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Therapeutic potential of 7,8-dimethoxycoumarin on cisplatin- and ischemia/reperfusion injury-induced acute renal failure in rats

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Abstract

This study was designed to investigate the role of 7,8-dimethoxycoumarin on cisplatin- and ischemia/reperfusion (I/R)-induced acute renal failure in rats. Acute renal failure was induced in rats by administration of a single dose of cisplatin (CP) (6 mg/kg, intraperitoneally on day 6) and occlusion of the left renal artery for 45 min (I) and opened for the next 24 h (R). The drug samples of 7,8-dimethoxycoumarin (DMC, 50, 75, and 100 mg/kg) and cyclosporin A (50 μM/kg) were administered orally for six consecutive days. Administration of a single dose of cisplatin and I/R event has significantly raised blood urea nitrogen and creatinine, N-acetyl beta-d-glucosaminidase, and thiobarbituric acid reactive substances but decreased FrNa, creatinine clearance, reduced glutathione (GSH), mitochondrial cytochrome c oxidase, and adenosine triphosphate levels. Further, pretreatment of DMC (50, 75, and 100 mg/kg, p.o., for six consecutive days) has ameliorated the CP- and I/R-induced biochemical and histopathological changes in a dose-dependent manner. Furthermore, 75 and 100 mg/kg of 7,8-dimethoxycoumarin has shown to possess the significant renoprotective effect similar to that of the cyclosporin A-treated group which served as positive control. Based on the results of the present study, it has been concluded that 7,8-dimethoxycoumarin protects the kidney against the CP and I/R injury via antioxidant, anti-inflammatory, and inactivation of mitochondrial permeability transition pore opening.

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Acknowledgments

Thanks to all the faculty members of Rayat Institute of Pharmacy for their encouragement and support. We are also grateful to Rayat and Bahra Educational and Research Trust for their unconditional help to carry out this project.

Conflict of interest

There was no conflict of interest in the present study.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Rayat Institute of Pharmacy, Near Railmajra, Ropar, 144533, Punjab, India

    Arunachalam Muthuraman, Shailja Sood, Karan Deep Singh Puri, Anil Peters, Ashish Chauhan, Pradeep Kumar Arora & Ajay Rana

  2. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, Punjab, India

    Arunachalam Muthuraman

  3. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, 160062, Punjab, India

    Muthusamy Ramesh

  4. Department of Pharmaceutical Sciences, Lovely Professional University, Jalandhar, 144402, Punjab, India

    Ashish Chauhan & Pradeep Kumar Arora

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  1. Arunachalam Muthuraman
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Correspondence to Arunachalam Muthuraman.

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Muthuraman, A., Sood, S., Ramesh, M. et al. Therapeutic potential of 7,8-dimethoxycoumarin on cisplatin- and ischemia/reperfusion injury-induced acute renal failure in rats. Naunyn-Schmiedeberg's Arch Pharmacol 385, 739–748 (2012). https://doi.org/10.1007/s00210-012-0751-1

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