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.

Chemoprotective Activity of Oroxylum Indicum Vent. Root Bark Against Cyclophosphamide Mediated Myelosuppression and Organ Injury.

“…Chrysin (Pushpavalli et al, 2010, Veerappan andSenthilkumar, 2015), biochanin-A (Zhang et al, 2011) and ellagic acid (Warpe et al, 2015a) are compounds attributed with anti-oxidant properties. There are proven studies of chemoprotective properties of ellagic acid (Rehman et al, 2012, Warpe et al, 2015b. It is hence, conclusive that the presence of anti-oxidant compounds in the OIM extract may possibly have mediated the chemoprotective effects, through their combined action.…”

Protective Effect of Elaeagnus angustifolia L. Fruit Hydroalcoholic Extract on Cyclophosphamide-Induced Nephrotoxicity in Mice

“…An oxidative stress was formulated from a disturbance between the generation of reactive oxygen species (ROS) and their elimination through antioxidant systems. The GSH either can be regarded as a non-enzymatic anti-oxidant through interplaying between ROS and SH group or may be implicated in the enzymatic detoxification response for ROS as a cofactor (22). The MDA, an indicator of oxidative damage, increases in body after injection of CP, resulting in the ultimate damage to membrane lipids with the creation and diffusion of free radicals and raised uptake of oxygen, leading to the transformation of the double bonds in unsaturated lipid.…”

Ameliorative effects of hydroalcoholic extract of Lavandula officinalis L. on cyclophosphamide-induced nephrotoxicity in mice

“…It is a well-known bi-function alkylating agent that transfer alkyl residues into a covalent bond with DNA widely used in cancer chemotherapy and expresses its genotoxicity when metabolically activated (36). Normal tissues injury or damage is the major limitation of using CP, which gives rise to numerous side effects, CP treatment also results in the production of ROS, which cause peroxidative damage to kidney and other vital organ (37). A number of studies has been reported that CP or its metabolites leads to acute inflammation of the urinary bladder (cystitis), renal damage and liver damage, thereby limiting the therapeutic use of the drug (38).…”