The Impact of Pharmacotherapy for Heart Failure on Oxidative Stress—Role of New Drugs, Flozins

Abstract

Heart failure (HF) is a multifactorial clinical syndrome involving many complex processes. The causes may be related to abnormal heart structure and/or function. Changes in the renin-angiotensin-aldosterone system, the sympathetic nervous system, and the natriuretic peptide system are important in the pathophysiology of HF. Dysregulation or overexpression of these processes leads to changes in cardiac preload and afterload, changes in the vascular system, peripheral vascular dysfunction and remodeling, and endothelial dysfunction. One of the important factors responsible for the development of heart failure at the cellular level is oxidative stress. This condition leads to deleterious cellular effects as increased levels of free radicals gradually disrupt the state of equilibrium, and, as a consequence, the internal antioxidant defense system is damaged. This review focuses on pharmacotherapy for chronic heart failure with regard to oxidation–reduction metabolism, with special attention paid to the latest group of drugs, SGLT2 inhibitors—an integral part of HF treatment. These drugs have been shown to have beneficial effects by protecting the antioxidant system at the cellular level.

The Role of Oxidative Stress and Inflammatory Parameters in Heart Failure

“…Nox-4, primarily localized to mitochondria in cardiac myocytes, plays a crucial role in increasing ROS production and subsequent cardiac remodeling due to factors such as pressure overload and aging. NADPH oxidase activity amplifies significantly in response to various triggers linked to the pathophysiology of HF, including mechanical stretch, angiotensin II, ET-1 and TNF-α [18,[22][23][24][25][26][27][28].…”

“…Nitric oxide synthases (NOSs), essential for nitric oxide (NO) synthesis, are involved in HF, potentially producing harmful O −2 instead of NO, increasing ROS generation. RNS, derived from nitric oxide and superoxide through enzymatic activity, play a role in oxidative stress and can lead to the formation of free radicals [7,22,28]. Under pathological conditions, NOS can become uncoupled, resulting in the generation of superoxide (O 2− ) as a byproduct of nitric oxide synthesis, often associated with electron leakage during mitochondrial respiration [7].…”

“…The right ventricle (RV) exhibits heightened vulnerability to oxidative stress in comparison to the left ventricle (LV). This increased susceptibility in the RV is partly attributed to its inability to regulate the expression of manganese superoxide dismutase, which contributes to oxidative stress in the RV [7,27,28]. Oxidative stress plays a pivotal role in pulmonary vascular remodeling, with monocytes accumulating in pulmonary arterioles, leading to ROS generation.…”

New Insights into the Nephroprotective Potential of Lercanidipine

“…SGLT-2 inhibitors selectively inhibit sodium-glucose cotransporter 2, thereby blocking the reabsorption of filtered glucose, resulting in glycosuria [ 156 ]. These are drugs with cardio- and nephroprotective effects, which also prevent hyperkalemia and have a weak hypotensive effect [ 157 , 158 ]. They are extremely useful in patients with type 2 diabetes with additional cardiovascular or nephrological burden [ 157 , 159 ].…”

“…These are drugs with cardio- and nephroprotective effects, which also prevent hyperkalemia and have a weak hypotensive effect [ 157 , 158 ]. They are extremely useful in patients with type 2 diabetes with additional cardiovascular or nephrological burden [ 157 , 159 ].…”