• The Korean Journal of Pharmacology
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• v.12 no.2 s.20
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• pp.33-41
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• 1976

Agkistrodon halys (Crotalidae) is the only species of poisonous snakes in Korea, and is divided into three subspecies; Agkistrodon bromhoffii brevicaudus, Agkistrodon calaginosus and Agkistrodon saxatilis. With the three venoms, the pharmacological actions on the cardiovascular system and intestine as well as some toxicological characteristics were studied. In addition, the precipitin test in an agar gel medium was employed for immunological comparison of the venoms and the sera of envenomed patients. The results obtained were as follows: Lyophilized venoms contained solids of $211{\sim}273mg/ml$, and LD50 to mice were 1.73 and 0.86 mg/kg in venoms of Agkistrodon bromhoffii brevicaudus obtained on July and October respectively, and 0.40 and 0.32 mg/kg in Agkistrodon calaginosus and the venoms of Agkistrodon saxatilis obtained on October was 2.29 mg/kg. Isoelectric focusing of lyophilized snake venoms showed 19 to 22 protein fractions and 2 to 3 isoamylase fractions. Acute irreversible hypotension was caused by the intravenous injection of large doses of venoms in rabbits and cats, but at the small doses, acute hypotension followed by slow recovery. Little changes of cardiac movements by the venom injection despite of marked hypotension were showed except bradycardia and arrhythmia prior the death. Also no changes on the isolated rabbit atria by the snake venoms were noted. The hypotensive effect of the snake venoms was prevented by the bilateral vagotomy or atropine pretreatment (1 mg/kg), but they did not affect when already the hypotension has undergone. In the isolated rabbit duodenum, small doses of venom increased the phasic movement, while large doses decreased after spastic contraction. With the injection of venoms in dog, strong contraction of gall-bladder was caused and it was not blocked by the pretreatment with phenoxybenzamine (10 mg/kg) or atropine (1.4 mg/kg). In the venoms of Agkistrodon bromhoffii brevicaudus and Agkistrodon calaginosus, at least 5 antigenic components were detected, and four of them were shared in common with each other. Polyvalent antivenin (Wyeth Lab. USA) had three common precipitating antibodies with the venom of Agkistrodon bromhoffii brevicaudus and Akistrodon calaginosus. In the serum of envenomed patients, no precipitating antibodies were seen to the venoms and little changes in serum protein, GOT and GPT were observed. In conclusion, the snake venoms obtained in Korea were highly toxic and caused chiefly the vascular collapse leading to death. This vascular collapse was resulted largely by cholinergic effects, and not cardiotoxin of venoms. In human, it is likely that precipitating antibodies to venom were not produced by an envenomed incidence to poisonous snakes.

• Archives of Pharmacal Research
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• v.20 no.1
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• pp.13-16
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• 1997

The cytotoxicity of animal venoms (snakes, insects and marine animals) was measured against SNU-1 (stomach cancer cells) by dye uptake assay (MTT method). And also L-amino acid oxidase (AAO) activity of the venoms was compared. Among them, the venom from Ophiophagus hannah (king cobra) showed a strong AAO activity as well as a high potent cytotoxicity. Cytotoxic protein having a AAO was then partially purified by HPLC-GPC and two fractions (Fr. I and Fr. II) were collected. The $IC_{50}$ values of Fr. I and Fr. II were 0.19 ${\mu}g/ml$ and 1.36 ${\mu}g/ml$, respectively. The results suggested that the cytotoxicity of king cobra venom may be due to its AAO activity.

• Journal of Pharmacopuncture
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• v.25 no.1
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• pp.52-62
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• 2022

Objectives: Snake venom is a complex mixture of various pharmacologically active substances, such as small proteins, peptides, and organic and mineral components. This paper aims to identify and analyse the proteins in common venomous snakes, such as Gloydius blomhoffii (G. blomhoffii) and Agkistrodon acutus (A. acutus), in Korea. Methods: We used mass spectrometry, electrophoresis, N-terminal sequencing and in-gel digestion to analyse the proteins in these two snake venoms. Results: We identified eight proteins in G. blomhoffii venom and four proteins in A. acutus venom. The proteins detected in G. blomhoffii and A. acutus venoms were phospholipase A₂, snake venom metalloproteinase and cysteine-rich secretory protein. Snake C-type lectin (snaclec) was unique to A. acutus venom. Conclusion: These data will contribute to the current knowledge of proteins present in the venoms of viper snakes and provide useful information for investigating their therapeutic potential.

• Journal of Society of Preventive Korean Medicine
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• v.20 no.1
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• pp.125-144
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• 2016

Objectives : About 13% of the medicines used by traditional korean medicines(TKM), are called animal medicines and are derived from non-herbal sources such as animals and insects. However, the clinical use of these preparations from animal medicines is often based on tradition and belief, rather than on evidence of toxicity and efficacy. As a result, animal medicines containing toxin have caused serious problems from injecting patients with venom. Here, various venoms frequently used as TKM were reviewed in terms of their instinct toxity and tried to estimate their safety classification. Methods : The estimation of safety classification was based on human equivalent dose(HED)-based MOS (margin of safety) and clinical dose applied for patients. Results and Conclusions : Except that of snake venom due to no clinical dose, they were evaluated as class 3 for bee venom, class 4 for cantharidin, toxin from blister beetle, and class 1 for venom from scolopendrid. In conclusion, animal medicines showed a wide range of safety classification from class 1 to class 4. This wide range is estimated to result from extremely limited applications of each venom for patients because of their strong toxicity. However, it should be cautious for application in clinics since animal medicines can produce anaphylactic reactions particularly after veinous administration even with a tiny amount of venom.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4855-4860
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• 2012

Since cancer is one of the leading causes of death worldwide, and there is an urgent need to find better treatment. In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. Treatment modalities comprise radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Currently, the use of chemotherapeutics remains the predominant option for clinical control. However, one of the major problems with successful cancer therapy using chemotherapeutics is that patients often do not respond or eventually develop resistance after initial treatment. This has led to the increased use of anticancer drugs developed from natural resources. The biodiversity of venoms and toxins makes them a unique source from which novel therapeutics may be developed. In this review, the anticancer potential of snake venom is discussed. Some of the included molecules are under clinical trial and may find application for anticancer drug development in the near future.

