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Papers by Amit Talukdar
Toxicon, 2024
Bungarus fasciatus also referred to as the Banded krait is a snake which possesses venom and belo... more Bungarus fasciatus also referred to as the Banded krait is a snake which possesses venom and belongs to the Elapidae family. It is widely distributed across the Indian subcontinent and South East Asian countries and is responsible for numerous snakebites in the population. B. fasciatus possesses a neurotoxic venom and envenomation by the snake results in significant morbidity and occasional morbidity in the victim if not treated appropriately. In this study, the efficacy of Indian polyvalent antivenom (Premium Serums polyvalent antivenom) was evaluated against the venom of B. fasciatus from Guwahati, Assam (India) employing the Third-generation antivenomics technique followed by identification of venom proteins from three poorly immunodepleted peaks (P5, P6 and P7) using LC-MS/MS analysis. Seven proteins were identified from the three peaks and all these venom proteins belonged to the phospholipase A2 (PLA2) superfamily. The identified PLA2 proteins were corroborated by the in vitro enzymatic activities (PLA2 and Anticoagulant activity) exhibited by the three peaks and previous reports of pathological manifestation in the envenomated victims. Neutralization of enzymatic activities by Premium Serums polyvalent antivenom was also assessed in vitro for crude venom, P5, P6 and P7 which revealed moderate to poor inhibition. Inclusion of venom proteins/peptides, which are non-immunodepleted or poorly immunodepleted, into the immunization mixture of venom used for antivenom production may help in enhancing the efficacy of the polyvalent antivenom.
Molecular Biology Reports, 2023
Introduction: Diabetic nephropathy (DN), an outcome of prolonged diabetes, has affected millio... more Introduction:
Diabetic nephropathy (DN), an outcome of prolonged diabetes, has affected millions of people worldwide and every year the incidence and prevalence increase substantially. The symptoms may start with mild manifestations of the disease such as increased albuminuria, serum creatinine levels, thickening of glomerular basement membrane, expansion of mesangial matrix to severe pathological symptoms such as glomerular lesions and tubulointerstitial fibrosis which may further proceed to cardiovascular dysfunction or end-stage renal disease.
Perspective:
Numerous therapeutic interventions are being explored for the management of DN, however, these interventions do not completely halt the progression of this disease and hence animal models are being explored to identify critical genetic and molecular parameters which could help in tackling the disease. Rodent models which mostly include mice and rats are commonly used experimental animals which provide a wide range of advantages in understanding the onset and progression of disease in humans and also their response to a wide range of interventions helps in the development of effective therapeutics. Rodent models of type 1 and type 2 diabetes induced DN have been developed utilizing different platforms and interventions during the last few decades some of which mimic various stages of diabetes ranging from early to later stages. However, a rodent model which replicates all the features of human DN is still lacking. This review tries to evaluate the rodent models that are currently available and understand their features and limitations which may help in further development of more robust models of human DN.
Conclusion:
Using these rodent models can help to understand different aspects of human DN although further research is required to develop more robust models utilizing diverse genetic platforms which may, in turn, assist in developing effective interventions to target the disease at different levels.
Journal of Proteins and Proteomics, 2022
Bungarus fasciatus is one of the medically important elapid snakes of South and South-eastern Asi... more Bungarus fasciatus is one of the medically important elapid snakes of South and South-eastern Asia and is responsible for several snakebite incidents some of which were fatal. In this study, the venom compositional variation of Bungarus fasciatus from three different geographical locations in eastern and north-east India: two adjacent villages of Hooghly (West Bengal), Aizawl (Mizoram) and Guwahati (Assam) are reported. In vitro biochemical assays exhibit variation in phospholipase A2 activity, fibrinogenolytic activity, caseinolytic activity and anti-coagulation activity. The immunoreactivity of three Indian
polyvalent antivenoms against the venoms revealed incomplete recognition. Bharat Serums antivenom demonstrated that at a venom–antivenom ratio of 1:16, the antivenom exhibited different immunocapturing abilities for all the venom samples. The percentage of non-retained fractions was highest for Guwahati (60.00%) and lowest for Hooghly 1 (18.91%). The study demonstrates intra-population (or inter-individual) variation of B. fasciatus venom from two nearby locations of Hooghly (West Bengal), intra-specific variation of B. fasciatus from three geographical locations and also inter-specific venom variation with B. caeruleus from Tamil Nadu. Thus, the venom variation leads to partial immune cross-reactivity by Indian polyvalent antivenoms. Inclusion of non-recognized venom proteins in the immunization mixture during antivenom production would help to improve the efficacy of the antivenom. Further study of the neutralizing ability of Indian polyvalent antivenoms against medically important snakes from different geographical regions would help to understand the effectiveness of the
antivenoms and would invariably assist in the designing and development of safe and effective antivenoms.
