Cardioprotective Effect of Idebenone Nanoparticles in Doxorubicin Induced Cardiomyopathy in Rats: Assessment of Myocardial Performance, Haemapoietic Parameters and Immunological Changes

Abstract

Doxorubicin (DXR) is an anthracycline anti-neoplastic agent associated with severe cardiotoxicity. Idebenone has recently been shown to exhibit promising results in improving cardiac performance. The objective of the present study was to develop nanoparticles of idebenone and investigate its cardioprotective effect in DXR induced cardiomyopathy. Idebenone nanoparticles were prepared by antisolvent precipitation method. Male Wistar rats were divided into three groups. The first group that underwent no treatment was accepted as control group; the second group was treated with a single intraperitoneal injection of DXR (20 mg/kg); the third group was treated with oral idebenone nanoparticles (50 mg/kg) starting 18 days before DXR injection. The blood samples were collected to measure cardiac marker enzymes CKMB and LDH, serum creatinine and oxidative stress in mononuclear cells. The architectural damage was quantified by hematoxylin eosin stain. Average mean diameter observed for idebenone nanoparticles was 0.095 ± 0.012 m. The cardiac marker enzymes were found to be elevated as compared with vehicle treated control rat. DXR treatment showed significant decrease in the activity of endogenous antioxidant enzymes and alteration in haemapoietic and immunological indices. Treatment with idebenone nanoparticles markedly improved hemodynamic and left ventricular dysfunction and reduced the levels of biological serum markers. DXR treatment also decreased cell viability and increased apoptosis in the myocardium which were prevented by the treatment with NCLI. Moreover, NCLI treatment showed anti-inflammatory and antioxidant effects as evidenced by significant increase in the activity of SOD, GPx and GST. Treatment with nanoparticles of idebenone appears to block the development of DXR mediated cardiotoxicity.

In Vitro Antioxidant Activity of Idebenone Derivative-Loaded Solid Lipid Nanoparticles

“…As expected from calculated Log P values, IDE esters were less water soluble than IDE (water solubility: IDE 12.5 µg/mL; IDETRL 3.1 µg/mL; IDELIP 6.4 µg/mL). IDE water solubility determined in this work was in same order of magnitude of that reported in literature [ 32 ]. Plotting IDE and its esters water solubility vs. their Log P values, we observed a decrease of water solubility when increasing Log P values ( Figure 2 ).…”

Nanotechnology inspired tools for mitochondrial dysfunction related diseases

“…It is insoluble in water and shows limited bioavailability after oral administration. To obtain enhanced solubility and increased bioavailability of IDB, NPs were constructed using various stabilizers including hydrophilic polymers, amphiphilic polymers, and surfactants such as iabrasol, Brij 35, Pluronic F-68, Tween 80, sodium lauryl sulphate and hydroxypropyl methylcellulose (165). Doxorubicin induced cardiotoxicity characterized by decreased body weight and heart weight was supplemented by these NPs (50 mg/kg) resulting improved body and heart weight.…”