The peptide fraction of Bothrops jararaca snake venom induces toxicological effects on the male reproductive system after local envenomation in mice

Bothrops envenomation is complex and provokes prominent local tissue damage and systemic disturbances,but little is known about their effects on the male reproductive system.After intratesticular injection,the bioactive peptide fraction(Bj-PF)obtained from Bothrops jararaca snake venom changes the structure of different stages of the seminiferous epithelium cycle in adult mice.For the first time,we investigated whether local envenomation of Bj-PF induces toxicological effects on the male reproductive system,particularly on the seminiferous epithelium and Sertoli cells.Male adult mice were treated with 0.24 mg.kg^(-1) by intramuscular(i.m.)injection for 24 h.The testes samples were collected for morphological and morphometric evaluation.The toxicological effects of Bj-PF were also analyzed on mitochondrial metabolism and nitrite(NO2)production in 15P-1 Sertoli cell culture.Bj-PF changed the structure and function of the seminiferous epithelium,particularly the disruption of the epithelium and the presence of degenerated germ cells in the adluminal compartment,but there were no alterations in the basal compartment.Bj-PF increased the thickness of the seminiferous epithelium and decreased the lumen diameter of the tubule.Semiquantitative histological assessment of the degree of tubule degeneration revealed that Bj-PF also increased the number of hypospermatogenic tubules compared to control.Bj-PF reduced NO2 levels in 15P-1 Sertoli cells without changing the mitochondrial metabolism.Overall,the fact that Bj-PF alters the structure and function of the seminiferous epithelium suggests that bioactive peptides found in B.jararaca snake venom can have toxicological effects on the reproductive systems of affected male mice,providing new insight into the biological characteristics of snake venom and therapeutic strategies for envenomation inflammation.

Effect of Purified Paper Wasp Ropalidia marginata Venom Toxins on Different Biomolecules in Mice Serum

This study evaluated the effects of purified paper wasp Ropalidia marginata venoms on various biomolecules in the blood serum of albino mice. Changes in the concentration of some important macromolecules, i.e., proteins, free amino acids, uric acid, cholesterol, pyruvic acid, total lipids and glucose were noted down. These alterations were measured after intraperitoneal injection of 40% and 80% 24-hour LD50 purified Ropalidia marginata venom toxin. Serum total protein levels were found to decrease to 78% after 6 hrs, while serum free amino acid levels were significantly increased to 117% 6 hrs after venom injection compared to control. It was also found that serum uric acid levels increased to 138% after 8 hrs of venom injection compared to control. The increase in serum cholesterol i.e. (101% and 106%) and pyruvic acid increased significantly to a maximum value of 106% after 6 hrs of treatment at 40% LD50. Glycogen levels in the gastrocnemius muscle were found to decrease significantly (p-0.05) to 43% and 92% at LD50 after injection of purified Ropalidia marginata venom after 8 h and 80% at LD50 compared to control. Moreover, up to 71% and 81% were obtained at 10 hrs of treatment with the same dose. In the present study, the purified toxins significantly changed the levels of biomolecules in blood serum, indicating their wider effects on cellular physiology due to toxic effects and stress on the animal. These toxins can be good antigens and stimulate immune responses in experimental mice.

Research Progress on the Innate Immunity of Bactrocera dorsalis (Hendel) and the Regulation Mechanism of Parasitic Wasp Venom Protein

[Objectives]The use of natural enemies of living insects and their derivatives can effectively avoid the problems of pesticide residues,pest resistance,biodiversity decline,control effect weakening and so on.[Methods]Parasites inject various parasitic factors into hosts to inhibit the development of hosts,adjust the immunity of hosts,interfere with the growth and development of hosts,and reduce the nutrition metabolism of hosts,so as to ensure the growth and development of the offspring.Host pests can escape or conquer the parasitism of parasitic wasps through immune defense system in order to reproduce their own offspring.[Results]Under intense and strong selection pressure,in order to effectively ensure the success rate of parasitism,the adaptive diversity of parasitism strategies of parasitic wasps is finally caused.In the process of evolution and under the pressure of directional selection,the innate immunity and acquired immunity gradually evolve.[Conclusions]In-depth research on parasitic factors of parasitic wasps and their interaction with crop pests immunity and development can not only improve theoretical understanding of insect immunity and development biology,pest biological control and other disciplines,but also be expected to enable the application of some components of parasitic factors to agriculture,medicine and pharmacy.Bactrocera dorsalis is a destructive fruit and vegetable pest.This paper summarized the venom protein of B.dorsalis parasitoids and the immune interaction with hosts,in order to provide theoretical basis for biological control of plant pests by using parasitic natural enemies.

