curcumin and Hypertrophy--Right-Ventricular

This study investigates the therapeutic effect of a nanocurcumin formulation (NCF) containing nanocurcumin (NC) and pyrroloquinoline quinone (PQQ) on ameliorating hypoxia-induced stress in hypertrophied primary human ventricular cardiomyocytes (HVCM) under hypoxic conditions, as validated in a Sprague-Dawley rat model of chronic hypobaric hypoxia (cHH)-induced right ventricular hypertrophy (RVH). Based on our previous findings, here, we analyzed the improvement in the protective efficacy of NCF against mitochondrial damage. The electron transport chain Complexes' activities were analyzed as a chief operational center for mitochondrial homeostasis, along with key gene and protein markers for mitochondrial biogenesis, redox function, fatty acid oxidation, bio-energetic deficit and cell survival. NCF supplementation imparts cyto-protection from hypoxia-induced hypertrophy and damage in both in vitro and in vivo models while maintaining mitochondrial homeostasis better than NC and PQQ alone. This study proposes the use of NCF as a potential candidate molecule for imparting protection from high altitude-induced maladies in ascendants.

Topics: Animals; Cell Survival; Cells, Cultured; Curcumin; Hypertrophy; Hypertrophy, Right Ventricular; Hypoxia; Male; Mitochondria; Myocytes, Cardiac; Pyrroles; Quinolines; Rats; Rats, Sprague-Dawley

Topics: Acclimatization; Altitude Sickness; Animals; Antioxidants; Apoptosis; Curcumin; Hypertrophy, Right Ventricular; Male; Nanostructures; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Signal Transduction

The present study is an attempt to leverage therapeutic benefits of curcumin in pulmonary hypertension by encapsulating it in biodegradable poly(lactide-co-glycolic) acid nanoparticles. Pulmonary hypertension is induced in experimental animals by subjecting them to chronic hypoxic conditions. The ability of curcumin encapsulated nanoparticles to manage pulmonary hypertension is measured by right ventricular hypertrophy, haematocrit, vascular remodelling and target tissue levels of curcumin. Further, single oral dose tissue distribution of the nanoparticulate curcumin was also assessed under normoxic and hypoxic conditions. Orally administered nanoparticulate curcumin failed to offer any protection against hypoxia induced pulmonary hypertension as indicated by insignificant changes in right ventricular hypertrophy and vascular remodelling that are similar to untreated groups. A significant difference in the target tissue levels was observed between normoxic vs. hypoxic rats. The study suggests that hypoxia has a major role in the particle localization in lungs probably due to the altered blood flow, increased barrier properties of the lung vasculature and decreased endocytosis. The target tissue levels of curcumin under hypoxia are much lower to that achieved in normoxic rats probably due to difference in particle dynamics, resulting in the failure of treatment.

Topics: Administration, Oral; Animals; Curcumin; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Lactic Acid; Lung; Male; Nanoparticles; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Tissue Distribution