title: Tangeretin ameliorates oxidative stress in the renal tissues of rats with experimental breast cancer induced by 7,12-dimethylbenz[a]anthracene.
abstract: Tangeretin, a citrus polymethoxyflavone, is an antioxidant modulator which has been shown to exhibit a surfeit of pharmacological properties. The present study was hypothesized to explore the therapeutic activity of tangeretin against 7,12-dimethylbenz[a]anthracene (DMBA) induced kidney injury in mammary tumor bearing rats. Recently, we have reported the chemotherapeutic effect of tangeretin in the breast tissue of DMBA induced rats. Breast cancer was induced by "air pouch technique" with a single dose of 25mg/kg of DMBA. Tangeretin (50mg/kg/day) was administered orally for four weeks. The renoprotective nature of tangeretin was assessed by analyzing the markers of oxidative stress, proinflammatory cytokines and antioxidant competence in DMBA induced rats. Tangeretin treatment revealed a significant decline in the levels of lipid peroxides, inflammatory cytokines and markers of DNA damage, and a significant improvement in the levels of enzymatic and non-enzymatic antioxidants in the kidney tissue. Similarly, mRNA, protein and immunohistochemical analysis substantiated that tangeretin treatment notably normalizes the renal expression of Nrf2/Keap1, its downstream regulatory proteins and the inflammatory cytokines in the DMBA induced rats. Histological and ultrastructural observations also evidenced that the treatment with tangeretin effectively protects the kidney from DMBA-mediated oxidative damage, hence, proving its nephroprotective nature.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu 600025, India.
authors.forename: Arivazhagan
authors.initials: A
authors.lastname: Lakshmi
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu 600025, India. Electronic address: subbus2020@yahoo.co.in.
authors.forename: Sorimuthu Pillai
authors.initials: SP
authors.lastname: Subramanian
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001551:Benz(a)Anthracenes / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D016207:Cytokines / Q000032:analysis; D005260:Female; D047309:Flavones / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000032:analysis; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000187:drug effects; D009569:Nitric Oxide / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000032:analysis; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D001551:Benz(a)Anthracenes; D002273:Carcinogens; D016207:Cytokines; D047309:Flavones; D051267:NF-E2-Related Factor 2; D013481:Superoxides; C046810:7,12-dihydroxymethylbenz(a)anthracene; D009569:Nitric Oxide; D017665:Hydroxyl Radical; C059006:tangeretin
keywords: DMBA; Inflammatory cytokines; Nephrotoxicity; Nrf2–Keap1 pathway; Oxidative stress; Tangeretin