Toxin Reviews, 2023
Snake venom is a blend of bioactive proteins, polypeptides, and various other substances with tox... more Snake venom is a blend of bioactive proteins, polypeptides, and various other substances with toxic and lethal properties that are known to modulate varied physiological and biological systems. During envenomation, venom toxins primarily target the hemostatic and nervous system for effective immobilization or death of the prey. The central (CNS) and the peripheral nervous system (PNS) are targeted through neuroreceptors, synaptic membranes, and critical ion channels, and some of these toxins also penetrate the blood-brain barrier. Despite its vital role and influence on the central nervous system, there exist limited information on the role of venom proteins and peptides associated with the manifestations of neurotoxicity. This review attempts to update the reader on the mechanism of direct and indirect interactions of snake venom protein (s) in the central nervous system as well as its effects on the physiology and behavior of the envenomated prey. Further, the role of these snake venom peptides in the field of neuropathic pain and neurodegenerative diseases has been reviewed for their therapeutic potential. Future investigations may provide valuable information to study the detailed mechanisms of
such interactions to identify novel targets for the development of therapeutic interventions.
Books by Amit Talukdar
Emerging Trends in Life Sciences. Volume-I, 2022
Neurodegenerative diseases affect millions of people worldwide and are responsible for the loss o... more Neurodegenerative diseases affect millions of people worldwide and are responsible for the loss of specific neurons in the central nervous system. These diseases include a wide range of neurological disorders like Alzheimer's disease, Parkinson's disease, Multiple sclerosis etc. and are caused by a wide range of processes like aggregate deposition, oxidative stress, inflammation, immune activation, dysfunctional mitochondria and apoptosis. Most of the treatments and drugs available are symptomatic treatments and hence researchers have tried to identify molecules to inhibit or interfere with these events and to limit or halt the pathogenesis of these diseases. Snake venoms are a storehouse of natural proteins which have specific targets in the biological system. Researchers have tried to explore these snake venom toxins to ameliorate various pathophysiological conditions associated with various neurodegenerative diseases. This chapter describes the pathophysiological and clinical symptoms of some of the neurodegenerative diseases and the advances made in research for using various snake venom toxins or synthetic molecules derived from snake venom toxins for treatment of these diseases. The role of snake venom toxins in neuritogenesis is also discussed along with other advances in this field. Further research is required for the identification of more such toxins and their development into effective drugs.
Thesis Chapters by Amit Talukdar
Tezpur University, 2024
Kraits belong to the genus Bungarus which form an important group of snakes in India (around 12 t... more Kraits belong to the genus Bungarus which form an important group of snakes in India (around 12 to 14 known species) and belong to the Elapidae family. One of these kraits, Bungarus fasciatus, is commonly found in the Eastern and North-East regions of India, although they have been reported from other parts of the country as well. Their general distribution ranges from the Indian subcontinent to the South-East Asian countries and Southern China and they have been recorded at an altitude as high as 5000 m above sea level. B. fasciatus can be easily identified from its alternating yellow and black bands of equal width encircling throughout its body and it is mostly active at the night. It feeds mainly on the small fish, frog, skinks, eggs of snake and is also known to feed on other snakes as well.
Snakebite envenomation is considered as a neglected tropical disease which is responsible for thousands of death and permanent disability every year in victims worldwide. The venom of snakes is a mixture of several toxins which are pharmacologically active and has evolved over millions of years for the purpose of offence and defense. B. fasciatus is of WHO ‘Category 2’ medical importance consisting of neurotoxic venom and is responsible for occasional snakebite incidents in this region, some even leading to death of the victim. Bite from B. fasciatus may cause little to no pain in humans and a minimum local damage to tissue, however, since the venom contains both pre-synaptic and post-synaptic neurotoxins their symptoms become progressively evident with time. Systematic symptoms may include a rapid or delayed progressive respiratory paralysis.
Antivenom serves as the only medically viable option for treating snake envenomation effectively. In India, polyvalent antivenom, which are raised against the venom pool of the “Big-Four” snakes, are mainly used to treat snake envenomation cases including bites from B. fasciatus. Although polyvalent antivenom provides some degree of paraspecific protection from B. fasciatus envenomation, however, due to inter-species venom variation between B. caeruleus and B. fasciatus, these antivenom are not fully effective due to which a high dose is often administered by healthcare professionals. Intra-species venom variation among B. fasciatus venom from different geographical locations may affect the antivenom efficacy. A high antivenom dosage may lead to adverse side-effects
such as serum sickness and anaphylactic reactions in the victims. Hence, studying thevenom variation in B. fasciatus venom from different locations of Eastern and North- East India and their cross-reactivity to different Indian polyvalent antivenom becomes necessary to understand the efficacy of these antivenom, and also to identify non-immunodepleted and poorly-immunodepleted venom proteins.