Faunal data and envenomation emergency first aid of cone snails (Conus spp.) in Qeshm Island, the Persian Gulf

Objective: To investigate the fauna of a highly venomous marine species group, the cone snails(Family Conidae), in the shores of Qeshm Island, of evaluating the possibility of envenomation in the area and summarize recommendations for emergency first aid.Methods: Shores surrounding Qeshm Island were surveyed to collect cone snails during cold(February and March) and warm(May and June) seasons of 2017. Collected snails were identified to the species level. Abundance and species richness were estimated in shores of different structures, including muddy and sandy-rocky shores. Also, the most updated medical literature was reviewed to summarize related emergency first aid.Results: Three cone snail species were recorded from southern sandy-rocky shores of the Island, in decreasing order of abundance, included crowned cone(Conus coronatus)(65%), feathered cone(Conus pennaceus)(28%), and frigid cone(Conus frigidus)(7%).Abundance of these species were significantly higher in cold season compared to the warm season(P < 0.05). No cone snails were recorded along the northern muddy shores of the Island.Conclusions: Envenomation can cause various symptoms ranging from minor local pain to systemic paralysis and death due to respiratory failure. We recommend an awareness programme for the seashore visiting public.

Determination of median effective dose(ED_(50)) of scorpion antivenom against scorpion envenomation using a newly developed formula

Background: About 50 species of scorpions cause fatal scorpionism worldwide.Most of these are members of the Buthidae family, and include, among others,Mesobuthus eupeus, Androctonus crassicauda, Leiurus abdullahbayrami, Leiurus quinquestriatus, Tityus pachyurus and Androctonus australis. Because high doses of scorpion venom and antivenom can cause death and hypersensitive reactions, there is a need to develop a formula that can be used to calculate both lethal and effective doses for scorpion venom and antivenom, respectively, thereby obviating the need for laboratory experiments.Methods: In view of this, a literature search was carried out with the aim of modifying the formula(LD_(50)=ED_(50)/3× W_a × 10^(-4))for calculation of the median lethal dose(LD_(50)) of scorpion venom and the ED_(50) of antivenom. The human equivalent dose(HED) formula was assessed for extrapolation of LD_(50) and ED_(50) from animals to human for comparison and relevance with the new formula.Results: The findings showed that the newly developed formula(LD_(50)= ED_(50)^(1/3)×W_a× 10^(-4)) yielded results that are very close to the reported values. Therefore, the newly developed and HED formulas can be used for calculation of LD_(50) and ED_(50) values for scorpion venom and antivenom, respectively.Conclusion: The new formula yielded better results than the HED formula, confirming its predictive validity, precision, and reliability, thereby obviating the need for rigorous experiments and justifying the principles of reduction, refinement, and replacement(3 Rs).

Anti-trypanosomal Activity of Bufonidae(Toad)Venom Crude Extract on Trypanosoma brucei brucei in Swiss Mice