• Journal of The Korean Society of Clinical Toxicology
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• v.16 no.1
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• pp.57-59
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• 2018

Severe systemic responses including neurologic complications such as myasthenia gravis, myeloradiculopathy, optic neuropathy, parkinsonism, stroke and Guillain-$barr{\acute{e}}$ syndrome can occur after bee stings. This case describes a 78-year-old female who presented with symptoms of acute progressive bilateral symmetrical weakness in both lower legs after multiple bee stings. Nerve conduction study findings were consistent with acute sensorimotor axonal neuropathy and recovered by treatment with intravenous immunoglobulin. This case highlights that bee stings can result in acute onset Guillain-$barr{\acute{e}}$ syndrome, although the pathophysiologies of bee venoms need to be investigated accurately.

• Parasites, Hosts and Diseases
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• v.54 no.4
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• pp.415-421
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• 2016

The drug-resistance of malaria parasites is the main problem in the disease control. The huge Brazilian biodiversity promotes the search for new compounds, where the animal kingdom is proving to be a promising source of bioactive compounds. The main objective of this study was to evaluate the antiplasmodial and cytotoxic activity of the compounds obtained from the toad venoms of Brazilian Amazon. Toad venoms were collected from the secretion of Rhinella marina and Rhaebo guttatus in Mato Grosso State, Brazil. The powder was extracted at room temperature, yielding 2 extracts (RG and RM) and a substance ('1') identified as a bufadienolide, named telocinobufagin. Growth inhibition, intraerythrocytic development, and parasite morphology were evaluated in culture by microscopic observations of Giemsa-stained thin blood films. Cytotoxicity was determined against HepG2 and BGM cells by MTT and neutral red assays. The 2 extracts and the pure substance ('1') tested were active against chloroquine-resistant Plasmodium falciparum strain, demonstrating lower $IC_{50}$ values. In cytotoxic tests, the 2 extracts and substance '1' showed pronounced lethal effects on chloroquine-resistant P. faciparum strain and low cytotoxic effect, highlighting toad parotoid gland secretions as a promising source of novel lead antiplasmodial compounds.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4753-4758
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• 2014

In recent times, a number of studies have provided evidence that biotoxins present great potential as antitumor agents, such as snake venom, bee venom, some bacteria toxins and plant toxins, and thus could be used as chemotherapeutic agents against tumors. The biodiversity of venoms and toxins make them a unique source from which novel anticancer agent may be developed. Biotoxins, also known as natural toxins, include toxic substances produced by plants, animals and microorganisms. Here, we systematically list representative biological toxins that have antitumor properties, involving animal toxins, plant toxins, mycotoxins as well as bacterial toxins. In this review, we summarize the current knowledge involving biotoxins and the active compounds that have anti-cancer activity to induce cytotoxic, antitumor, immunomodulatory, and apoptotic effects in different tumor cells in vivo or in vitro. We also show insights into the molecular and functional evolution of biotoxins.

• Journal of Pharmacopuncture
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• v.25 no.2
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• pp.114-120
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• 2022

Objectives: Antivenom serums have been used extensively for over a century and are the only effective treatment option for snake bites and other dangerous animal envenomations. In therapeutic serum centers, a wide range of antivenoms is made from animal serum, mainly equine and sheep, that are immunized with single or multiple venoms. This work aimed to use caprylic acid (CA) to purify therapeutic snake antivenom. Methods: Plasma was obtained from equine immunized with a mixture of venoms. Immunized plasma was obtained by precipitation of different concentrations (2-5%) of CA. This methodology was compared to that based on ammonium sulfate (AS) precipitation. Sediment plasma proteins were purified by ion-exchange chromatography. Protein assay, SDSPAGE, and agar gel diffusion were performed. Results: The total protein precipitation with AS was higher than precipitation with CA, but the best results were obtained when CA was added to the plasma until a final CA concentration of 5% was reached. Chromatography and electrophoresis indicated a stronger band for the 5% CA, and the gel diffusion assay showed antigen-antibody interaction in the purified serum. Conclusion: The use of CA compared to the routine method for purifying hyperimmune serums is a practical and cost-effective method for preparing and producing therapeutic serums. It constitutes a potentially valuable technology for alleviating the critical shortage of antivenom in Iran.

• Korean journal of applied entomology
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• v.46 no.2
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• pp.229-234
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• 2007

Pure Bombus ignitus venom samples were submitted to two-dimensional gel electrophoresis. A total of 64 excised spots were analyzed by mass spectrometry. Three main proteins resulted in the identification have not been described in other bee venoms before. Dose-dependence against human carcinoma (Hep3B, BT-20, A549 and AGS) were observed from 1ng/ml to 100ng/ml. Expecially, the treatment of 100ng/ml B. ignitus venoms showed the highest cytotoxicity with 55% against hepatocellular carcinoma (Hep3B). The B. ignitus venoms showed strong antimicrobial activities against Enterococcus faecium and Shigella sonnei, and practically antimicrobial activity against the other microorganisms tested. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of E. faecium and S. sonnei, were 0.256ug/ml, respectively.