The different aspects of the study are documented in this thesis and organized into six chapters.
Toxicon, 2024
Bungarus fasciatus also referred to as the Banded krait is a snake which possesses venom and belo... more Bungarus fasciatus also referred to as the Banded krait is a snake which possesses venom and belongs to the Elapidae family. It is widely distributed across the Indian subcontinent and South East Asian countries and is responsible for numerous snakebites in the population. B. fasciatus possesses a neurotoxic venom and envenomation by the snake results in significant morbidity and occasional morbidity in the victim if not treated appropriately. In this study, the efficacy of Indian polyvalent antivenom (Premium Serums polyvalent antivenom) was evaluated against the venom of B. fasciatus from Guwahati, Assam (India) employing the Third-generation antivenomics technique followed by identification of venom proteins from three poorly immunodepleted peaks (P5, P6 and P7) using LC-MS/MS analysis. Seven proteins were identified from the three peaks and all these venom proteins belonged to the phospholipase A2 (PLA2) superfamily. The identified PLA2 proteins were corroborated by the in vitro enzymatic activities (PLA2 and Anticoagulant activity) exhibited by the three peaks and previous reports of pathological manifestation in the envenomated victims. Neutralization of enzymatic activities by Premium Serums polyvalent antivenom was also assessed in vitro for crude venom, P5, P6 and P7 which revealed moderate to poor inhibition. Inclusion of venom proteins/peptides, which are non-immunodepleted or poorly immunodepleted, into the immunization mixture of venom used for antivenom production may help in enhancing the efficacy of the polyvalent antivenom.
Molecular Biology Reports, 2023
Introduction: Diabetic nephropathy (DN), an outcome of prolonged diabetes, has affected millio... more Introduction:
Diabetic nephropathy (DN), an outcome of prolonged diabetes, has affected millions of people worldwide and every year the incidence and prevalence increase substantially. The symptoms may start with mild manifestations of the disease such as increased albuminuria, serum creatinine levels, thickening of glomerular basement membrane, expansion of mesangial matrix to severe pathological symptoms such as glomerular lesions and tubulointerstitial fibrosis which may further proceed to cardiovascular dysfunction or end-stage renal disease.
Perspective:
Numerous therapeutic interventions are being explored for the management of DN, however, these interventions do not completely halt the progression of this disease and hence animal models are being explored to identify critical genetic and molecular parameters which could help in tackling the disease. Rodent models which mostly include mice and rats are commonly used experimental animals which provide a wide range of advantages in understanding the onset and progression of disease in humans and also their response to a wide range of interventions helps in the development of effective therapeutics. Rodent models of type 1 and type 2 diabetes induced DN have been developed utilizing different platforms and interventions during the last few decades some of which mimic various stages of diabetes ranging from early to later stages. However, a rodent model which replicates all the features of human DN is still lacking. This review tries to evaluate the rodent models that are currently available and understand their features and limitations which may help in further development of more robust models of human DN.
Conclusion:
Using these rodent models can help to understand different aspects of human DN although further research is required to develop more robust models utilizing diverse genetic platforms which may, in turn, assist in developing effective interventions to target the disease at different levels.
Journal of Proteins and Proteomics, 2022
Bungarus fasciatus is one of the medically important elapid snakes of South and South-eastern Asi... more Bungarus fasciatus is one of the medically important elapid snakes of South and South-eastern Asia and is responsible for several snakebite incidents some of which were fatal. In this study, the venom compositional variation of Bungarus fasciatus from three different geographical locations in eastern and north-east India: two adjacent villages of Hooghly (West Bengal), Aizawl (Mizoram) and Guwahati (Assam) are reported. In vitro biochemical assays exhibit variation in phospholipase A2 activity, fibrinogenolytic activity, caseinolytic activity and anti-coagulation activity. The immunoreactivity of three Indian
polyvalent antivenoms against the venoms revealed incomplete recognition. Bharat Serums antivenom demonstrated that at a venom–antivenom ratio of 1:16, the antivenom exhibited different immunocapturing abilities for all the venom samples. The percentage of non-retained fractions was highest for Guwahati (60.00%) and lowest for Hooghly 1 (18.91%). The study demonstrates intra-population (or inter-individual) variation of B. fasciatus venom from two nearby locations of Hooghly (West Bengal), intra-specific variation of B. fasciatus from three geographical locations and also inter-specific venom variation with B. caeruleus from Tamil Nadu. Thus, the venom variation leads to partial immune cross-reactivity by Indian polyvalent antivenoms. Inclusion of non-recognized venom proteins in the immunization mixture during antivenom production would help to improve the efficacy of the antivenom. Further study of the neutralizing ability of Indian polyvalent antivenoms against medically important snakes from different geographical regions would help to understand the effectiveness of the
antivenoms and would invariably assist in the designing and development of safe and effective antivenoms.