Trypanosomiasis afflicts about 6~7 million people globally and to a large extent impedes livestock production in Africa.Naturally,trypanosomal parasites undergo genetic mutation and have developed resistance over a wide range of therapies.The utilization of animals and plants products has presented therapeutic potential for identifying novel anti-trypanosomal drugs.This study evaluated toad venom for anti-trypanosomal potency in-vivo in Swiss mice.Toads were collected from July to August 2019.The acute oral toxicity and biochemical characterization of the toad venom were determined.The experimental mice were administered various doses(130 mg/kg,173 mg/kg and 217 mg/kg)of the toad venom crude extract and 0.75 mg/mL of Diamizan Plus standard drug for the treatment of trypanosomiasis,once daily for 3 days.The in-vivo anti-trypanosomal activity was evaluated by a curative test,after infecting the mice with Trypanosoma brucei brucei.The pre-patent period was 72 hours before treatment commenced.The overall results showed that trypanosomal load was highest in the control group while the group treated with Diamizan drug had the least trypanosomal load.As such,the mean trypanosomal load in relation to treatments showed a very high significant difference(P<0.05).Also,the mean trypanosomal load in Swiss mice in relation to the highest dosage of toad venom versus Diamizan drug showed a very high significant difference(P<0.05).The mean change in relation to the haematological parameters across treatments groups varied significantly(P<0.05)with the exception of Hb which showed no significant difference(P>0.05)across treatment groups.The over 50%reduction in the trypanosomal load in the 130 mg/kg group in comparison with the control group brings to bare the anti-trypanosomal potency of the toad venom.The anti-trypanosomal activity demonstrated by the toad venom has provided basis for development of new therapeutic agents from different toad species.The study recommends further studies(both in-vivo and in-vitro)followed by the characterization of the active compounds present in the toad venom responsible for the anti-tyrpanosomal activity observed alongside the management and conservation of these species.

Therapeutic potential of snake venom in cancer therapy:current perspectives

Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer.Snake venom toxins coutributed significantly to the treatment of many medical conditions.There are many published studies describing and elucidating the anti-cancer potential of snake venom.Cancer therapy is one of the main areas for the use of protein peptides and enzymes originating from animals of different species.Some of these proteins or peptides and enzymes from snake venom when isolated and evaluated may bind specifically to cancer cell membranes,affecting the migration and proliferation of these cells.Some of substances found in the snake venom present a great potential as anti-tumor agent.In this review,we presented the main results of recent years of research involving the active compounds of snake venom that have anticancer activity.

Therapeutic Potential of Naja Naja Atra Venom in A Rat Model of Diabetic Nephropathy

Objective To study the protective effects of naja naja atra venom （NNAV） in a rat model of diabetic nephropathy （DN）. Methods The rat diabetes model was induced by intraperitoneal injection of streptozotocin （STZ）. Thirty-two model rats were randomly divided into one DN group （n=8） and three treatment groups （n=8 each） that received NNAV at doses of 30, 90, or 270 I^g/（ks.day） via oral gavage, another eight rats as normal controls. After 12 weeks, all rats were sacrificed and the changes in serum and urine biological index levels were determined by colorimetric assay. Microalbumin （mALB）, N-acetyl-13- glucosaminidase （NAG） and cystatin C （CysC） concentrations were measured by ELISA. Renal tissues were sliced for pathological and immunohistochemical observations. Results Comparied with the DN group, serum glucose was decreased by 31.04%, total cholesterol 21.96%, triglyceride 23.78%, serum creatinine 19.83%, blood urea nitrogen 31.28%, urinary protein excretion 45.42%, mALB 10.42%, NAG 20.65%, CysC 19.57%, whereas albumin increased by 5.55%, high-density lipoprotein-cholesterol 59.09%, creatinine clearance 19.05% in the treatment group by NNAV administration at dose of 90 μg/（kg-day）. NNAV also reduced the levels of malondialdehyde in serum （22.56%） and kidney tissue （9.79%）, and increased superoxide dismutase concentration in serum （15%） and decreased it in renal tissue （8.85%）. In addition, under light microscopy kidney structure was improved and glomerular hypertrophy decreased by 8.29%. As shown by immunohistochemistry, NNAV inhibited transforming growth factorl by 6.70% and nuclear actor-KB by 5.15%.

