title: Cyclophosphamide-induced nephrotoxicity, genotoxicity,  and damage in kidney genomic DNA of Swiss albino mice:  the protective effect of Ellagic acid.
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.
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Muneeb U
authors.initials: MU
authors.lastname: Rehman
authors.forename: Mir
authors.initials: M
authors.lastname: Tahir
authors.forename: Farrah
authors.initials: F
authors.lastname: Ali
authors.forename: Wajhul
authors.initials: W
authors.lastname: Qamar
authors.forename: Abdul
authors.initials: A
authors.lastname: Lateef
authors.forename: Rehan
authors.initials: R
authors.lastname: Khan
authors.forename: Abdul
authors.initials: A
authors.lastname: Quaiyoom
authors.lastname: Oday-O-Hamiza
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D003520:Cyclophosphamide / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D004610:Ellagic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D004912:Erythrocytes / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000975:Antioxidants; D004610:Ellagic Acid; D003520:Cyclophosphamide; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D005978:Glutathione