Vitamin E and telmisartan attenuates doxorubicin induced cardiac injury in rat through down regulation of inflammatory response

Abstract

BackgroundThe importance of doxorubicin (Dox), as a potent antitumor antibiotic, is limited by the development of life-threatening cardiomyopathy. It has been shown that free radicals are involved in acute doxorubicin-induced toxicity. The aim of this study was to determine the protective effect of vitamin E and telmisartan in acute doxorubicin induced cardiotoxicity.MethodsThirty two male Sprague - Dawly rats were involved in this study and were randomly separated into 4 groups, eight rats in each group, one group received normal saline I.P as control and second group received doxorubicin 20 mg/kg I.P, the other two groups also received doxorubicin 20 mg/kg I.P as single dose after seven cumulative doses (for seven days) of vitamin E (100 mg/kg) and telmisartan (1 mg/kg) respectively. Immunofluorescent staining for monocytes infiltration and analyses of plasma by (ELISAs) for MCP-1and troponin I. Western immunoblotting assay for ICAM-1, while left ventricular function was analyzed by microcatheter, also estimated the level of oxidative stress parameters (MDA and Catalase) and cardiac enzymes activities (CK-MB and LDH) before starting drugs treatment and after treatment period by 48 hours.ResultsThe immunofluorescent staining showed that administration of vitamin E and telmisartan are attenuated of mononuclear cell infiltration; (p < 0.05 vs. Dox group), also reduced the level of chemokines MCP-1 and ICAM-1 expression compared with Dox group only, and there is marked reduction of myocardial troponin-I levels with improved LV function in vitamin E and telmisartan treated group. Doxorubicin treatment increased MDA, LDH, CK-MB levels significantly (P < 0.01), and were counteracted by administration of vitamin E and telmisartan, but did not significantly affect serum catalase activity.ConclusionsAntioxidant effect (Vitamin E and telmisartan) have been shown to decrease doxorubicininduced cardiotoxicity.

Comparative Study of the Protective Effect of Metformin and Sitagliptin against Doxorubicin-Induced Cardiotoxicity in Rats

“…Elevation of cardiac enzymes in rats following cumulative dose of doxorubicin was detected by Ref. 's [27,28]. Metformin through its activation of 5′-Adenosine Monophosphateactivated Protein Kinase (AMPK) reduces the generation of ROS [40] and increases endothelial nitric oxide synthase phosphorylation which prevents the opening of the mitochondrial permeability pores [41].…”

Thymol and Carvacrol Prevent Doxorubicin‐Induced Cardiotoxicity by Abrogation of Oxidative Stress, Inflammation, and Apoptosis in Rats

“…Significant elevations in serum levels of LDH, AST, CPK, CK‐MB, and cTn‐I in this study were attributed to DOX‐induced cardiac damage. The increase in serum TNF‐α indicates that DOX induces a cascade of inflammatory reactions with increased production of proinflammatory cytokines, particularly TNF‐α . Moreover, the increase in the caspase‐3 content (a key mediator of apoptosis in mammalian cells) contributes to DOX‐induced apoptosis .…”

Role of NF‐κβ and Oxidative Pathways in Atherosclerosis: Cross‐Talk Between Dyslipidemia and Candesartan

“…Aortic tissue was homogenized and treated with PBS containing 0.5% Triton X‐100 and a protease inhibitor cocktail, as described previously . Briefly, after protein quantification, equal amounts of protein were incubated with the relevant antibodies and protein A–sepharose beads at 4°C overnight and resolved in 8%–12% SDS‐PAGE depending on the molecular weight of the protein to be detected.…”