Applications of snake venoms in treatment of cancer

Snake venoms are folk medicines used since ages. The components of snake venoms have high specific affinity and actions on cells and cell components. Also snake venoms are largely cytotoxic to tumor cells than normal cells. In addition to these, they have several therapeutic actions that make them an attractive option in the management of cancer. The advent of modern technologies has greatly helped in extracting and identifying new components of therapeutic interests in short time. The article highlights the importance of snake venoms in the management of cancer, so as to motivate curious researchers to devote their skills in this fascinating area. This in turn may bring hope, smile and relief to several cancer patients in future.

Effects of cosmetics containing purified honeybee(Apis mellifera L.) venom on acne vulgaris

Acne vulgaris is a chronic dermatologic problem with multiple factors involved in its pathogenesis. Alternative solutions to acne treatment were instigated by antibiotic resistance despite of its extensive use. Purified bee venom （PBV） has been proposed as a promising candidate for that purpose. The present study was designed to confirm the antibacterial effect of PBV and access the efficacy of cosmetics containing PBV in subjects with acne vulgaris. METHODS： The skin bacterium Propionibacterium acnes was incubated with PBV at various concentrations and bacterial growth was evaluated using the colony forming unit （CFU） assay. The mechanism of PBV employed in killing P. acnes was examined by scanning electron microscopy （SEM） and transmission electron microscopy （TEM）. In addition, a total of 12 subjects were randomized in a double-blind, controlled trial to receive either cosmetics containing PBV or cosmetics without PBV for two weeks. Evaluations included lesion counts and skin microorganism. RESULTS： PBV exhibited antimicrobial activity in a concentration-dependent manner, reducing the number of P. acnes CFU by approximately 6 logs at a concentration of 0.5 mg. When PBV concentration was higher than 1.0 mg, no P. acnes colonies were spotted on an agar. TEM and SEM of untreated P. acnes illustrated the normal pleomorphic structure, whereas the PBV- treated bacterium lost the integrity of surface architecture. Significant difference （P=0.027） in the grading levels based on numbers of lesion counts for inflammatory and noninflammatory was observed in favour of the PBV group compared with the control group. In terms of average decrement of skin microorganism, subjects receiving cosmetics containing PBV experienced a significant 57.5% decrease of adenosine triphosphate levels, whereas participants receiving cosmetics without PBV experienced a nonsignificant decrease of 4.7%. CONCLUSION： These results show that the in vitro actions of antimicrobial activity of PBV were translated in vivo. Cosmetics containing PBV provided a certain degree of efficacy in terms of lesion counts and skin microorganism concentration compared with cosmetics without PBV in subjects with acne vulgaris. PBV may be a good candidate compound for developing therapeutic drua for the treatment of acne vulaaris.

Animal venom studies: Current benefits and future developments

Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, compositions of which depend on species producing venom. The most known and studied poisonous terrestrial animals are snakes, scorpions and spiders. Among marine animals, these are jellyfishes, anemones and cone snails. The toxic substances in the venom ofthese animals are mainly of protein and peptide origin. Recent studies have indicated that the single venom may contain up to several hundred different components producing diverse physiological effects. Bites or stings by certain poisonous species result in severe envenomations leading in some cases to death. This raises the problem of bite treatment. The most effective treatment so far is the application of antivenoms. To enhance the effectiveness of such treatments, the knowledge of venom composition is needed. On the other hand, venoms contain substances with unique biological properties, which can be used both in basic science and in clinical applications. The best example of toxin application in basic science is α-bungarotoxin the discovery of which made a big impact on the studies of nicotinic acetylcholine receptor. Today compositions of venom from many species have already been examined. Based on these data, one can conclude that venoms contain a large number of individual components belonging to a limited number of structural types. Often minor changes in the amino acid sequence give rise to new biological properties. Change in the living conditions of poisonous animals lead to alterations in the composition of venoms resulting in appearance of new toxins. At the same time introduction of new methods of proteomics and genomics lead to discoveries of new compounds, which may serve as research tools or as templates for the development of novel drugs. The application of these sensitive and comprehensive methods allows studying either of venoms available in tiny amounts or of low abundant components in already known venoms.

