title: Robinin modulates doxorubicin-induced cardiac apoptosis by TGF-β1 signaling pathway in Sprague Dawley rats.
abstract: The study focussed on the cardioprotective effect of robinin on doxorubicin-induced cardio-toxicity in Sprague Dawley rats. After the experimental period, animals were sacrificed and the various parameters such as cardiac markers, toxicity parameters, antioxidant status, ROS generation, lipid peroxidation status and inflammatory parameters were assessed. Gene expression study by RT-PCR analysis and proteins expression study by western blotting were done. Doxorubicin causes significant increase in the levels of cardiac marker enzymes, namely lactate dehydrogenase (LDH), creatine phospokinase (CPK), toxicity parameters like serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT). Antioxidant enzyme levels were decreased; lipid peroxidation products in heart tissue and inflammatory markers, namely cyclooxygenase (COX2) and lipooxygenase (LOX15) were significantly increased. Gene expression study by RT-PCR analysis of transforming growth factor-β1 (TGF-β1), Smad2, murine double minute (Mdm2), Smad3, cyclin-dependent kinase inhibitor 2A (CDKN2A), Smad4 and Smad7 were significantly altered. The western blotting study of p53, Bcl-2 and Bax also showed altered expression. The supplementation of the Robinin along with DOX caused normalised level of all the above parameters and cardio-toxicity. This study revealed the cardioprotective nature of Robinin on doxorubicin-induced cardiac toxicity by modulating TGF-β1 signaling pathway in Sprague Dawley rats.
authors.affiliation: Department of Biochemistry, School of Life sciences, University of Kerala, Thiruvananthapuram, Kariavattom Campus, 695 581, Kerala, India.
authors.forename: P A
authors.initials: PA
authors.lastname: Janeesh
authors.affiliation: Department of Biochemistry, School of Life sciences, University of Kerala, Thiruvananthapuram, Kariavattom Campus, 695 581, Kerala, India. Electronic address: annieab2013@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Abraham
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005419:Flavonoids / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D053773:Transforming Growth Factor beta1; C005183:robinin; D004317:Doxorubicin
keywords: Cardiac markers; Cardiac toxicity; Doxorubicin; Robinin