“Antimicrobial Resistance and Environmental Safety: Modern dialect” (Collection of Invited and Lead Papers, ISVPTCON-2024) provides a new horizon for the better understanding of the latest concept of biomedical research with special reference to modern molecular and analytical tools to address the modern approaches to mitigate the challenges in routine pharmacotherautics. This compilation has 26 chapters covering the impactful and acumen based concepts of scientific research approaches. Recent trends are highlighted in befitting manner. Different chapters emphasising the role of various receptor and their dynamicity with different ligands and their molecular cascade have been highlighted appropriately. This compilation also caters the need for reference handbook to the young biomedical researchers and scientists to enrich their scientific knowledge for the pursuit of better future. Moreover, this treatise also has the chapters focusing on regenerative medicine and traditional concepts of phytopharmacotherapy. This compilation covers the aspects of Artificial Intelligence (AI), Nitro vasodilators, Ion Channels and areas of modern Bioprospecting etc. Further, this book is published under the aegis of 24th Annual Conference of ISVPT held between 19-21 November 2024 at Department of Veterinary Pharmacology and Toxicology, DUVASU, Mathura.
Introduction Discovery of the antimicrobial agents in the early twentieth century was a breakthrough to safeguard the public health from the microbial infection. Propensity of these compounds to kill pathogens influenced the discovery of novel antimicrobials. However, since the 1970s, soon after the discovery of the fluoroquinolones, no major antibiotics have been introduced. The prevalent issue is largely attributed to the repercussions of antibiotic overuse or irresponsible utilization across diverse contexts, predominantly in clinical treatment, agricultural practices, animal healthcare, war crisis and the food system. Moreover, the accessibility and availability of antibiotics results in antimicrobial resistance (AMR). Nonprudent use of antibiotics accompanied by genetic plasticity allows microorganisms to adapt to the effect of antimicrobials causing a rapid surge of antimicrobial resistance. Extensive use of antimicrobials in animal husbandry is a major driver of AMR selection and the emergence of antimicrobial-resistant bacteria (ARBs) (World Health Organization, 2014).
Introduction Antimicrobial resistance (AMR) represents a critical public health crisis, with far-reaching implications for human, animal, and environmental health. If unchecked, by 2050, the global toll of AMR-related deaths could exceed 10 million, with Asia and Africa alone projected to account for approximately 4 million fatalities. In a potential ‘superbug’ outbreak scenario, the economic loss could reach as high as USD 100 trillion, especially impacting low- and middle income countries (LMICs) like India (O’Neill, 2014). AMR complicates the treatment of a wide array of infections, transforming previously manageable conditions into fatal threats. In 2019 alone, AMR was directly responsible for approximately 1.27 million deaths and contributed to an additional 5 million fatalities—surpassing the mortality rates of major infectious diseases such as HIV/AIDS and malaria (Murray et al., 2022). The urgency of addressing AMR is underscored by a World Bank report, which warns that unchecked AMR could cause a global GDP decline of 1.1% to 3.8% by 2050, and averting this scenario may require an estimated annual investment of around 9 billion USD (Aslam et al., 2024).
Buffalo farming offers a sustainable and economically viable solution to meet the growing demand for safe food production, particularly in regions with rising food insecurity. Buffaloes contribute around 45% of India’s total milk production and are more efficient in converting low-quality feed into high quality milk and meat, making them ideal for marginal farming environments. Buffalo milk, which has higher fat, protein, and mineral content than cow milk, is in demand for value-added dairy products, such as cheese, and fetches higher market prices. This enhances farmers’ incomes, especially small-scale dairy farmers, by ensuring higher returns on investment. Additionally, buffalo husbandry mitigates risks in crop failure due to climate change and provides sustainable employment opportunities. Furthermore, buffaloes produce less greenhouse gas emissions per unit of meat compared to cattle, making them more environmentally sustainable and climate smart. By advancing breeding practices and adopting scientific management, buffalo farming has the potential to drive the future of safe and sustainable food production, contributing significantly to food security and rural development.
