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Journal of Environmental Pathology, Toxicology and Oncology
IF: 1.241 5-Year IF: 1.349 SJR: 0.519 SNIP: 0.613 CiteScore™: 1.61

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2017017087
pages 121-130

Insulin Protects against Brain Oxidative Stress with an Apparent Effect on Episodic Memory in Doxorubicin-Induced Cognitive Dysfunction in Wistar Rats

Grandhi Venkata Ramalingayya
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal–576104, Karnataka, India; Discovery Biology, Suven Life Sciences Ltd., Hyderabad, Telangana, India
Vishwajeet Sonawane
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal-576104, Karnataka, India
Sri Pragnya Cheruku
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal-576104, Karnataka, India
Anoop Kishore
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal – 576104, Karnataka, India
Pawan G. Nayak
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal – 576104, Karnataka, India
Nitesh Kumar
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal-576104, Karnataka, India
Rekha S. Shenoy
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal-576104, Karnataka, India
Krishnadas Nandakumar
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal – 576104, Karnataka, India

ABSTRACT

The present study was aimed at assessing the protective effect of insulin against doxorubicin (DOX)-induced cognitive dysfunction in Wistar rats. Cognitive function for episodic memory was assessed by a novel object recognition task (NORT) in male Wistar rats. Oxidative stress markers−SOD, catalase, glutathione, and lipid peroxidation−in the hippocampus and frontal cortex were assessed using colorimetric methods. Doxorubicin treatment (2.5 mg/kg, i.p., every 5 days for 50 days) reduced recognition and discriminative indices in NORT with increased oxidative stress in the brain. A nonhypoglycemic dose of insulin (0.5 IU/kg, i.p.) significantly reduced brain oxidative stress (MDA) induced by doxorubicin with an increase in the antioxidant defense systems (SOD, catalase, and GSH). Rats treated with combined insulin and DOX spent comparatively more time with the novel object when compared to the non-novel objects; however, the observed difference was not statistically significant. An apparent improvement (p < 0.26) in recognition of the novel object was observed against the damage induced by doxorubicin. These results suggest that insulin reduces brain oxidative stress and apparently improves doxorubicin-induced cognitive dysfunction in Wistar rats.


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