Toxin Reviews, 2023
Snake venom is a blend of bioactive proteins, polypeptides, and various other substances with tox... more Snake venom is a blend of bioactive proteins, polypeptides, and various other substances with toxic and lethal properties that are known to modulate varied physiological and biological systems. During envenomation, venom toxins primarily target the hemostatic and nervous system for effective immobilization or death of the prey. The central (CNS) and the peripheral nervous system (PNS) are targeted through neuroreceptors, synaptic membranes, and critical ion channels, and some of these toxins also penetrate the blood-brain barrier. Despite its vital role and influence on the central nervous system, there exist limited information on the role of venom proteins and peptides associated with the manifestations of neurotoxicity. This review attempts to update the reader on the mechanism of direct and indirect interactions of snake venom protein (s) in the central nervous system as well as its effects on the physiology and behavior of the envenomated prey. Further, the role of these snake venom peptides in the field of neuropathic pain and neurodegenerative diseases has been reviewed for their therapeutic potential. Future investigations may provide valuable information to study the detailed mechanisms of
such interactions to identify novel targets for the development of therapeutic interventions.
Emerging Trends in Life Sciences. Volume-I, 2022
Neurodegenerative diseases affect millions of people worldwide and are responsible for the loss o... more Neurodegenerative diseases affect millions of people worldwide and are responsible for the loss of specific neurons in the central nervous system. These diseases include a wide range of neurological disorders like Alzheimer's disease, Parkinson's disease, Multiple sclerosis etc. and are caused by a wide range of processes like aggregate deposition, oxidative stress, inflammation, immune activation, dysfunctional mitochondria and apoptosis. Most of the treatments and drugs available are symptomatic treatments and hence researchers have tried to identify molecules to inhibit or interfere with these events and to limit or halt the pathogenesis of these diseases. Snake venoms are a storehouse of natural proteins which have specific targets in the biological system. Researchers have tried to explore these snake venom toxins to ameliorate various pathophysiological conditions associated with various neurodegenerative diseases. This chapter describes the pathophysiological and clinical symptoms of some of the neurodegenerative diseases and the advances made in research for using various snake venom toxins or synthetic molecules derived from snake venom toxins for treatment of these diseases. The role of snake venom toxins in neuritogenesis is also discussed along with other advances in this field. Further research is required for the identification of more such toxins and their development into effective drugs.
Tezpur University, 2024
Kraits belong to the genus Bungarus which form an important group of snakes in India (around 12 t... more Kraits belong to the genus Bungarus which form an important group of snakes in India (around 12 to 14 known species) and belong to the Elapidae family. One of these kraits, Bungarus fasciatus, is commonly found in the Eastern and North-East regions of India, although they have been reported from other parts of the country as well. Their general distribution ranges from the Indian subcontinent to the South-East Asian countries and Southern China and they have been recorded at an altitude as high as 5000 m above sea level. B. fasciatus can be easily identified from its alternating yellow and black bands of equal width encircling throughout its body and it is mostly active at the night. It feeds mainly on the small fish, frog, skinks, eggs of snake and is also known to feed on other snakes as well.
Snakebite envenomation is considered as a neglected tropical disease which is responsible for thousands of death and permanent disability every year in victims worldwide. The venom of snakes is a mixture of several toxins which are pharmacologically active and has evolved over millions of years for the purpose of offence and defense. B. fasciatus is of WHO ‘Category 2’ medical importance consisting of neurotoxic venom and is responsible for occasional snakebite incidents in this region, some even leading to death of the victim. Bite from B. fasciatus may cause little to no pain in humans and a minimum local damage to tissue, however, since the venom contains both pre-synaptic and post-synaptic neurotoxins their symptoms become progressively evident with time. Systematic symptoms may include a rapid or delayed progressive respiratory paralysis.
Antivenom serves as the only medically viable option for treating snake envenomation effectively. In India, polyvalent antivenom, which are raised against the venom pool of the “Big-Four” snakes, are mainly used to treat snake envenomation cases including bites from B. fasciatus. Although polyvalent antivenom provides some degree of paraspecific protection from B. fasciatus envenomation, however, due to inter-species venom variation between B. caeruleus and B. fasciatus, these antivenom are not fully effective due to which a high dose is often administered by healthcare professionals. Intra-species venom variation among B. fasciatus venom from different geographical locations may affect the antivenom efficacy. A high antivenom dosage may lead to adverse side-effects
such as serum sickness and anaphylactic reactions in the victims. Hence, studying thevenom variation in B. fasciatus venom from different locations of Eastern and North- East India and their cross-reactivity to different Indian polyvalent antivenom becomes necessary to understand the efficacy of these antivenom, and also to identify non-immunodepleted and poorly-immunodepleted venom proteins.
The different aspects of the study are documented in this thesis and organized into six chapters.