Artificial Intelligence (AI), Machine Learning and Data Analytics seem to be invading all the fields to bring in efficiencies in those respective fields. However, Toxicology field seems to be lagging behind in these areas although there is a huge scope to use these advanced technologies. AI, data analytics and machine learning can be used for creating toxicology databases on chemicals, predictive modelling and AI for risk assessment, amongst other applications. One such effort was carried out for use of AI in creating a BOT, a ToxBot, for conducting risk assessments on chemicals which helped in gaining lot of efficiencies. The ToxBotwhich was created helped in conducting risk assessments and reducing time for such risk assessments from48 hours to 15 minutes. This also ensured using a uniform database, consistent output and helping toxicologists in arriving at unform conclusions. To begin with, the sponsors need to be very clear about the objective and expected outcome of the AI solution. The first step in creating these AI solutions is creation of a datasbase. While, creating AI solutions for risk assessment two aspects are important- source of Toxicology thresholds and the other one to derive exposure to population to assess safety. Creating a Toxicology data base for deriving thresholds is tedious. Toxicology studies generate huge data on multiple chemicals, drugs and botanicals. However, these data are scattered, not uniformly documented, and there is lack of efforts to compile them. Each constituent has data on each end point and these data are spread across multiple species. Hence the Toxicology data on each constituent has variables such as species, routes, doses, duration and end points. The efforts start with creating a complete Toxicological profile including all available data on each end point in each species by specific route of administration. These profiles then form the basis of a data base, which then enable to derive safety thresholds. The other database or system is to derive the exposure. This depends on the type of product, daily dose, frequency, route, concentration of chemical and the target population. These can be populated through an exposure matrix. For Al, these data need to be documented in uniform manner for subjecting it to Machine Learning and creating AI solutions. The AI experts would then be required to understand the entire process of the desired outcome and how the dataare used, at what points. This helps them in creating an algorithm. Once the algorithm and coding is created, the product is ready to be tested.
Use of Antimicrobial Agents The most frequently used classes of antimicrobial drugs in animals include tetracyclines, sulfonamides alone or in combination with potentiators, quinolones particularly fluoroquinolones, aminopenicillins alone as well as in combination with potentiators, first- and second-generation cephalosporins and also third- and fourth-generation cephalosporins, macrolides, and glycopeptides [1]. The “Terrestrial Animal Code”, issued by the Office International des Epizooties (OIE) in 2022 represents recent guidance for the responsible and prudent use of antimicrobials in veterinary medicine [2]. It describes the respective responsibilities of the competent authority and stakeholders in all processes pertaining to veterinary antimicrobial agents ranging from authorization to the administration to the animals.
GPCRs are integral membrane proteins that contain seven transmembrane (TM) α-helices, with a short cytoplasmic Helix 8 interconnected to the TM7 and the cytoplasmic C terminal. The amino terminal is extracellularly disposed. The 7 TM helices are interconnected by 3 extracellular and 3 intracellular loops. On the extracellular side between TM3 and TM4 is located a conserved disulphide bond. GPCRs being allosteric proteins, agonist binding at one site that is accessed from the extracellular space and termed the orthosteric site, promotes allosteric binding to another partner, a heterotrimeric G protein at the cytoplasmic side. Agonist binding not only promotes binding of the receptor to a G protein, but the affinity of the agonist for the receptor is increased by the G protein.
The Indian subcontinent has a vast costal belt along with the wide range of forest environment, which host large number of unexplored plant/marine species. This diversity has been the source of unique chemical compounds with the potential for industrial development as pharmaceuticals, cosmetics, nutritional supplements, molecular probes, fine chemicals and agrochemicals. In recent years, a significant number of novel metabolites with potent pharmacological properties have been discovered from the natural sources including marine and terrestrial plants. Recent move of society towards nature for the treatment of various diseases where there is no satisfactory cure in modern medicine has diverted the attention of natural/medicinal chemists and biologists to unravel their chemical characteristics and biological activities together in order to define their therapeutic potential in the light of modern pathobiological understandings. This move has led collectively to rediscover, design and refine the therapeutic application of medicinal plants/marine sources.