Identifying Intraspecific Variation in Venom Yield of Chinese Cobra(Naja atra) from Ten Populations in China's Mainland

Detailed information on venom yield is helpful in preparing antivenoms and treating snakebites, but such information is lacking for many species of venomous snakes. The Chinese cobra(Naja atra) is a large sized, venomous snake commonly found in southeastern China, where it causes a heavy burden of snakebites. To examine the effects of various factors(morphology, sex, age, season, and geographical origin) on the venom yield in this snake, we collected venom samples of 446 individuals(426 adults and 20 neonates) from 10 populations of N. atra over an eightyear period. We used two variables, lyophilized venom mass(venom yield) and solid content of venom(% solids), to quantify the venom yield. We used linear regression analysis to check if venom yield was related to morphological factors, one-way ANOVA and one-way ANCOVA to detect the sexual, ontogenetic, and geographic variation in venom yield, and repeated-measures ANOVA to examine seasonal shifts in venom yield. Our results indicate that venom yield of N. atra is positively related to the morphological traits examined, with male snakes expelling more venom than females. Venom yield in N. atra was age-related, with elder snakes always expelling more venom than younger ones. Geographic variation in venom yield was also observed, while seasonal variation was not. The solid content of venom was lower in males than in females, but this was not related to morphology, season, age, or geography. Our findings suggest that venom yield in N. atra is influenced by multiple factors, as well as by the interactions among these factors.

Investigation of the Biochemical and Histological Changes Induced by Zearalenone Mycotoxin on Liver in Male Mice and the Protective Role of Crude Venom Extracted from Jellyfish <i>Cassiopea Andromeda</i>

Zearalenone (ZEN) is a non steroidal estrogenic mycotoxin produced by Fusarium species of fungi which contaminate human foods and animal feeds worldwide. In this study hepatotoxicity of ZEN was evaluated in mice by oral adminis-tration of single and repeated doses of ZEN mycotoxin (2.7 mg/kg b.w.). The protective effect of crude venom extracted from jellyfish Cassiopea andromeda was also assessed. Mice were divided into four groups (N = 10). G1: receiving the toxin once and sacrificed 48 h later, G2: toxin administered twice for one week, G3: toxin administered twice a week for two weeks, G4: pretreated orally by a single dose of crude venom (1.78 mg/20g) 24 hours prior to administration of ZEN twice a week for two weeks. Each treated group had its corresponding control which received 1% DMSO sa-line.ZEN treatment significantly increased alanine aminotransferase (ALT), aspartateaminotrnsferase (AST) and alka-line phosphatase (ALP) activities after 48 hours and two weeks, while ALT was also significantly increased after one week. Tumor necrosis factoralpha (TNF-α) level was undetected in treated and control groups except the group treated with ZEN for one week. Alphafetoprotein (AFP) level was increased significantly only after two weeks. The activity of antioxidants was significantly increased in all groups. ZEN was also found to modify the serum proteins especially gamma-globulin which showed a significant decrease after 48 h and two weeks. Improvement in liver func-tion occurred in the group pretreated with the crude venom, and AFP and antioxidants returned to normal level, while TNF-α level was also undetected. Gamma globulin was significantly increased. The recovery observed in the group which was pretreated with crude venom may related to bradykinin content of this venom which exhibits a hepatoprotective effect. Histological changes in mouse liver coincided with biochemical changes. In conclusion, this study revealed that ZEN induced liver function and structural changes promising an approach for using a crude venom of jellyfish to enhance liver function.

Anti-arthritic effects of microneedling with bee venom gel

Objective:To combine with transdermal drug delivery using microneedle to simulate the bee venom therapy to evaluate the permeation of bee venom gel.Methods:In this study,the sodium urate and LPS were used on rats and mice to construct the model.Bee venom gelemicroneedle combination effect on the model is to determine the role of microneedle gel permeation by observing inflammation factors.Results:Compared with the model group,the bee venom gelemicroneedle combination group can reduce the level of serum nitric oxide of the acute gouty inflammation model caused by sodium urate,and on LPS induced mouse model of acute inflammation effect and the micro.Conclusions:Bee venom can significantly suppress the occurrence of gouty arthritis inflammation in rats and mice LPS inflammatory reaction.Choose the 750 mm microneedle with 10N force on skin about 3 minutes,bee venom can play the optimal role,and the anti-inflammatory effect is obvious.Microneedles can promote the percutaneous absorption of the active macromolecules bee venom gel.

