Arsenic toxicity: sources, pathophysiology and mechanism.

Background: Arsenic is a naturally occurring element that poses a significant threat to human health due to its widespread presence in the environment, affecting millions worldwide. Sources of arsenic exposure are diverse, stemming from mining activities, manufacturing processes, and natural geological formations. Arsenic manifests in both organic and inorganic forms, with trivalent meta-arsenite (As3+) and pentavalent arsenate (As5+) being the most common inorganic forms. The trivalent state, in particular, holds toxicological significance due to its potent interactions with sulfur-containing proteins. Objective: The primary objective of this review is to consolidate current knowledge on arsenic toxicity, addressing its sources, chemical forms, and the diverse pathways through which it affects human health. It also focuses on the impact of arsenic toxicity on various organs and systems, as well as potential molecular and cellular mechanisms involved in arsenic-induced pathogenesis. Methods: A systematic literature review was conducted, encompassing studies from diverse fields such as environmental science, toxicology, and epidemiology. Key databases like PubMed, Scopus, Google Scholar, and Science Direct were searched using predetermined criteria to select relevant articles, with a focus on recent research and comprehensive reviews to unravel the toxicological manifestations of arsenic, employing various animal models to discern the underlying mechanisms of arsenic toxicity. Results: The review outlines the multifaceted aspects of arsenic toxicity, including its association with chronic diseases such as cancer, cardiovascular disorders, and neurotoxicity. The emphasis is placed on elucidating the role of oxidative stress, genotoxicity, and epigenetic modifications in arsenic-induced cellular damage. Additionally, the impact of arsenic on vulnerable populations and potential interventions are discussed. Conclusions: Arsenic toxicity represents a complex and pervasive public health issue with far-reaching implications. Understanding the diverse pathways through which arsenic exerts its toxic effects is crucial to developing effective mitigation strategies and interventions. Further research is needed to fill gaps in our understanding of arsenic toxicity and to inform public health policies aimed at minimising exposure.Arsenic toxicity is a crucial public health problem influencing millions of people around the world. The possible sources of arsenic toxicity includes mining, manufacturing processes and natural geological sources. Arsenic exists in organic as well as in inorganic forms. Trivalent meta-arsenite (As3+) and pentavalent arsenate (As5+) are two most common inorganic forms of arsenic. Trivalent oxidation state is toxicologically more potent due to its potential to interact with sulfur containing proteins. Humans are exposed to arsenic in many ways such as environment and consumption of arsenic containing foods. Drinking of arsenic-contaminated groundwater is an unavoidable source of poisoning, especially in India, Bangladesh, China, and some Central and South American countries. Plenty of research has been carried out on toxicological manifestation of arsenic in different animal models to identify the actual mechanism of aresenic toxicity. Therefore, we have made an effort to summarize the toxicology of arsenic, its pathophysiological impacts on various organs and its molecular mechanism of action.

CRISPR/Cas9 system: a reliable and facile genome editing tool in modern biology.

Genome engineering has always been a versatile technique in biological research and medicine, with several applications. In the last several years, the discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 technology has swept the scientific community and revolutionised the speed of modern biology, heralding a new era of disease detection and rapid biotechnology discoveries. It enables successful gene editing by producing targeted double-strand breaks in virtually any organism or cell type. So, this review presents a comprehensive knowledge about the mechanism and structure of Cas9-mediated RNA-guided DNA targeting and cleavage. In addition, genome editing via CRISPR-Cas9 technology in various animals which are being used as models in scientific research including Non-Human Primates Pigs, Dogs, Zebra, fish and Drosophila has been discussed in this review. This review also aims to understand the applications, serious concerns and future perspective of CRISPR/Cas9-mediated genome editing.

Mechanisms and treatment strategies of organophosphate pesticide induced neurotoxicity in humans: A critical appraisal.

Organophosphates (OPs) are commonly used pesticides worldwide. Humans are exposed to OPs via different routes viz., the respiratory tract, gastrointestinal tract, and dermal integuments. OPs induce neuropathy by either phosphorylating acetyl cholinesterase or neuropathy target esterase, or by binding specifically to nicotinic or muscarinic receptors of nervous system. Other than neurobehavioral effects in humans, OPs cause cholinergic crisis, intermediate syndrome, OP-induced delayed neuropathy, and Chronic organophosphate-induced neuropsychiatric disorders in time and dosage dependent manner. Biomonitoring of OP markers from body fluids minimizes or measures the severity of the impact, allowing for timely control of the exposure. The standard treatments for OPs poisoning which avoid secondary organ damage are atropine administration, acetylcholine esterase restoration therapy with oximes, and general intensive care. This review summarizes the toxic manifestation data available on humans and discusses potential therapeutic modalities, with the aim to highlight the importance of increasing awareness about its potential risk and reevaluation of exposure level.

Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives.

Reactive oxygen and nitrogen species (RONS) are generated through various endogenous and exogenous processes; however, they are neutralized by enzymatic and non-enzymatic antioxidants. An imbalance between the generation and neutralization of oxidants results in the progression to oxidative stress (OS), which in turn gives rise to various diseases, disorders and aging. The characteristics of aging include the progressive loss of function in tissues and organs. The theory of aging explains that age-related functional losses are due to accumulation of reactive oxygen species (ROS), their subsequent damages and tissue deformities. Moreover, the diseases and disorders caused by OS include cardiovascular diseases [CVDs], chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases and cancer. OS, induced by ROS, is neutralized by different enzymatic and non-enzymatic antioxidants and prevents cells, tissues and organs from damage. However, prolonged OS decreases the content of antioxidant status of cells by reducing the activities of reductants and antioxidative enzymes and gives rise to different pathological conditions. Therefore, the aim of the present review is to discuss the mechanism of ROS-induced OS signaling and their age-associated complications mediated through their toxic manifestations in order to devise effective preventive and curative natural therapeutic remedies.