Post-traumatic bleeding, caused by accidents or battlefield injuries, is a major worldwide issue due to the associated high fatality rate. Significant efforts have been made to develop hemostatic medications that help reduce post-traumatic bleeding. The use of naturally abundant and highly biocompatible polymers, such as alginate, can have a substantial impact on the efficacy, safety and cost effectiveness of hemostatic medicines.We haveexaminedthe effectiveness of developed hemostatic hydrogel (SA-CZ) containing calcium (Ca2+) and zinc (Zn2+) in treating low-pressure bleeding wounds with the added benefit of promoting faster wound healing. The hydrogel nature of the hemostatic formulation poses limitation as hemostatic material due to its fluid absorption capability. Therefore, we converted the formulation in the form of dry formulation. Further, we explored the use of dry hemostatic particles (SA-CZ DHP) made from sodium alginate supplemented with Ca2+ and Zn2+ to manage excessive blood loss after post-traumatic hemorrhage.SA-CZ DHP showed substantial in-vitro efficacy, as observed by the significant reduction in coagulation time with better blood coagulation index (BCI) and no evident hemolysis in human blood. SA CZ also showed enhanced cellular migration (1.58-fold) in-vitroand improved wound closure (≈70%) as compared with betadine (≈38%) at the 7th-day post-wound creation in-vivo (p<0.005).The safe SA-CZ DHP showed high absorption and accelerated blood clotting kineticswith reduced coagulation time (≈70%, p<0.0001) in whole human blood. SA-CZ DHP significantlyreduced the mean blood loss (≈90% in SD rats tail incision), and bleeding time (≈60%in BALB/c mice tail incision) was at par with commercially available Celox™hemostatic granules.
The integration of pharmacology and bioinformatics has ushered in a new era of drug discovery and therapeutic innovati on, particularly in veterinary medicine. This interdisciplinary approach leverages computational tools to enhance the identification of drug targets, optimize treatment strategies, and address challenges such as antimicrobial resistance (AMR) and species specific drug metabolism. Pharmacogenomics, one of the most promising applications, allows for personalized medicine by tailoring drug therapies based on genetic variations in animals. Additionally, bioinformatics is revolutionizing vaccine development by identifying conserved antigens, aiding in the design of broad-spectrum and species-specific vaccines. In silico screening accelerates drug discovery by predicting drug-target interactions, reducing the time and cost of developing new veterinary therapies. Predictive modeling enables the simulation of disease progression and treatment outcomes, improving disease management. As bioinformatics technologies advance, they are poised to transform veterinary pharmacology, offering more precise and effective therapeutic options. This paper explores the synergies and applications of integrating pharmacology with bioinformatics to improve veterinary therapeutics, combat AMR, and accelerate drug discovery.
Antimicrobial drugs are important medicines which are continuously developed and evolveddue to the phenomenon of development of antimicrobial resistance to antimicrobial agents by microorganisms since the discovery of Penicillin by Sir Alexander Fleming in 1928-29. It has become essential for both pharmacologists and clinicians to optimize the certain principles of pharmacokinetic-pharmacodynamic aspects in both development of new antimicrobial drugs and in getting better therapeutic outcome in actual clinical situations in the field conditions to overcome the challenge thrown by microorganisms to the mankind. Pharmacokinetics (PK) describes the relationship between the dose of any drug given and the resulting concentration in the body. It includes the physiological process of absorption, distribution, metabolism and elimination whereas Pharmacodynamics (PD) describes the interaction between the drug concentration and pharmacological/therapeutic effect in vivo. It is determined as a definite concentration of a drugand its ability to kill or inhibit the cultured pathogenic microorganismin vitro that is aptly described asminimum inhibitory concentration (MIC) in case of antimicrobial drugs.
