Toxicity of Atenolol and Propranolol on Rat Heart Mitochondria

Abstract

Propranolol and atenolol are known as β receptor blocker drugs. These drugs are used to treat some heart diseases. There are controversies in the relationship between the use of beta-blocker drugs and the level of reactive oxygen species (ROS). Mitochondria as one of the most important sources of ROS are considered as one of the targets of drug-induced cardiotoxicity. The aim of this study was to evaluate the effects of propranolol and atenolol on mitochondria isolated from the heart. To achieve this aim, several markers of mitochondrial and cellular toxicity were evaluated. The key results of this study are the increased ROS level, collapse in mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release as well as disruption of respiratory chain complex II in mitochondria in isolated heart mitochondria after exposure to propranolol and atenolol. The results indicate an increase in caspase-3 activity and a decrease in the ATP level in cardiomyocytes after exposure to propranolol and atenolol. The underlying mechanisms of propranolol and atenolol induced cardiotoxicity may be associated with alterations in mitochondrial function, oxidative stress, and changes in the mitochondrial membrane.

Does Systemic Arterial Hypertension Change the Function of the Stomatognathic System?

“…These drugs can act at neuromuscular transmission, at both pre-and postsynaptic levels and may produce neuromuscular dysfunction. The calcium channel blockers, as verapamil and amlodipine, can impair neuromuscular transmission in individuals without neuromuscular disease, which may cause misinterpretation of single fiber electromyography studies carried out to investigate neuromuscular junction disorders (Ozkul, 2007;Seydi et al, 2020). In our study, 17% and 53% of hypertensive individuals make use calcium channel blockers and diuretics, respectively.…”

Cyclosporin-A reduced the cytotoxicity of propranolol in HUVECs via p38 MAPK signaling

“…Although some studies have shown antioxidant properties for Cyclosporine A and PROP independently, [ 22 , 23 ] some other studies have demonstrated their toxic effects. [ 24 ] Recent research has suggested that ROS can trigger PROP-induced cell death; therefore, ROS inhibition is responsible for reducing PROP-induced cell apoptosis.…”

Assessing Drug-Induced Mitochondrial Toxicity in Cardiomyocytes: Implications for Preclinical Cardiac Safety Evaluation

“…Inhibition can be caused by directly inhibiting the activity of MRC complexes. For example, zoniporide [ 64 ], naproxen [ 60 , 138 ], dronedarone [ 139 ], and mubritinib [ 140 ] inhibit complex I; propranolol and atenolol disrupt complex II [ 119 ]; celecoxib suppresses complex IV [ 14 ]; and As 2 O 3 inhibits complex I, III, and IV [ 141 ]. OXPHOS may also be blocked by inhibition of the expression of MRC complexes, such as by mitoxantrone [ 100 ].…”

“…Drugs inducing cardiotoxicity by targeting mitochondria invariably proceed to MMP collapse and mPTP opening ( Table 3 ). Antineoplastic agents, including DOX [ 73 , 81 , 164 ], As 2 O 3 [ 84 , 229 ], and imatinib [ 91 ]; β adrenergic receptor blockers, such as propranolol and atenolol [ 119 ]; antiarrhythmic drugs dronedarone and amiodarone [ 139 ]; antibiotics erythromycin and clarithromycin; NSAIDs such as naproxen, diclofenac, and celecoxib [ 60 ]; and diabetes drug pioglitazone [ 122 ] have all been reported to cause these harmful effects. mPTP opening and MMP decrease consequently induce loss of respiratory control and imbalance in ATP production, and loss of mitochondrial components such as ATP, NAD+, and glutathione, leading to water accumulation in the matrix, which causes mitochondrial osmotic swelling, IMM unfolding, and the rupture of the OMM [ 230 , 231 ].…”