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Al Katheeri, Sheikh, Nalin, and Ojha: β-Caryophyllene, a cannabinoid receptor type-2 agonist protects against doxorubicin-induced cardiotoxicity

Introduction: Doxorubicin (Dox) is one of the most widely used and highly active antitumour drugs, but its cumulative cardiotoxicity has been a major concern in cancer therapeutic practice. The cardiotoxic side-effects of Dox are associated with increased oxidative/nitrosative stress, inflammation and apoptosis. β-Caryophyllene (BCP) is a natural bicyclic sesquiterpene commonly found in the essential oils of many vegetables, fruits and spices. It has been approved by the US Food and Drug Administration as a food additive and flavouring agent, and termed as a dietary phytocannabinoid. It has recently been shown that BCP has a number of beneficial effects in different biological systems, which include antioxidant, antineoplastic, antidepressant, anti-inflammatory, cardioprotective and anxiolytic effects.

Objectives: BCPs recent identification as a CB2 receptor agonist generated interest to investigate whether it can counter the Dox-induced cardiotoxicity in rats.

Materials and methods: BCP (50 mg/kg/day) dissolved in corn oil was administered orally to male Wistar rats for 21 days while the Dox control group received 12.5 mg/kg/ml intraperitoneally and the vehicle, corn oil, was administered daily and naive rats were used as controls. After 72 hours of Dox administration, the animals were sacrificed and hearts were collected.

Results: BCP was found to protect against Dox-induced reduction in enzyme activities of superoxide dismutase, catalase and depletion of reduced glutathione and accumulation of malondialdehyde and nitric oxide. BCP pretreatment also significantly reduced the inflammatory markers Il-β1, IL-6 and TNF-α and restored the levels of Dox-induced rise of serum glutamic-pyruvic transaminase, serum glutamic oxaloacetic transaminase, serum lactate dehydrogenase and creatine kinase levels. Furthermore, the histopathological changes strengthened the protective effects of BCP against Dox-induced cardiotoxicity.

Conclusions: BCP may be a suitable cardioprotective agent to reduce the cardiotoxic effects of Dox by reducing oxidative/nitrosative stress and inflammation. Given the widespread occurrence, safety and efficacy profile, BCP may offer excellent therapeutic/preventative qualities as it appears to be a safe functional non-psychoactive and macrocyclic anti-inflammatory CB2 receptor ligand in foodstuffs.

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