Therapeutic Targeting of Oxidative and Apoptotic Pathways to Maintain Redox Homeostasis in Diverse Disease and Cellular Models | Book Publisher International

 

Introduction: Oxidative stress results from an imbalance between the generation of reactive oxygen species (ROS) and the body's antioxidant defences. This imbalance contributes significantly to the pathogenesis of a wide array of disorders, including neurodegenerative, cardiovascular, metabolic, and reproductive conditions, as well as adverse outcomes related to cryopreservation. A critical downstream consequence of ROS accumulation is lipid peroxidation (LPO), which leads to the formation of cytotoxic aldehydes like malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). These aldehydes form adducts with cellular macromolecules, disrupting homeostasis and cellular function.

 

Central Themes: This work emphasises the critical interplay between oxidative stress, lipid peroxidation, and apoptosis in the progression of disease and cellular dysfunction. It explores how ROS trigger biochemical cascades that compromise redox balance, damage cellular macromolecules, and activate programmed cell death. It further highlights the molecular mechanisms linking oxidative injury to apoptosis, emphasising the roles of caspases, Bcl-2 family proteins, and mitochondrial signalling. These interconnected pathways form the foundation for therapeutic targeting, as oxidative stress and cell death represent converging points in a wide spectrum of pathological and cryopreservation-related conditions.

 

Key Therapeutic Approaches: A comprehensive categorisation of pharmacological strategies aimed at mitigating oxidative stress and modulating apoptosis is presented, highlighting their therapeutic relevance across various pathophysiological conditions. Among the most widely studied interventions are LPO inhibitors and aldehyde scavengers such as aminoguanidine and pyridoxamine, which neutralise reactive carbonyl species like MDA and 4-HNE. Metal chelators, particularly those targeting iron, play a pivotal role in regulating ferroptosis and limiting redox-active metal-catalysed ROS generation. Enhancing endogenous antioxidant capacity through glutathione (GSH) mimetics, prodrugs, and enhancers represents another critical approach to restore redox balance. Enzymatic ROS sources are targeted using inhibitors of xanthine oxidase and nitric oxide synthases, both of which contribute significantly to oxidative burden in pathological states. Mitochondrial-targeted antioxidants, such as MitoQ and tiron, have shown improved specificity and efficacy by directly protecting mitochondrial integrity, a major site of ROS generation and apoptosis signalling. Additionally, NADPH oxidase inhibitors help to reduce one of the primary sources of cellular ROS in inflammatory and cardiovascular diseases. Apoptosis inhibitors that modulate key regulators, including caspases and Bcl-2 family proteins, offer further protection by preventing programmed cell death in oxidative stress-affected cells. Finally, antioxidant enzyme mimetics such as those replicating the activity of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) represent a promising class of therapeutics designed to restore or enhance the body’s natural enzymatic defence systems. Collectively, these diverse yet interconnected approaches provide a multifaceted strategy for addressing oxidative stress and apoptosis across a broad range of clinical and experimental settings.

 

Conclusion: This extensive resource systematically organises and presents targeted compounds and modulators of oxidative and apoptotic signalling pathways, emphasising their therapeutic relevance across a spectrum of oxidative stress-related diseases and reproductive dysfunctions, including the oxidative challenges inherent to cryopreservation. By providing a detailed and structured analysis of pharmacological interventions ranging from antioxidant enzyme mimetics to apoptosis inhibitors and redox-active compound delivery systems, this work offers a scientifically rigorous reference for researchers and clinicians in pharmacology, toxicology, reproductive biology, and biomedical sciences. Its integrative approach supports both mechanistic understanding and the development of innovative therapeutic strategies aimed at redox modulation and cellular protection.

 

Author(s) Details

Abhishek Kumar
College of Veterinary and Animal Sciences (COVAS), Kishanganj-855107, India and Bihar Animal Sciences University, Patna, Bihar, India.

 

Please see the book here:- https://doi.org/10.9734/bpi/mono/978-81-990309-9-2