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环境病理学,毒理学和肿瘤学期刊
影响因子: 1.241 5年影响因子: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN 打印: 0731-8898
ISSN 在线: 2162-6537

环境病理学,毒理学和肿瘤学期刊

DOI: 10.1615/JEnvironPatholToxicolOncol.2016013997
pages 249-262

Naringenin Ameliorates Doxorubicin Toxicity and Hypoxic Condition in Dalton's Lymphoma Ascites Tumor Mouse Model: Evidence from Electron Paramagnetic Resonance Imaging

Venkatesan Kathiresan
School of Biological Sciences, Madurai Kamaraj University, Madurai-625 021, India; School of Chemistry, Madurai Kamaraj University, Madurai-625 021, India
Swathika Subburaman
School of Biological Sciences, Madurai Kamaraj University, Madurai-625 021, India
Arun Venkatesh Krishna
University Science Instrumentation Centre, Madurai Kamaraj University, Madurai-625 021, India
Mathivanan Natarajan
University Science Instrumentation Centre, Madurai Kamaraj University, Madurai-625 021, India
Gandhidasan Rathinasamy
School of Chemistry, Madurai Kamaraj University, Madurai-625 021, India
Kumaresan Ganesan
School of Biological Sciences, Madurai Kamaraj University, Madurai-625 021, India
Murugesan Ramachandran
School of Biological Sciences, Madurai Kamaraj University, Madurai-625 021, India; School of Chemistry, Madurai Kamaraj University, Madurai-625 021, India; Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Kelambakkam, Chennai-603 103, India

ABSTRACT

Doxorubicin (DOX) is a well-known cytotoxic agent used extensively as a chemotherapeutic drug to eradicate a wide variety of human cancers. Reactive oxygen species (ROS)-mediated oxidative stress during DOX treatment can induce cardiac, renal, and hepatic toxicities, which can constrain its use as a potential cytotoxic agent. The present work investigates the antioxidant potential of naringenin (NAR) against DOXinduced toxicities of a Dalton's lymphoma ascites (DLA) tumor-bearing mouse model. Mice were randomized into four groups: a negative control, positive control, DOX (2.5 mg/kg) treated, and DOX (2.5 mg/kg) + NAR (50 mg/kg/d) treated. DOX administration significantly altered the levels of functional markers in blood and antioxidant enzymes in kidney, heart, lung, liver, spleen, and tumor tissues. These changes in antioxidant enzymes and successive lipid peroxidation were prevented by NAR supplementation, resulting in decreases in the risk of toxicity due to DOX therapy. Histopathology results and electron paramagnetic resonance imaging (EPRI) of the tumor microenvironment confirmed this evidence. Using EPRI, pharmacokinetics of the nitroxide, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (3-CP) was monitored intratumorally before and after chemotherapy. EPRI of the DOX + NAR–treated mouse model showed reduced tumor size with significant modification of the hypoxic condition inside the tumor microenvironment. Consequently, these findings suggest that NAR treatment significantly reduces DOX-induced toxicity and the hypoxic condition in a DLA tumor-bearing mouse model.