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Cyclophosphamide-induced nephrotoxicity, genotoxicity, and damage in kidney genomic DNA of Swiss albino mice: the protective effect of Ellagic acid

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Abstract

Cyclophosphamide (CPM), an alkylating agent is used as an immunosuppressant in rheumatoid arthritis and in the treatment of several cancers as well. In this study, Ellagic acid (EA), a naturally occurring plant polyphenol, was evaluated for its antigenotoxicity and antioxidant efficacy against the CPM-induced renal oxidative stress and genotoxicity in Swiss albino mice. The mice were given a prophylactic treatment of EA orally at a dose of 50 and 100 mg/kg body weight (b wt) for seven consecutive days before the administration of a single intraperitoneal (i.p.) injection of CPM at 50 mg/kg b wt. The modulatory effects of EA on CPM-induced nephrotoxicity and genotoxicity were investigated by assaying oxidative stress biomarkers, serum kidney toxicity markers, DNA fragmentation, alkaline unwinding assay, micronuclei (MN) assay, and by histopathological examination of kidney tissue. A single intraperitoneal administration of CPM in mice increased malondialdehyde level with depletion in glutathione content, antioxidant enzymes activities, viz. glutathione peroxidase, glutathione reductase, catalase, quinone reductase, induced DNA strand breaks, and MN induction. EA oral administration at both doses caused significant reduction in their levels, restoration in the activities of antioxidant enzymes, reduction in MN formation, and DNA fragmentation. Serum toxicity marker enzymes like BUN, creatinine, and LDH were also increased after CPM treatment which was significantly decreased in EA pretreated groups. Present findings suggest a prominent role of EA against CPM-induced renal injury, DNA damage, and genotoxicity.

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Abbreviations

EA:

Ellagic acid

CPM:

Cyclophosphamide

GSH:

Reduced glutathione

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

XO:

Xanthine oxidase

MDA:

Malondialdehyde

BUN:

Blood urea nitrogen

LDH:

Lactate dehydrogenase

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Acknowledgment

The authors are thankful to CCRUM (AYUSH), Ministry of Health and Family Welfare, Govt. of India for providing funds to carry out this research.

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Authors and Affiliations

  1. Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India

    Muneeb U. Rehman, Mir Tahir, Farrah Ali, Wajhul Qamar, Abdul Lateef, Rehan Khan, Abdul Quaiyoom,  Oday-O-Hamiza & Sarwat Sultana

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  1. Muneeb U. Rehman
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  2. Mir Tahir
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  3. Farrah Ali
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  4. Wajhul Qamar
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Correspondence to Sarwat Sultana.

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Rehman, M.U., Tahir, M., Ali, F. et al. Cyclophosphamide-induced nephrotoxicity, genotoxicity, and damage in kidney genomic DNA of Swiss albino mice: the protective effect of Ellagic acid. Mol Cell Biochem 365, 119–127 (2012). https://doi.org/10.1007/s11010-012-1250-x

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  • DOI: https://doi.org/10.1007/s11010-012-1250-x

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