Dual Role of Cannabidiol in Mitigating Apoptosis and Inflammation in Cardiovascular Complications of Lung Ischemia-Reperfusion

Objective: Lung ischemia-reperfusion (I/R) injury is a critical complication in thoracic surgeries and lung transplantation, leading to oxidative stress, inflammation, and apoptosis. Secondary cardiac damage often occurs due to the systemic inflammatory response, highlighting the need for protective interventions. Cannabidiol (CBD), known for its anti-inflammatory, antioxidant, and anti-apoptotic properties, may mitigate this damage through modulation of apoptotic (B-cell lymphoma 2 [Bcl-2], Bcl2-associated X protein [Bax] and inflammatory (interleukin 10 [IL-10]) markers. Material and Method: This study involved forty male Wistar albino rats divided into four groups: Control, Lung I/R induced cardiac injury (LICI), LICI treated with CBD (LICI+CBD), and CBD-only. Lung I/R was induced by clamping the left lung hilus for 60 minutes, followed by 60 minutes of reperfusion. The cardiac and aortic tissues were collected post-intervention, and histopathological as well as immunohistochemical analyses were conducted to assess the expression levels of Bax, Bcl-2, and IL-10. Results: Histopathological findings revealed significant tissue damage in the LICI group, including increased hyperemia, hemorrhage, mononuclear cell infiltration, and necrosis compared to the control. CBD treatment markedly reduced these pathological markers. Immunohistochemical analysis showed a significant increase in pro-apoptotic Bax and a decrease in anti-apoptotic Bcl-2 and IL-10 in the LICI group. Conversely, the LICI+CBD group demonstrated reduced Bax levels and elevated Bcl-2 and IL-10 expression, indicating CBD's role in reducing apoptosis and inflammation. Conclusion: CBD exhibits cardioprotective effects in lung I/R-induced cardiac injury by decreasing Bax-driven apoptosis, maintaining Bcl-2 levels, and upregulating IL-10 expression. These findings suggest CBD as a promising therapeutic agent for reducing secondary cardiac injury in lung I/R scenarios, though further studies are warranted to confirm its efficacy in clinical settings.