Protective Effect of Ozone against Hemiscorpius lepturus Envenomation in Mice

Objective Scorpion （Hemiscorpius lepturus） stings are a public health concern in Iran, particularly in south and southwestern regions of Iran. The gold standard for the treatment of a scorpion sting is anti-venom therapy. However, immunotherapy can have serious side effects, such as anaphylactic shock （which can sometimes even lead to death）. The aim of the current study was to demonstrate the protective effect of ozone against toxicity induced by Hemiscorpius lepturus （H. lepturus） venom in mice. Methods Eight hours after the injection of ozone to the experimental design groups, the male mice were decapitated and mitochondria were isolated from five different tissues （liver, kidney, heart, brain, and spinal cord） using differential ultracentrifugation. Then, assessment of mitochondrial parameters including mitochondrial reactive oxidative species （ROS） production, mitochondrial membrane potential （MMP）, ATP level, and the release of cytochrome c from the mitochondria was performed. Results Our results showed that H. lepturus venom-induced oxidative stress is related to ROS production and MMP collapse, which is correlated with cytochrome c release and ATP depletion, indicating the predisposition to the cell death signaling. Conclusion In general, ozone therapy in moderate dose can be considered as clinically effective for the treatment of H. lepturus sting as a protective and antioxidant agent.

Interventional effect of scorpion venom from Buthus martensii Karsch in Liaoning on somatic pain

BACKGROUND： Scorpion venom from Buthus martensii Karsch is a kind of protein toxin secreted by scorpion tail. According to records of Pen-ts ＇ao Kan-mu, the dried scorpion＇s body and tail are used as medicine, which mainly treating rheumatism numbness, pain and convulsion. Some researches consider that scorpion toxin is the main pharmacological active component of the dried scorpion, and it has 4 times stronger analgesic effect on somatic pain than morphine. OBJECTIVE： To observe the interventional effect of scorpion venom of Buthus martensii Karsch analgesic active peptide on somatic pain. DESIGN： A randomized and controlled trial SETTING： Department of Physiology, Shenyang Medical College MATERIALS： Totally 80 Wistar rats （provided by Animal Center of Shenyang Medical College）, male and female in half, aged 3 to 4 months, weighed 250 to 350 g, were used in this trial. They were randomly divided into 4 groups： experimental group, control group, morphine group and naloxone group, with 20 in each group. Analgesia active peptide from buthus martensii karsch venom （provided by Biochemical Department of Shenyang Pharmaceutical University, 1 mL/dosage）, morphine （produced by Shanghai First Pharmaceutical Manufacturing Plant）, naloxone （opium acceptor inhibitor, American Sigma Corporation）, AT- AC-350 data-processing machine （Nihon Kohden Corporation）, X-Y recording instrument （Nihon Kohden Corporation）. METHODS： The experiment was conducted in the Department of Physiology, Shenyang Medical College from July 2003 to July 2005. ① After all the animals were anesthetized, common peroneal nerve is dissected and ligated at middle part. Posterior nucleus group of thalamus （PO） and the tail nuclear were oriented according to G. Paxino rat brain three-dimensional orientation atlas, Glass micro electrode was inserted into PO as guiding electrode, connected with ATAC-350 data-processing machine and X-Y recording instrument, to record the unit evoked potential of PO, taking the evoked potential discharge of the common peroneal nerve of PO as the somatic pain index.② Single square-wave stimulation of intensity 17-19 volt, wave wide 0.2 ms, time delay 20 ms was exerted on common peroneal nerve. The time interval was 5 minutes. X-Y recording instrument was used to draw the graph. 0,002 mg scorpion venom analgesic active peptide was injected into the rats of the experimental group; 0.002 mg normal saline was injected into the rats of the control group through caudate nucleus; 0.002 mg morphine was injected into the rats of morphine group through caudate nucleus; 1.0 mg/kg naloxone was intraperitoneally into the rats of naloxone group, then 0.002 mg scorpion venom was injected into the rats of control group through caudate nucleus.Changes of evoked potential of PO of 3 groups were observed. ③After experiment, 1 μA direct current was given to the guiding electrode and micro electrode , and it lasted for 5 minutes. Pontamine sky blue was used to label the peak of electrode by electrophoresis. Brain tissue was soaked in formalin for 1 week then sliced into 1.0 to 1.5 mm sections. Electrode was orientated according to blue spots. Compared with G . Parino rat brain three-dimensional orientation atlas, we confirmed if the electrode orientation is consistent with PO orientation of G. Parino rat brain three-dimensional orientation atlas. MAIN OUTCOME MEASURES ： Changes of the evoked potential of PO in each group RESULTS： Totally 80 Wistar rats were enrolled in this experiment. Four rats in the experimental group and two in the morphine group died of overdose of anesthesia, and finally 74 rats entered the stage of result analysis. The inhibitory action time of evoked potential of PO has no statistical difference in between experiment group and morphine group （P 〉 0.05）. The whole inhibitory action time, timeof initiate recovery and time of complete recovery of PO of experiment group were longer than those in the morphine group [（45±0.7）, （50±9.2）, （65±8.1）：（35±7.8）. （40±8.9）. （50±7.6） min .P 〈 0.05].The change of evoked potential of PO was not obviously in the control group and naloxone group （P 〉 0.05）, and the above-mentioned 4 indexes were nearly 0. CONCLUSION： Scorpion venom possesses obviously inhibitory effect on somatic pain, and its inhibitory effect is stronger than that of the same dosage and concentration of morphine. Scorpion venom exerts analgesic effect on somatic pain through opium acceptor.

