Protection against acute adriamycin-induced cardiotoxicity by nigella sativa oil, thymoquinone, garlic extract and COQ[10] in rats

ABSTRACT

Oxidative stress is a major etiologic factor in adriamycin [ADR]-induced cardiotoxicity that limits the clinical efficacy of this anticancer drug. Since, many beneficial health-related biological properties are attributed to Nigella sativa L. oil [NSO], thymoquinone [TQ], garlic, and Coenzyme Q-10, the present study examined the cardioprotective effect of these remedies against ADR-induced cardiotoxicity. The study was carried out on 110 male Albino rats. They were divided into a control group [10 rats] and 5 groups of ADR-treated rats [n=20 in each] as follows [i] ADR, [ii] CoQ10+ADR [iii] NSO+ADR [iv] Garlic+ADR and [v] TQ+ADR groups. Administration of CoQ10, NSO, garlic, and TQ were started one week prior to ADR and continued once daily thereafter for the next 2 weeks. The assessment of cardiac affection was carried out by measuring the level of serum creatine kinase [CK] and lactate dehydrogenase [LDH]. Also, activities of superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPX], cytosolic aconitase [c-aconitase] as well as the malondialdehyde [MDA] and cell iron content were measured in myocardial tissue homogenate. Moreover, light and electron microscopic changes were scored. The administration of ADR to the experimental rats produced wide range of changes. A significant decrease in activities of the antioxidant enzymes SOD, CAT and GPX in ADR-treated rats was found compared to normal control values. Also, myocardial MDA level was significantly high as well as serum LDH and CK denoting myocardial injury. The ADR-treated rats also showed significant inhibition of myocardial c-aconitase activity and rise of cell iron content compared to control myocardium. The histological results of this group revealed hypereosinophilia, myofibrillar damage, nuclear abnormalities, mitochondrial degeneration and diminished glycogen. Neither CoQ10 nor the whole oil of nigella sativa significantly modified ADR-induced impairment in SOD, GPX or CAT activity. CK was significantly less elevated in the NSO but insignificantly different in the CoQ10 while LDH was significantly less elevated in both groups compared to ADR group. Activity of c-aconitase was significantly higher in NSO than CoQ10 and ADR groups while cellular iron was insignificantly different. Also, survival was significantly improved in the NSO but not in the CoQ10 compared to ADR group. These findings were further documented by the histological findings. Examination of ADR-CoQ[10] treated rats showed extensive cellular damage including the mitochondria, intercalated discs, the cytoskeleton, the nuclei and diminished glycogen deposition. Conversely, 3 weeks administration of TQ and garlic in the present study have yielded encouraging results against acute ADR-induced cardiotoxicity in rats, as indicated by 100% survival rate which was found in these groups versus 40-50% in the ADR and CoQ10 treated groups. Moreover, they have been associated with conserved activity of myocardial antioxidant enzymes GPX, SOD and CAT with suppression of MDA formation and less accumulation of cellular iron compared to ADR, CoQ10 and NSO treated groups. The histological results further proved this results and revealed high degree of myocardial protection in TQ-treated rats and garlic-treated rats respectively where the most examined myocytes were nearly normal. Thymoquinone [TQ] and garlic had shown significant cardioprotective effect much superior to NSO and CoQ10 against ADR-induced myocardial toxicity. The low TQ content in the chosen dose of NSO could be the underlying cause of lacking therapeutic effect although a strong antioxidant effect have been recently reported with this dose of NSO. Hence, a larger dose of NSO and probably of CoQ10 can be subjected to further study for protection against ADR-induced cardiac injury