title: Nordihydroguaiaretic acid ameliorates cisplatin induced nephrotoxicity and potentiates its anti-tumor activity in DMBA induced breast cancer in female Sprague-Dawley rats.
abstract: Cisplatin is a widely used antineoplastic drug, but its clinical usefulness is limited due to dose dependent nephrotoxicity. Nordihydroguaiaretic acid (NDGA) is a natural compound with broad pharmacological properties like antioxidant, anti-inflammatory and anticancer activity. The present study was undertaken to evaluate the possible beneficial effects of NDGA on cisplatin induced nephrotoxicity as well as its anticancer activity in rats bearing DMBA induced mammary tumors. The effect of NDGA on cisplatin induced nephrotoxicity was evaluated by checking serum nephrotoxicity markers, antioxidant enzymes and inflammatory markers level and kidney histopathology. NDGA induced amelioration of cisplatin nephrotoxicity was clearly visible from significant reductions in serum blood urea nitrogen (86.51 g/dl) and creatinine (5.30 g/dl) levels and significant improvement in body weight change (-10.34 g) and kidney weight (728 mg/kg). The protective effect of NDGA against cisplatin induced nephrotoxicity in the rats was further confirmed by significant restoration of antioxidant enzymes like SOD (86.28% inhibition), inflammatory markers like TNF-α (34.6 pg/ml) and histopathological examination. Moreover, our results showed that NDGA potentiated anti-breast cancer activity of cisplatin through an increment in the expression of antioxidant enzymes like SOD (85.35% inhibition) in breast cancer tissue. These results indicated that NDGA potentiated the anti-breast cancer activity of cisplatin, which was clearly evident from the tumor volume and % tumor inhibition in breast cancer rats. The current study demonstrated that NDGA may modify the therapeutic effect of cisplatin in DMBA induced breast cancer in female Sprague-Dawley rats.
authors.affiliation: Laboratory of Molecular Pharmacology and Toxicology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Guwahati, GMC 3rd floor, Bhangagarh, Guwahati 781032, Assam, India. Electronic address: mundhenitin2@gmail.com.
authors.forename: Nitin Arunrao
authors.initials: NA
authors.lastname: Mundhe
authors.affiliation: Laboratory of Molecular Pharmacology and Toxicology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Guwahati, GMC 3rd floor, Bhangagarh, Guwahati 781032, Assam, India.
authors.forename: Parveen
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Laboratory of Molecular Pharmacology and Toxicology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Guwahati, GMC 3rd floor, Bhangagarh, Guwahati 781032, Assam, India.
authors.forename: Sahabuddin
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Laboratory of Molecular Pharmacology and Toxicology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Guwahati, GMC 3rd floor, Bhangagarh, Guwahati 781032, Assam, India.
authors.forename: Vinayak
authors.initials: V
authors.lastname: Jamdade
authors.affiliation: Department of Medicine, B.J. Medical College and Hospital, Pune 413102, Maharashtra, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mundhe
authors.affiliation: Laboratory of Pharmacology, Department of Pharmacology, GMC 3rd Floor, Bhangagarh, Guwahati 781032, Assam, India.
authors.forename: Mangala
authors.initials: M
authors.lastname: Lahkar
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009637:Masoprocol / Q000008:administration & dosage / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D015127:9,10-Dimethyl-1,2-benzanthracene; D009637:Masoprocol; D003404:Creatinine; D002374:Catalase; D013482:Superoxide Dismutase; D002945:Cisplatin
keywords: Anticancer; Antioxidant; Cisplatin; NDGA; Nephrotoxicity