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
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