Systemic study of selected HDAC inhibitors in cardiac complications associated with cancer cachexia

Can J Physiol Pharmacol. 2021 Oct 6. doi: 10.1139/cjpp-2021-0012. Online ahead of print.ABSTRACTCancer cachexia is mainly characterized by wasting of skeletal muscles, fat and body weight loss, along with severe complications of major organs like liver, heart, brain and bone. There can be diminishing performance of these major organs as cancer cachexia progresses, one such drastic effect on the cardiac system. In present study, differential effect of histone deacetylase inhibitors (HDACi) on cardiac complications associated with cancer cachexia is studied. Two models were used to induce cancer cachexia: B16F1 induced metastatic cancer cachexia and LLC induced cancer cachexia. Potential of Class I HDAC inhibitor Entinostat, Class II HDAC inhibitor MC1568 and non-specific HDAC inhibitor sodium butyrate on cardiac complications were evaluated using the cardiac hypertrophy markers, hemodynamic markers and cardiac markers along with histopathological evaluation of heart sections by periodic acid schiff staining, masson trichrome staining, picro sirius red staining and haematoxylin and eosin staining. Immunohistochemistry evaluation by vimentin and caspase 3 protein expression was evaluated. Entinostat showed promising results by attenuating the cardiac complications, MC1568 treatment further exacerbated the cardiac complications while non-conclusive effect were recorded after treatment with sodium butyrate. Further, this study will be helpful in evaluating other HDAC inhibitors fo...
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research