Can Alpha-Pinene Prevent Methotrexate-Induced Cardiac and Hepatic Damage?

The effects of alpha-pinene (AP), a monoterpenoid, known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, on methotrexate (MTX)-induced cardiac and hepatic damage were investigated in this study. Male Sprague-Dawley rats were divided into Control, Vehicle, AP, MTX, and AP+MTX g...

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Bibliographic Details
Published in:	Physiological research Vol. 73; no. 4; pp. 621 - 631
Main Authors:	Cirrik, S, Hacioglu, G, Kabartan, E, Tezcan Yavuz, B, Sirin Tomruk, C
Format:	Journal Article
Language:	English
Published:	Czech Republic Institute of Physiology of the Czech Academy of Sciences 31-08-2024
Subjects:	Animals Antioxidants - pharmacology Bicyclic Monoterpenes - pharmacology Chemical and Drug Induced Liver Injury - metabolism Chemical and Drug Induced Liver Injury - pathology Chemical and Drug Induced Liver Injury - prevention & control Liver - drug effects Liver - metabolism Liver - pathology Male Methotrexate - toxicity Monoterpenes - pharmacology Monoterpenes - therapeutic use Myocardium - metabolism Myocardium - pathology Oxidative Stress - drug effects Rats Rats, Sprague-Dawley
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Summary:	The effects of alpha-pinene (AP), a monoterpenoid, known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, on methotrexate (MTX)-induced cardiac and hepatic damage were investigated in this study. Male Sprague-Dawley rats were divided into Control, Vehicle, AP, MTX, and AP+MTX groups (n=7). AP (50 mg/kg/day, 14 days) was applied subcutaneously in the AP and AP+MTX groups. MTX (20 mg/kg) was injected three days before sacrification. Serum CK-MB, troponin T, ALT, and AST levels, as well as cardiac and hepatic MDA, GSH, caspase-3, and p53 levels, were measured by ELISA. Histological changes in tissues were evaluated by scoring in terms of tissue damage and cellular degeneration parameters after hematoxylin-eosin staining. MTX caused significant increase in serum CK-MB, troponin T, ALT, and AST levels, hepatic and cardiac lipid peroxidation, GSH depletion, and caspase-3 level. However, tissue levels of p53 did not change significantly. MTX-induced histological deterioration was observed in both tissues. These MTX-induced changes were significantly reduced in the AP+MTX group. Present results show that MTX-induced cardiac and hepatic damage is prevented by AP pretreatment. This protection can be attributed to the antioxidant and anti-apoptotic properties of AP. Considering the importance of MTX in cancer treatment, AP appears to have highly promising potential as a cardioprotective and hepatoprotective agent in anti-tumoral therapy. Key words: MDA, GSH, Caspase-3, p53, Oxidative stress, Apoptosis.
ISSN:	0862-8408 1802-9973
DOI:	10.33549/physiolres.935338