Cerebral ischemia-reperfusion induced cardiac injury in rats: involvement of oxidative stress, apoptosis, TLR4, NF-κB and HSP70: the rescue effect of losartan.

This study aimed to explore the effect of cerebral ischemia reperfusion and losartan on oxidative stress, inflammation, apoptosis and its molecular mediators in the rat heart. The groups were as follows (n = 6): 1) sham 2) ischemia-reperfusion (IR, 20 min ischemia, 24 hours reperfusion), 3) ischemia-reperfusion + losartan (IR + LOS, 3 mg/kg, ip, 1 hour before ischemia). In IR animals' heart Malondialdehyde (MDA) and Total oxidative status (TOS) increased while Total antioxidant capacity (TAC) and Superoxide dismutase (SOD) concentration decreased compared to the sham rats. Cerebral IR increased apoptotic index evidenced by increased cytochrome c and c-caspase3/p-caspase3 ratio, as well as elevated Toll-like receptor4 (TLR4), Nuclear factor kappa B (NF-κB) and Heat Shock Protein70 (HSP70) in the heart tissue. These alterations could be mitigated by losartan. TLR4 is positively correlated with NF-κB, r = 0.61; MDA, r = 0.64; TOS, r = 0.59 (p <0.01), cytochrome c, r = 0.83; c-caspase3/p-caspase3, r = 0.72 (p <0.001) and negatively correlated with SOD, r = -0.73 and TAC, r = -0.83 (p <0.001). In all, cerebral IR increased cardiac oxidative stress and apoptosis which positively correlates with TLR4/NF-κB pathway. Additionally, losartan can be considered as a potential target for preventing cardiac injury following stroke.Clinical significance: N/A.