Increased serum levels of triglycerides cholesterol

Increased serum levels of triglycerides, cholesterol, high density lipoproteins and very low density lipoprotein were observed in Dox alone group which indicated that doxorubicin may interfere with metabolism or biosynthesis of lipid. Similar observations were also reported by [9,31]. Pretreatment of rats with FLC alone, ω-3-FA alone and concomitant administration of FLC and ω-3-FA significantly prevented the myocardial alterations and normalized the serum lipid profile. The protective effect exerted by FLC and ω-3-FA can be attributed to the combination of antioxidant and lipid lowering actions of these agents independently. The antiatherosclerotic [2] and antioxidant [3,4] activities of FLC containing SDG have been reported. Holub [32] reported cholesterol and triglyceride lowering effect of ω-3-FA containing algal DHA. Although the mechanism for Dox-induced apoptosis is unclear. It is observed that Dox strongly increased reactive oxygen species (ROS), a known trigger of apoptosis [33]. We observed Dox-treated heart samples higher degree of DNA degradation which is an indication of oxidative stress and fragmentation of chromosome possibly leading to apoptosis. However, Dox+FLC, Dox+ω-3-FA treated hearts had reduced amount of DNA degradation, whereas concomitant administration of FLC and ω-3-FA+Dox-treated heart samples showed less degree of DNA degradation. Administration of Dox produced severe changes in myocardium with respect to myocardial atrophy, nuclear pyknosis, cytoplasmic eosinophilia and inflammation which confirms cardiotoxicity in rats. These changes are previously reported by other researchers [34]. Pretreatment of rats with FLC alone and ω-3-FA alone exhibited comparatively less degree of damage compared to Dox alone group whereas in case of concomitant administration of FLC and ω-3-FA showed partial protection. Further transmission IWR-1-endo Supplier microscopic studies provided credence to the cardioprotective effect. Restoration of vacuolization and reduction of intracellular damage in case of concomitant administration of FLC and ω-3-FA indicated protection in terms of integrity of the subcellular structure in doxorubicin-treated rat hearts. Micallef and Garg [35], showed cardioprotective benefits of combined ω-3-PUFA and plant sterol supplementation in hyperlipidemic individuals, wherein ω-3-PUFA and plant sterols as lipid-lowering agents provided greater risk reduction compared to either of the supplements alone. They used non-pharmacological approach which showed lipid-lowering benefits, down regulation of markers of systemic inflammation and reduction in overall cardiovascular risk. In present study, pharmacological approach was used by oral administration of test substances (ω-3-FA and FLC).
Conclusion In conclusion, the present findings demonstrated that, concomitant administration of FLC (500mg/kg) and ω-3-FA (1mL/kg) lowered TNF-α level, normalized ST, QT and MABP, elevation in GSH and MDA, SOD lowered and normalized lipid profile. The treatment provided protection from DNA degradation at cellular level. Histopathology of heart tissue (both light and electron microscopical) confirmed the cardioprotective effect. The concomitant treatment reduced the mortality due to Dox administration. Thus antioxidant, antihyperlipidemic, anti-inflammatory and anti-apoptotic actions seem to be the probable mechanisms in doxorubicin induced cardiotoxicity. Hence, it can be concluded that FLC and ω-3-FA both have distinct mechanism for cardioprotection and the additive effect was observed in the present study due to concomitant administration of FLC and ω-3-FA. These data suggest a possible usefulness combination of FLC and ω-3-FA as a cardioprotective agent. The study reveals the role of flax lignan concentrate and ω-3-FA in preventing doxorubicin-induced cardiotoxicity. Additional clinical trials using this combination to further extrapolate these experimental results are necessary, also more molecular studies to reveal the underlying mechanisms in this direction is warranted.