Elucidating the interplay of PPAR gamma inhibition and energy demand in adriamycin-induced cardiomyopathy: In Vitro and In Vivo perspective
- Title
- Elucidating the interplay of PPAR gamma inhibition and energy demand in adriamycin-induced cardiomyopathy: In Vitro and In Vivo perspective
- Creator
- Seenivasan K.; Arunachalam S.; Tirupathi Pichiah P.B.; Vasan S.B.; Venkateswaran M.R.; Siva D.; Gothandam J.; Achiraman S.
- Description
- Adriamycin is an anticancer anthracycline drug that inhibits the progression of topoisomerase II activity and causes apoptosis. The effective clinical application of the drug is very much limited by its adverse drug reactions on various tissues. Most importantly, Adriamycin causes cardiomyopathy, one of the life-threatening complications of the drug. Altered expression of PPAR? in adipocytes inhibited the glucose and fatty acids uptake by down regulating GLUT4 and CD36 expression and causes cardiotoxicity. Therefore, the influence of Adriamycinin cardiac ailments was investigated in vivo and in vitro. Adriamycin treated rats showed altered ECG profile, arrhythmic heartbeat with the elevated levels of CRP and LDH. Dysregulated lipid profiles with elevated levels of cholesterol and triglycerides were also observed. Possibilities of cardiac problems due to cardiomyopathy were analyzed through histopathology. Adriamycin treated rats showed no signs for atheromatous plaque formation in aorta but disorganized cardiomyocytes with myofibrillar loss and inflammation in heart tissue, indicative of cardiomyopathy. Reduced levels of antioxidant enzymes confirmed the incidence of oxidative stress. Adriamycin treatment significantly reduced glucose and insulin levels, creating energy demand due to decreased glucose and insulin levels with increased fatty acid accumulation, ultimately resulting in oxidative stress mediated cardiomyopathy. Since PPARs play a vital role in regulating oxidative stress, the effect of Adriamycin on PPAR? was analyzed by western blot. Adriamycin downregulated PPAR? in a dose-dependent manner in H9C2 cells in vitro. Overall, our study suggests that Adriamycin alters glucose and lipid metabolism via PPAR? inhibition that leads to oxidative stress and cardiomyopathy that necessitates a different therapeutic approach. 2024 Wiley Periodicals LLC.
- Source
- Journal of Biochemical and Molecular Toxicology, Vol-38, No. 10
- Date
- 2024-01-01
- Publisher
- John Wiley and Sons Inc
- Subject
- Adriamycin; cancer; cardiotoxicity; oxidative stress; PPAR?
- Coverage
- Seenivasan K., Department of Environmental Biotechnology, Bharathidasan University, Tamil Nadu, Tiruchirappalli, India; Arunachalam S., Department of Life Sciences, School of Sciences, CHRIST University, Karnataka, Bengaluru, India; Tirupathi Pichiah P.B., Department of Environmental Biotechnology, Bharathidasan University, Tamil Nadu, Tiruchirappalli, India; Vasan S.B., School of Life Sciences, Bharathidasan University, Tamil Nadu, Tiruchirappalli, India; Venkateswaran M.R., Department of Environmental Biotechnology, Bharathidasan University, Tamil Nadu, Tiruchirappalli, India; Siva D., Centre for Laboratory Animal Technology and Research, Sathyabama Institute of Science and Technology, Tamil Nadu, Chennai, India; Gothandam J., Department of Environmental Biotechnology, Bharathidasan University, Tamil Nadu, Tiruchirappalli, India; Achiraman S., Department of Environmental Biotechnology, Bharathidasan University, Tamil Nadu, Tiruchirappalli, India
- Rights
- Restricted Access
- Relation
- ISSN: 10956670; PubMed ID: 39328005; CODEN: JBMTF
- Format
- Online
- Language
- English
- Type
- Article
Collection
Citation
Seenivasan K.; Arunachalam S.; Tirupathi Pichiah P.B.; Vasan S.B.; Venkateswaran M.R.; Siva D.; Gothandam J.; Achiraman S., “Elucidating the interplay of PPAR gamma inhibition and energy demand in adriamycin-induced cardiomyopathy: In Vitro and In Vivo perspective,” CHRIST (Deemed To Be University) Institutional Repository, accessed February 24, 2025, https://archives.christuniversity.in/items/show/12808.