Animal models in diabetes research are very common when most of the existing models are developed as a conventional model either for Type 1 or for T2D. But very often a conventional model of diabetes cannot demonstrate the specific pathogenesis of diabetes related complications. Therefore, the necessity of the individual and specific model for diabetic complications has been raised in the recent years to achieve the authentic outcomes of specific research aims. A number of animal models of diabetic neuropathy have been developed in last few decades approaching from diverse point of views. However, most of them did not receive much popularity because of their considerable number of limitations and disadvantages. In a comprehensive review, Harati [4] reported that the major handicap in studying diabetic neuropathies is the lack of a suitable animal model that addresses acute and chronic events leading to diabetic neuropathy. Hence, in this review, the pathogenesis, advantages, disadvantages, and limitations of several genetic and nongenetic animal models of diabetic neuropathy have been discussed to substantiate their efficacy for human study and in order to guide diabetes research groups to more accurately select the most appropriate models to address their specific research questions.
Food Animals are the main protein source for human nutrition in the world.Sub-therapeutic doses of antibiotics are commonly used in food animal production, through their addition in feed and wateras antibiotic growth promoters (AGPs). Animal production is considered one of the main sources of antimicrobial resistances (AMR), thus the research for alternative strategies to the use of antibiotics in animal diet is essential to f ight the emergence of AMR. Currently, AMR causes the death of 700,000 people per year and it is forecasted that this will increase exponentially to 10 million by 2050, becoming the main cause of death worldwide.The reduction of antimicrobial resistance is a major challenge for the scientific community. In a few decades, infections by resistant bacteria are forecasted to be the main cause of death in the world. The withdrawal of antibiotics as growth promoters and their preventive use in animal production is essential to avoid these resistances, but this may impair productivity and health due to the increase in gut inflammation. The best alternative to Antibiotic growth promoters (AGPs) is a general improvement of conditions for food animals. In order to start a reformation of the Food Animal Industry as a whole, it’s essential to research to find out effective, resistance rare, low toxic and affordable alternatives to antibiotic growth promoters. Culinary herbs derived bioactives may be the promising products to address this challenge because it is traditionally proven to restore the gastrointestinal health due to beneficial effects on microbiota composition, mucosal barrier integrity, and immune system to control inflammation.
Dehydroepiandrosterone (DHEA) is known for many biological activities including potent cardioprotective properties. Meta analysis of human data strongly correlated diminished plasma level of DHEA with hypertension and age related anomalies and has been in clinical trial for efficacies against CVDs and hypertension. It was isolated for the first time in 1934 by Butenandt and Dannenbaum, later in 1944 extracted from human plasma (Oka et al., 2007). It is a 3β-hydroxysteroid, metabolized from pregnenolone, secreted from cells of zonareticulata of adrenal gland. Age-related decline in serum DHEA and DHEA-S(sulphate) is found to be associated with number of diseases including cardiovascular diseases, insulin resistance, cancer etc. (Arlt et al., 1999). Besides, DHEA dilates arteries, modulate hypoxia-induced vasoconstriction by activating potassium channels through soluble guanylatecyclase (sGC) activation, (Oka et al., 2007) and enhance endothelial function in particular via increasing nitric oxide synthesis (Haixian et al., 2019), induced relaxation in high K+ -induced contraction in thoracic aorta of rat embryo (Ochi et al., 2018). However, DHEA has never been explored as a vasorelaxant in mesenteric vascular bed, the major resistance bed of the circulatory system as well as its contribution in blockade of VDCC as possible mechanism for vasorelaxation. To date, the physiological role of DHEA in systemic vascular tissue as a vasorelaxant remains largely unknown and its potential use in the treatment of hypertension in human still remain inconclusive due to the increase in the risk of hormone driven cancer (Clark et al, 2018). Hence, we have chosen to explore the potential of DHEA as a vasorelaxant in conduit blood vessels like aorta and resistance blood vessels like mesenteric artery and elucidation of possible mechanism of vasorelaxation. Further, we also wanted to test the hypothesis whether in-vivo treatment of hypertensive rats with proven traditional medicine with known efficacy and acceptability could restore the level of DHEA in animal model of hypertension so as to have the beneficial effect of DHEA but without any adverse effect from external administration.
