDA) receptors in pioglitazone-mediated protection against renal ischemia reperfusion injury (IRI) in rats. Male wistar rats were subjected to 40 min of bilateral renal ischemia followed by reperfusion for 24 h to induce kidney injury. The renal damage was evaluated by measuring serum creatinine, creatinine clearance, blood urea nitrogen, uric acid, electrolytes, and microproteinuria in rats. Oxidative stress in renal tissues was quantified in terms of myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione level. Hematoxylin–eosin and periodic acid Schiff staining of renal tissues were performed to observe histological changes. Pioglitazone (20 and 40 mg/kg) was administered 1 h prior to ischemia in rats. In separate groups, NMDA agonists, glutamic acid (200 mg/kg), and spermidine (20 mg/kg) were administered 1 h prior to pioglitazone treatment, followed by renal IRI in rats. Ischemia reperfusion resulted in marked renal damage with significant changes in serum and urine parameters along with marked oxidative stress and histological changes in kidneys. Pioglitazone treatment afforded anti-oxidant effect and renoprotection in a dose-dependent manner in rats. Pioglitazone-mediated renoprotection was attenuated by glutamic acid and spermidine pretreatment in rats, which indicated the role of NMDA receptors in pioglitazone-mediated protection. It is concluded that NMDA antagonism serves as one of the mechanisms in pioglitazone-mediated protection against renal IRI in rats.

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Author’s contribution

APS, NS, and PMSB conceived and designed the project. APS did pharmacological treatments and performed surgery and biochemical studies. APS, NS, and PMSB analyzed the data and wrote manuscript. All authors approved the manuscript before submission to journal.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India

    Amrit Pal Singh & Preet Mohinder Singh Bedi

  2. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India

    Nirmal Singh

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Correspondence to Preet Mohinder Singh Bedi.

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Singh, A.P., Singh, N. & Bedi, P.M.S. Pioglitazone ameliorates renal ischemia reperfusion injury through NMDA receptor antagonism in rats. Mol Cell Biochem 417, 111–118 (2016). https://doi.org/10.1007/s11010-016-2718-x

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  • DOI: https://doi.org/10.1007/s11010-016-2718-x

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