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Protective effects of montelukast against doxorubicin-induced cardiotoxicity in rats
Olcay Murat Disli1, Mehmet Cengiz Colak1, Mehmet Ediz Sarihan2
1Inonu University, Faculty of Medicine, Department of Cardiovascular Surgery, Malatya, TÜRKİYE.
Background:
We investigated possible protective effect of montelukast (MTL) on doxorubicin (DOX)-induced cardiac damage in a rat model.
Methods:
Thirty-five rats were randomised into 5 equal groups including 7 rats in each group: Control (C) group; MTL group (10 mg/kg MTL via the orogastric route for 10 days); DOX group (single dose of 20 mg/kg) DOX intraperitoneally (i.p); DOX+MTL group (3 days after the single dose of 20 mg/kg DOX i.p., 10 mg/kg MTL continued for 10 days via the orogastric route); and MTL+DOX group (10 mg/kg MTL continued for 10 days via the orogastric route, single dose 20 mg/kg DOX administrated after last dose MTL).
Results:
In the MTL + DOX group, a significant decrease in mean arterial blood pressure (MBP) and a marked reduction in oxygen saturation were observed together. On ECG, QT interval indicated a significant increase in DOX group compared to MTL group and a significant increase in MTL+DOX group, compared to C and MTL groups. DOX treatment led to significant increase in MDA levels, decrease in SOD levels, and increase in MPO activities in the heart and aorta tissue. Myocyte degeneration seen in DOX group significantly reduced in the MTL+DOX and DOX+MTL groups histopathologicaly.
Conclusion:
Our results indicate that MTL has protective effects against DOX-induced cardiotoxicity in rats.
Insights
Montelukast (MTL) shows protective effects against doxorubicin (DOX)-induced heart damage in rats. This study demonstrates MTL
Area of Science:
- Cardiology
- Pharmacology
- Toxicology
Background:
- Doxorubicin (DOX) is a widely used chemotherapy agent.
- DOX can cause significant cardiotoxicity, limiting its clinical use.
- Investigating protective agents against DOX cardiotoxicity is crucial.
Purpose of the Study:
- To evaluate the potential cardioprotective effects of montelukast (MTL) against DOX-induced cardiac damage.
- To assess MTL's impact on physiological and biochemical markers of cardiotoxicity in a rat model.
Main Methods:
- A rat model was used with five groups: Control, MTL only, DOX only, DOX followed by MTL, and MTL followed by DOX.
- DOX was administered intraperitoneally, while MTL was given via oral gavage.
- Cardiac function, ECG, oxidative stress markers (MDA, SOD), MPO activity, and histopathology were analyzed.
Main Results:
- DOX treatment significantly increased QT interval, MDA levels, and MPO activity, while decreasing SOD levels.
- DOX administration led to myocyte degeneration.
- MTL treatment, particularly in the MTL+DOX and DOX+MTL groups, significantly reduced these adverse effects and showed improved histopathological findings.
Conclusions:
- Montelukast (MTL) exhibits significant protective effects against doxorubicin (DOX)-induced cardiotoxicity in rats.
- MTL may mitigate DOX-induced cardiac damage by reducing oxidative stress and improving cardiac tissue integrity.
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