Nitrovasodilators are pharmaceutically key signalling molecule in the cardiovascular, immune and central nervous systems, and crucial steps in the regulation of NO bioavailability in health and diseases. These agents are well characterized and responsible for vasodilation by donation of nitric oxide (NO), and are principally employed for the treatment and prevention of angina pectoris, several cardiac diseases and regulation of vascular homeostasis (Carlstrom et al., 2024). NO has also been implicated in the pathology of many inflammatory diseases, including arthritis, myocarditis, colitis, and nephritis and a large number of pathologic conditions such as amyotrophic lateral sclerosis, cancer, diabetes, and neurodegenerative diseases. Several alternative strategies to increase NO signalling in the cardiovascular system have recently emerged, with promising therapeutic potential (Lundberg eta al., 2015). Nitroglycerin is commonly used in the treatment of angina pectoris because of its ability to decrease myocardial oxygen consumption. The use of nitroglycerin in the treatment of angina pectoris began not long after its original synthesis in 1847. Since then, the discovery of nitric oxide as a biological effector and better understanding of its roles in vasodilation, cell permeability, platelet function, inflammation, and other vascular processes have advanced our knowledge of the hemodynamic (mostly mediated through vasodilation of capacitance and conductance arteries) and nonhemodynamic effects of organic nitrate therapy, via both nitric oxide–dependent and –independent mechanisms (Divakaran and Loscalzo, 2017). These encompasses the identification of new pathways for enhancing NO synthase activity; ways to amplify the nitrate–nitrite–NO pathway; novel classes of NO-donating drugs; drugs that limit NO metabolism through effects on reactive oxygen species (Lundberg et al., 2015; Roy et al., 2023). Apart from the organic nitrates, direct activators of soluble guanylate cyclase, L-arginine, phosphodiesterase inhibitors and some other drugs also play critical role in vasoprotection (Gewaltig and Kojda, 2002).
Herbal medicines have become popular these days as complementary therapies for various disorders. These are available as single compounds, enriched extracts, or polyherbal preparations. The polyherbal formulations behave very differently as compared to the single compounds due to the interaction of different chemical constituents, present therein, with multiple receptors/targets in the biological system. The presence of the multiple chemical constituents is also likely to exhibit pharmacokinetic and metabolic interactions. Thus, it becomes difficult to monitor and predict the exact pharmacokinetic profile of all the chemical constituentspresent in a polyherbal formulation (He et al. 2011; Xie et al. 2012). As a result, pharmacokinetic studies of polyherbal formulations have been a long-standing hurdlein phytotherapy research. Conventional scientific approach for studying thepharmacological behaviour of a multicomponent therapy is to isolate the individualcompound and study the effect of these compounds on various targets and enzymes, independently. To rationalize the use of herbal medicines,a clear understanding of their pharmacokinetics and metabolism in the physiologicalsystem is required. A fundamental knowledge of pharmacokinetics of phytopharmaceuticals will be helpful inauthenticating their use.
Antibiotics serve as a backbone of modern clinical management but are currently facing serious threats from nosocomial and community emerging antimicrobial-resistance (AMR). The misuse and overuse of antibiotics and other antimicrobial agents in humans and animals have accelerated the development of resistant strains. Amongst the drug-resistant microbes, major threat is posed by the ESKAPEE group, an acronym for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli, comprising high to critical drug-resistant, World Health Organization Critical Priority I and II pathogens. The dry pipeline of effective and new antibiotics further exacerbates the situation with looming threat of heading to a ‘post-antibiotic era’. In such daring scenario of AMR, where AMR is expected to be the largest killer by 2050, it is imperative to understand the AMR development mechanism in bacteria as survival mechanism to find out way to mitigate AMR development and transfer.
