CARDIOPROTECTION BY A CANNABIS SATIVA SP EXTRACT AGAINST ISCHEMIA-REPERFUSION INJURY: INVOLVED MECHANISMS

GONZÁLEZ ARBELÁEZ LF; FANTINELLI JC; ANDRINOLO D; ARANDA MOSQUERA JO; COLMAN LERNER E; MOSCA SM

Mar del Plata, Buenos Aires

Congreso; SAIC.SAI.SAFIS 2018; 2018

The aim was to determine the effects of acute treatment of a cannabinoid extract (CBE), obtained from Cannabis Sativa sp against ischemia-reperfusion injury. The extract was characterized and quantified by gas chromatography coupled to mass spectrometry (GC-MS). The profile was: Δ9-tetrahydrocannabinol (Δ9-THC) : 1,35mg/ml; cannabidiol (CBD): 0,51mg/ml and cannabinol (CBN): 0,34mg/ml. Isolated rat hearts perfused by Langendorff system were assigned to the following experimental groups: Non-ischemic control (NIC): 110 min of perfusion; Ischemic control (IC): 30 min of global ischemia (GI) and 60 min of reperfusion (R) and CBE: 0,1ug/ml of the extract was administered during the first 10 min of R. Infarct size (IS) was determined by TTC staining. Systolic and diastolic function was assessed by left ventricular developed pressure (LVDP) and the left ventricular end diastolic pressure (LVEDP), respectively. To assess the oxidative stress, the glutathione reduced (GSH) content and the concentration of thiobarbituric acid reactive substances (TBARS) were measured. The expression of phosphorylated forms of eNOS, PKCε and Akt were also determined by western blot. CBE significantly decreased IS (2.3 ± 0.5 % vs. 31 ± 2 % in IC) and improved the post-ischemic recovery of myocardial function (LVDP: 64 ± 9 % vs. 17 ± 3 %; LVEDP: 15 ± 7 vs. 35 ± 9 mmHg) compared to IC group. The GSH content significantly increased (0.86 ± 0.10 vs. 0.78 ± 0.11 g/mg protein) and TBARS decreased (0.55 ± 0.05 vs. 1.10 ± 0.45 nmol/mg protein) in CBE treated hearts. The expression of P-eNOS, P-PKCε and P-Akt decreased approximately 60 % in IC and increased approximately 150 % in CBE, both compared to NIC. These data demonstrate that CBE reduced the cell death and myocardial contractile post-ischemic dysfunction and attenuated the oxidative damage produced by ischemia-reperfusion. These beneficial actions appear mediated by Akt/PKC/eNOS-dependent pathways.