Dapsone Ameliorates Isoproterenol-Induced Myocardial Infarction via Nrf2/ HO-1; TLR4/ TNF-α Signaling Pathways and the Suppression of Oxidative Stress, Inflammation, and Apoptosis in Rats

Abstract

Myocardial infarction (MI) is a critical condition that can happen with high doses or rapid termination of beta blockers therapy. The study aimed to evaluate the potential anti-toxic value of DAP against isoproterenol (ISO) - induced MI. Twenty-eight male Wistar rats were used for the study. The rodents were assigned to four groups (n = 7) and the treatments were given for 12 days as follows; Group 1 (control): were administrated normal saline, Group 2 (DAP control): were administrated DAP (10 mg/kg/day IP), Group 3 (ISO group): were administrated ISO (100 mg/kg, IP on the 11th and 12th days of the experiment), and Group 4 (DAP + ISO): co-treated with DAP plus ISO. The measured parameters were cardiac malondialdehyde (MDA), reduced glutathione (GSH), total nitrite/nitrate (NOx), catalase (CAT), serum cardiac biomarkers; CK-MB, ALT, LDH, and ALK-PH. Also, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), toll-like receptor 4 (TLR4), caspase-3 activity, and hepatic BAX and Bcl-2 were also assessed. Also, histological examination and vimentin immuno-expressions were studied. ISO group exhibited MI as evidenced by the elevation in serum cardiac biomarkers, MDA, NOx, IL-1β, TNF-α, and caspase-3 together with the reduction in GSH, Nrf2, HO-1 levels, and a faint vimentin immuno-reaction. Histological alterations revealing distorted cardiomyocytes; vacuolation, edema, pyknosis, and fragmentation were also noticed. DAP significantly ameliorated all the examined toxicity indicators. DAP revealed efficient ameliorative actions against ISO-caused MI by marked reduction in myocardial infarct size and suppressed oxidative stress, inflammation, and apoptosis via the up-regulation of the Nrf2/HO-1; TLR4/TNF-α signaling pathways.

Ginsenoside Rc attenuates myocardial ischaemic injury through antioxidative and anti-inflammatory effects

“…The pathological inflammatory process leads to the generation of ROS that damage macromolecules in cardiomyocytes (Abdelzaher et al. 2021 ). Accumulating evidence demonstrate that the Nrf2/HO-1 signalling plays a pivotal role in regulating inflammation (Khalil et al.…”

Peroxiredoxin-5 Knockdown Accelerates Pressure Overload-Induced Cardiac Hypertrophy in Mice

“…Apoptosis is known to contribute to various cardiovascular diseases, including heart failure, myocardial infarct, and reperfusion injury [ 35 , 36 ]. Previous research has also shown that cardiac hypertrophy is related to a reduced cell number due to enhanced apoptosis [ 37 , 38 ].…”

Catecholamine Surges Cause Cardiomyocyte Necroptosis via a RIPK1–RIPK3-Dependent Pathway in Mice

“…Myocardial TNFα and IL1β protein levels were markedly increased in rats treated with two consecutive daily doses of ISO (100 mg/kg/day, i.p.) ( 37 ). Hence, it is very likely that autocrinal or paracrinal TNFα and its activation of TNFR1 mediate the activation of the RIPK1–RIPK3–MLKL pathway by the ISO treatment ( Figure 6 ), although no PubMed searchable studies have tested the requirement of TNFR1 in the induction of cardiomyocyte necrosis by catecholamine surges yet.…”

“…Calcium overload and myofibril over-contraction, which can be a direct result of excessive β-adrenergic stimulation from catecholamines and a secondary consequence of I/R injury, may contribute to cardiac dysfunction and injury ( 36 ). Additionally, β-adrenergic stimulation appears to be able to trigger inflammatory responses by upregulating the expression and release of inflammatory cytokines ( 37 ); and many compounds with an anti-inflammatory property can protect against cardiac injury induced by catecholamine surges ( 21 ), suggesting that the secondary injury from inflammation may also play a role in the cardiac injury by catecholamine surges. Necrotic cardiomyocyte death is the most prominent pathological feature of cardiac injury induced by catecholamine surges ( 19 ).…”