Introduction to AI in Toxicology Toxicology is the scientific study of the adverse effects of chemical, physical, or biological agents on living organisms and the environment. It explores the mechanisms of toxicity, prevention, and mitigation, while applying this knowledge to safety evaluation and risk assessment of xenobiotics. It encompasses various sub-disciplines like chemical, organ-specific, genetic, environmental, and clinical toxicology, as well as toxicokinetic and regulatory risk assessment. Traditionally, toxicological assessments involve complex experimental models, including in vitro, in vivo, and clinical studies, which are time-consuming and resource-intensive. This is where AI steps in to revolutionize the field. Artificial Intelligence is a branch of computer science focused on developing systems capable of performing tasks that typically require human intelligence, such as learning, reasoning, and decision-making. Its subdomains—such as machine learning (ML), deep learning (DL), and natural language processing (NLP). In toxicology, AI, especially machine learning (ML), is applied to predict and evaluate chemical toxicokinetic and toxicity. ML uses algorithms to train computational models for problem-solving, and is categorized into supervised, unsupervised, and reinforcement learning methods. These AI techniques are increasingly utilized in toxicology for analyzing complex data and enhancing safety predictions. They are increasingly being used in various areas of toxicology, such as neurotoxicity, cardiovascular toxicology, nanotoxicology, toxicokinetic, dermal toxicity, and carcinogenesis. These approaches provide enhanced predictive and analytical capabilities across these diverse toxicological fields.AI methods can enhance in silico toxicology by integrating various data sources, including chemical structures, biological information, and in vitro results. This improves predictions of human toxicity, reducing the need for experimental studies, especially in vivo animal testing.
The art of Indian traditional knowledge regarding herbal medicine has a long history and can be considered as a potential source of new medicine. India has great potential in the market for herbal medicine, which is evident by the fact that medicinal plants required to prepare 50% of the drugs mentioned in the British Pharmacopoeia are reported to be present in the Western Himalayan region alone and India has approximately 8% of the world’s biodiversity, including plant genetic diversity with medicinal properties (Singh, 2006). Traditional medicine is widely used in rural areas, where 70% of the country’s population resides. Almost 75% of the medicinal plants grow naturally in different states of India. These plants are known to cure many ailments in animals. Ethno Veterinary Practices Ethno Veterinary Practices, also known as Traditional Veterinary Medicinal Practices are regarded as information gained over a period of time passed on from generation to generation. It is a community based functional knowledge system which has been developed, preserved and refined by generations of people through continuous interaction, observation and experimentation with their surrounding environment. Rural farmers mostly rely on ancestral ethno veterinary practices to deal with the diseases of their livestock and poultry. Veterinarians also show considerable interest in the medicinal plants, employed in traditional systems. This emerging trend in favour of herbal medicine is also due to the issues related to the antimicrobial drug resistance and drug residues in foods (milk/meat/eggs) of animal origin.
Introduction Pulmonary vascular tone regulation involves the balance between vasoconstriction and vasodilation, primarily controlled by pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (Lyle et al., 2017). This regulation is influenced by various factors, including ion channels, which modulates the flow of ions like K+, Ca2+, Na+ and Cl- across cell membranes, affecting vascular contraction and relaxation. Diseases like pulmonary artery hypertension (PAH) are attributed to dysregulation of vascular tone, which is essential for preserving ideal blood flow and pressure in the lungs (Christou and Khalil, 2022). Excessive vasoconstriction and impaired vasodilation increase pulmonary arterial pressure. This heightened resistance strains the right ventricle, leading to heart failure over time. Dysregulated ion channel movement in PASMCs is often a key factor in the development and progression of the disease. Ion channel receptors are promising candidates for medical therapy for the amelioration of pulmonary vascular disorders. Agents that regulate the functioning of ion channels may be employed to treat aberrant pulmonary blood vessel tone (Jouen-Tachoire et al., 2021).
