Cardioprotective Effect of Clarithromycin on Doxorubicin-Induced Cardiac Toxicity in Rats.

Abstract

Doxorubicin is an anthracycline group antibiotic and has long been used as an antineoplastic agent. The most important side effect that limits the usage of doxorubicin is cardiotoxicity, which is observed at cumulative doses. We investigated the protective effect of clarithromycin that is known to have antioxidant and anti-inflammatory effects against Doxorubicin related cardiotoxicity. The aim of our study was to evaluate the effects of clarithromycin in the antioxidant enzyme status and myocardium of doxorobucine-treated rats. A total of 28 adult, male Wistar rats (200-250 g) were divided into 4 groups. Group I was the control group, rats in group 2 were administered doxorubicin, rats in group 3 were administered clarithromycin, and rats in group 4 were administered Doxorubicin + Clarithromycin. Following the scarification of all rats, antioxidant (glutathione) and oxidant (malodialdehyde) levels were measured in the cardiac tissue. Additionally, the cardiac muscles were evaluated histopathologically via hematoxylin eosin staining. The antioxidant amount (glutathione) was significantly higher in the treatment group compared to the doxorubicin group (p= 0.025), whereas the amount of oxidant (malondialdehyde) was significantly lower (p= 0.022). The histopathological examination revealed significant cardiotoxicity in the Doxorubicin group and significant reduction in the cardiotoxicity in the Doxorubicin + Clarithromycin group. The results obtained in this study provide evidence for the usefulness of the clarithromycin as a cardioprotective agent. Grup 1 kontrol grubuydu, grup 2' de ki ratlara doksorubisin, grup 3' de ki ratlara klaritromisin ve grup 4' e doksorubisin+klaritromisin (tedavi grubu) uygulandı. Skarifikasyonu takiben tüm ratların kalp dokusunda antioksidan (glutatyon) ve oksidan (malodialdehid) düzeyleri ölçüldü.Buna ek olarak myokard dokusu hematoksilen-eozin ile boyanarak histopatolojik olarak değerlendirildi. Antioksidan (glutatyon) miktarı, tedavi grubunda doksorubisin grubuyla karşılaştırıldığında önemli derecede yüksekti (p= 0.025), oysa oksidan (malodialdehid) miktarı önemli derecede düşük saptandı (p= 0.022). Histopatolojik değerlendirmede doksorubisin grubunda ciddi kardiyotoksisite saptanırken doksorubisin + klaritromisin uygulanan grupta kardiyotoksisite de ciddi azalma belirlendi. Bu çalışmada elde edilen sonuç, klaritromisinin doxorubisine bağlı kardiyotoksitenin engellenmesinde kullanılabilecek kardiyoproduktif etkiye sahip bir ajan olduğudur.

Doxorubicin-Induced Cardiotoxicity in Adult Male Albino Rats and the Ameliorative Effects of Achillea Fragrantissima Crude Extract, Its Combined Ethyl Acetate/n. Butanol Fraction, and Vitamin E

“…However, its therapeutic efficacy is restricted by its hazardous toxic effects such as cardiotoxicity, which might jeopardize the patient's health (53,54). The results of current study regarding oxidative stress and apoptosis pathways were in accordance with similar studies that used the same studied dose of DOX (34,35,37,39). Moreover, our findings were also in line with previous studies of different models of DOX-induced cardiotoxicity (1,6,36,(60)(61)(62)(63).…”

“…HCl was added to the test solutions. The DOX dose used in our study was chosen based on its induction of cardiotoxicity in rats as implicated by previous studies (32)(33)(34)(35)(36)(37)(38)(39) Vitamin E dose utilized in this study was based on earlier research showing that this dose is efficient in lowering lipid peroxidation and raising levels of antioxidant enzymes in experimental animal models (40)(41)(42)(43).…”

Lycopene Attenuates Tulathromycin and Diclofenac Sodium-Induced Cardiotoxicity in Mice

“…For example, erythromycin, azithromycin, roxithromycin and clarithromycin can reduce erythrocyte MDA levels in guinea pigs with experimental otitis media [ 31 ]. Moreover, clarithromycin (at low doses) was shown to increase GSH levels in cardiac tissue after exposure to doxorubicin [ 32 ]. On the other hand, tilmicosin [ 15 ] and tulathromycin [ 9 ] were shown to increase the serum and cardiac tissue levels of MDA, respectively.…”

The nucleolus, an ally, and an enemy of cancer cells

“…Although it is an efficient anticancer agent with a broad spectrum of action from hematological cancers to solid tumors, its administration is restricted because of side effects. Cardiotoxicity is the major detriment upon application of Dox which significantly decreases antioxidant compounds in tissues (Dogan et al 2014 ). Oxygen-derived free radicals damage nuclear and mitochondrial DNA which induces apoptosis of cardiomyocytes, thus antioxidative strategy should be introduced for cardioprotection (Mobaraki et al 2017 ).…”