Unraveling snake venom phospholipase A2: an overview of its structure, pharmacology, and inhibitors

Sampat, Ganesh H.; Hiremath, Kashinath; Dodakallanavar, Jagadeesh; Patil, Vishal S.; Harish, Darasaguppe R.; Biradar, Prakash; Mahadevamurthy, Rashmi K.; Barvaliya, Manish; Roy, Subarna

doi:10.1007/s43440-023-00543-8

Cited by 8 publications

(2 citation statements)

References 159 publications

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“…It was established that the peculiarities of the blood supply of these organs are the cause of the probable extravasation of blood caused by viper toxins. S. Senthilkumaran et al [27] note that Daboia russelii viper venom contains protein components that have vasculotoxic, hemorrhagic, and proteolytic properties, cause the development of thrombocytopenia, and activate blood coagulation and fibrinolysis factors [21]. The consequence of this is the appearance of consumption coagulopathy and DICsyndrome.…”

Section: Discussionmentioning

confidence: 99%

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Analytical and quantitative assessment of the structural components of the adrenal glands of rats under the conditions of exposure to the venom of vipers Vipera berus berus and Vipera berus nikolskii

Niyazmetov,

Samborska,

Butska

et al. 2024

Rep. of Morph.

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Snakebite envenoming is a common but neglected public health problem worldwide, especially in tropical countries. Annual mortality as a result of snakebites exceeds 138,000. It is believed that this problem is underestimated, and in many countries, individual cases of bites are not subject to proper fixation. The purpose of the study is the analytical and quantitative assessment of the structural components of the rats' adrenal glands under exposure to the venom of Vipers Vipera berus berus and Vipera berus nikolskii. Experimental studies were carried out on white, non-linear male rats. Vipera berus berus and Vipera berus nikolskii viper venom were obtained from V. N. Karazin Kharkiv National University. The freeze-dried native venom was stored at -20 °C and dissolved in saline immediately before the experiment. The animals were divided into three groups (control and 2 experimental groups) of 10 individuals each. Experimental rats were injected intraperitoneally in a physiological solution with a semi-lethal dose (LD50) (1.576 mg/g-1) of Vipera berus berus and Vipera berus nikolskii venoms. Animals of the control group were injected intraperitoneally with only a physiological solution. Rats were removed from the experiment 24 hours after exposure to the poison and anesthetised by cervical dislocation. Statistical analysis of the area of the microcirculatory channel and the nuclear-cytoplasmic index was performed using Fiji: ImageJ program and processed in Excel. Administration of the venom of the vipers Vipera berus berus and Vipera berus nikolskii to rats was accompanied by a significant increase in the area of the microcirculatory bed relative to the control group (2.9 times for Vipera berus berus and 6.5 times for Vipera berus nikolskii). Exposure to Vipera berus berus viper venom was associated with a significant decrease in the nuclear-cytoplasmic index in rats of the experimental group compared to the control group (13 % and 42 %, respectively), which is evidence of a decrease in the area of the nuclei of endocrinocytes of the adrenal cortex. This indicator in rats under the administration of Vipera berus nikolskii venom was even lower and amounted to 12 %. According to the statistical analysis of the quantitative assessment of the state of the cortical substance of the adrenal glands, it is worth noting the similar effect of the poisons of both types of snakes at the cellular level. At the same time, at the tissue level, the effect of Vipera berus nikolskii venom is more pronounced than that of Vipera berus berus - this is evidenced by the higher degree of disruption of the structure of the hemomicrocirculatory channel in the adrenal cortex of animals from the group that was affected by this venom. It led to an increase in the area of vessels due to their expansion and ruptures of their walls and haemorrhages into the surrounding parenchyma and stroma.

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Section: Discussionmentioning

confidence: 99%

“…In recent years, scientists have reported the development of endocrine and metabolic disorders as a result of pituitary dysfunction, adrenal gland damage, dysglycemia, electrolyte disturbances, and renal tubular acidosis [21,26,36].…”

Section: Introductionmentioning

confidence: 99%

Analytical and quantitative assessment of the structural components of the adrenal glands of rats under the conditions of exposure to the venom of vipers Vipera berus berus and Vipera berus nikolskii

Niyazmetov,

Samborska,

Butska

et al. 2024

Rep. of Morph.

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Proteomic diversity of Russell's viper venom: exploring PLA2 isoforms, pharmacological effects, and inhibitory approaches

Srinivasan,

Nampoothiri,

Khandibharad

et al. 2024

Arch Toxicol

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Snakebite envenomation is a serious health concern in tropical regions, resulting in high mortality. The World Health Organization (WHO) has declared it a neglected tropical disease and is working on strategies to reduce mortality. Russell’s viper (Daboia russelii) is one of the most abundant venomous snakes found across Southeast Asia. Proteomic analysis of Russell’s viper venom has demonstrated variation, with phospholipase A2 (PLA2) being the most abundant toxin across geographic boundaries. PLA2, a major constituent of the low-molecular-weight fraction of snake venom, hydrolyses phospholipids at the sn-2 position, releasing arachidonic acid and lysophospholipids. They are reported to cause various pharmacological effects, including hemolysis, anticoagulation, neurotoxicity, myotoxicity, and oedema. Though administration of antivenoms (ASV) is the primary treatment for envenomation, it has many drawbacks. Besides causing hypersensitivity reactions and life-threatening anaphylaxis, treatment with ASV is further complicated due to its inability to neutralize low-molecular-weight toxins. Thus, there is a greater need to produce next-generation antivenoms that can target specific toxins in the venom. In this review, we explored the classification of Russell’s viper and the variation in its proteomic profile across Southeast Asia to date. In addition, we have also summarized the mechanism of action of PLA2 and discussed various isoforms of PLA2 found across different regions with their respective pharmacological effects. Finally, the drawbacks of commercially available antivenoms and the molecules investigated for inhibiting the low-molecular-weight toxin, PLA2 are discussed.

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Interrogation of three-finger toxin and phospholipase A2 higher order structures from the forest cobra (Naja melanoleuca) venom using a mass spectrometric approach

Wang,

Trim,

Truong

et al. 2024

International Journal of Mass Spectrometry

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Unraveling snake venom phospholipase A2: an overview of its structure, pharmacology, and inhibitors

Cited by 8 publications

References 159 publications

Analytical and quantitative assessment of the structural components of the adrenal glands of rats under the conditions of exposure to the venom of vipers Vipera berus berus and Vipera berus nikolskii

Analytical and quantitative assessment of the structural components of the adrenal glands of rats under the conditions of exposure to the venom of vipers Vipera berus berus and Vipera berus nikolskii

Proteomic diversity of Russell's viper venom: exploring PLA2 isoforms, pharmacological effects, and inhibitory approaches

Interrogation of three-finger toxin and phospholipase A2 higher order structures from the forest cobra (Naja melanoleuca) venom using a mass spectrometric approach

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