Radiation combined injury (RCI) is complex condition that arises from simultaneous exposure to ionizing radiation and other types of physical trauma, such as blunt force injuries, thermal burns, or chemical exposure. This combination significantly complicates diagnosis and treatment, leading to increased morbidity and mortality. The past experiences of Hiroshima, Nagasaki, and Chernobyl have revealed that a large fraction of victims of such nuclear accidents or attacks suffer from combined radiation injuries. The possibility of a nuclear attack seems very far-fetched, but the destruction that would occur in such events will be massive, with a huge loss in terms of lives. Therefore, preparedness for the same should be done beforehand. Ionizing radiation damages cellular structures, primarily through direct ionization of DNA, leading to a range of acute and chronic health effects. The severity of radiation damage is influenced by the dose, type of radiation, and duration of exposure. Simultaneously, traumatic injuries can result from various mechanisms such as combat, accidents, explosions that may involve blunt trauma, lacerations, or burns. These injuries can lead to significant blood loss, organ failure, and infections, which may be aggravated by the immune suppression caused by radiation exposure. The interaction between radiation effects and traumatic injuries can create a unique clinical challenge, as each type of injury can exacerbate the other’s impact on the body. The pathophysiology and prognosis of RCI are more intricate and challenging to manage compared to simple burns, wound or radiation injuries. Although RCI is uncommon, it poses significant risks during unfortunate events like nuclear or radiological terrorist attacks and nuclear accidents. Historical nuclear incidents have shown that 65-70% of victims experienced varying degrees of thermal burns and other traumatic injuries alongside radiation exposure. These victims often sustain damage to nearly every organ system, particularly the gastrointestinal, cardiovascular, neurological, and hematopoietic systems, all crucial for survival.
Toxicological screening is essential for the development of new drugs (ND) and exploring the therapeutic potential of existing compounds.While animal testing is still regarded as the “gold standard” in traditional toxicity assessments, there is a growing need to transition towards alternative methods for drug safety testing. This shift is driven by the emergence of cutting-edge technologies and the adoption of the 3Rs principle (replace, reduce, refine) which emphasizes animal welfare.Routine in vitro safety screeningalong with GLP (Good Laboratory Practice) and non-GLP toxicity testing follow regulatory frameworks established by agencies such as the FDA (Food and Drug Administration), ICH (International Council for Harmonization)and EMA (European Medicines Agency) (Tang et al., 2023).In recent years, there has been a shift towards enhanced safety screening during the lead optimization stages of drug discovery. Regulatory toxicology testing plays a pivotal role in determining the potential risks associated with new drug compounds and ensuring their safety before they can proceed to human clinical trials and, ultimately, be marketed to the public.
Introduction Research in different fields of biological science requires test systems to observe the effects of chemicals or drugs. Testing new chemical entity (NCE) in drug discovery and development requires either in vitro or in vivo systems, including cell culture, tissue, organs and whole animal. Various advantages and disadvantages of each test system force scientists to find an alternative test system. The use of laboratory animals like rodents and non-rodents for evaluation of the effects of drugs or toxicity studies having ethical concerns. The cell-based and tissue-based test systems have various disadvantages including problem related prediction of the desirable and undesirable effects in animals. All such factors favor the use of laboratory animals like rats, mice, guinea pigs, rabbits, dogs, and primates in the pre-clinical phase of drug discovery. However, cost, manpower, and time-consuming efforts can be considered unfavorable for the use of such animals for testing every newly synthesized compound. Because of such difficulties in the field of new research with animal models, scientists made efforts to identify a newer animal model that can replace currently available animal species in research up to a certain extent. The animal model that is used in such drug discovery programs and toxicological testing must have homology to human beings or target species. The limitations or disadvantages of currently available animal models may be solved up to a certain level by using aquatic animal species like zebrafish.
Use of veterinary drugs in prevention, control and treatment is becoming inevitable with the intensification of livestock production system. Food animals given veterinary drugs contain residues of parent compounds and/ or their metabolites may remain in edible products for a period of time after treatment. In such scenario if withdrawal period of the drug is not observed, then there is every chance for that residue to become a part of the human diet. Subsequently, people consuming such veterinary drug residue-containing foods may suffer from different adverse health effects like increasing incidence of AMR, in addition to hypersensitivity and allergic reactions in some sensitive individuals. On the other hand, some veterinary drugs like nitrofurans and its metabolites (SEM, AHD, AOZ & AMOZ) represents major concern in food due to their carcinogenic nature and their use in food animals have been banned in most countries. Responsible and prudent use of veterinary drugs in food animals is must to promote animal health and to ensure food safety. On that front, veterinarians who is holding the prescription decision, indeed play a crucial role in the mission for attainment of judicious use of veterinary drugs in food producing animals and complying the regulatory requirement to produce safe animal sourced foods.
Role of Leptin in Uterine Function Leptin is a 16 kDa protein consisting of 167 amino acids, encoded by the LEP gene located on chromosome 7q31.3. Structurally, leptin comprises four anti parallel alpha helices (A, B, C, and D), two long loops (AB and CD), and a short loop (BC). It has three binding sites: site I is in the C-terminal region of helix D, site II spans the surface of helices A and C, and site III is located near the N-terminal region of helix D. Its structural similarity to proinflammatory cytokines such as interleukin-6 and granulocyte colony-stimulating factor suggests its potential immune-modulatory roles. Leptin’s effects on uterine contractions have been studied at length. In human uterine smooth muscle, leptin inhibits both spontaneous and oxytocin-induced contractions. Moynihan et al. (2008) reported that leptin caused a 46% reduction in spontaneous and a 42% reduction in oxytocin-induced contractions. A lesser degree of relaxation (36%) was noted in a larger study involving non-laboring human uterine tissue, while rat uterine tissue exhibited a 24% relaxation (Mumtaz et al., 2015). The concentrations used in these studies ranged from 1 nM to 1 µM, which includes the physiological range in pregnant women with normal body mass index (BMI). Leptin levels rise with increasing BMI during pregnancy (Hendler et al., 2005).
Vultures are obligate and highly efficient scavengers. They are keystone species providing important ecosystem services, but their adaptations to save energy, gorge themselves up to one third their body weight at a time, survive easily without food for up to a fortnight, conserve energy by using soaring and gliding flight, are just some of the unique and important characteristics of these magnificent birds. A highly efficient digestive system helps in extracting nutrients from otherwise non-nutrient sources like hide, tendons, and even bones. Vultures have been instrumental in keeping India clean and safe from disease outbreaks. A bird which is unaffected by multiple disease-causing micro-organisms helps to rid the environment from disease pandemics and epidemics. However, since the mid 1990ss these robust birds with a life span of 40-60 years, have declined drastically, from tens of millions to a few thousand currently, a decline of around 99%. For the formerly most abundant of these vultures, the white-rumped vulture, declines already happened by 99.9% in just 15 years! These declines led to multiple problems including increases in feral dog populations, economic and social losses and most importantly, 5,00,000 human deathsin five years,as a direct cause of the decline of vultures. The main cause of the vulture declines has been scientifically proven to be due to the use of veterinary diclofenac in cattle, their major source offood. Although veterinary diclofenac was banned since 2006, the drug has remained in the cattle carcasses at lower levels and new vulture toxic drugs have been discovered.
Spermatozoa, the male reproductive cells, play a crucial role in fertilization and subsequent embryonic development. However, toxic substances such as heavy metals(lead) can disrupt spermatozoa function through various mechanisms, including oxidative stress, DNA damage, and disruption of cellular homeostasis. The toxic effects can impair sperm motility, viability, and acrosomal integrity, ultimately leading to reduced fertility. Livestock are not immune to these toxic insults, which can compromise their reproductive efficiency and agricultural productivity. Lead (Pb) is a toxic pollutant and is extensively distributed in the environmental and biological systems. This topic envisages the detrimental effects of lead on spermatozoa functions, shedding light on the underlying mechanisms, signal transduction pathways, and sperm kinematic alterations.
The global herbal industry faces significant challenges due to varying regulatory frameworks, quality control standards, and traditional practices. This talk aims to bridge the gap by promoting “Herbal Harmony”- a unified approach to standardizing herbal products worldwide. Experts from diverse f ields will converge to discuss: Harmonization of regulatory frameworks, standardization of quality control and assurance, validation of traditional knowledge, innovative technologies for herbal analysis and global market trends and opportunities by fostering collaboration and knowledge sharing, “Herbal Harmony” seeks to: enhance consumer safety and confidence, promote sustainable herbal trade practices, support evidence-based herbal medicine and to facilitate international collaboration and trade.