Snake Venom Antithrombus Ezyme: Column Chomatography Sepration

The preliminary results of our research with column chromatography inbrief is presented to separate and purify simultaneously various kinds offractions with biochemical and pharmaceutical activities from a kinds ofsnake venom and to make the proceeding either simplicity or economy. 2g of dry agkistrodon halys pallas of Jiang Ze area dissolved with

Antithrombotic effect of a novel tissue plasminogen activator from the venom of Gloydius brevicaudus viper

OBJECTIVE To investigate the thrombolytic and antiplatelet effects of a novel plasminogen activator from the venom of Gloydius brevicaudus viper(GBV-PA)in vitro and in vivo.METHODS Thrombolytic experiments were performed in rabbit models of ear vein thrombosis and carotid artery thrombosis,and in dog model of acute cerebral infarction.Inhibition of thrombus formation was evaluated in rat inferior vena cava thrombosis model and ferric chloride-induced arterial thrombosis.In vitro,we assayed the antithrombotic effect of GBV-PA on rabbit blood clots,euglobulin lysis time(ELT)of rabbit plasma,and on ADP-induced platelet aggregation.RESULTS GBV-PA intravenous administ ration significantly reduced vascular recanalization times of rabbit ear veins thrombosis and thrombus weight of rabbit carotid artery thrombosis.The arterial recanalization rates were dose-and time-dependently improved after administration of GBV-PA in canine acute cerebral infarction model.Thrombus length and weight was significantly reduced by GBV-PA both in rat inferior vena cava and ferric chloride-induced arterial thrombosis models.Thrombus formation of blood of rabbits they were administrated with GBV-PA was also inhibited.GBV-PA radically reduced plasma ELT of rabbit′s blood clots.ADP-induced platelet aggregation was inhibited by GBV-PA in a dose-dependent manner with a half-maximal inhibitory concentration of 19.9μg·mL-1.CONCLUSION This study demonstrates that GBV-PA is a thrombolytic and antiplatelet agent.It has significant antithrombotic effects on various in vitro and in vivo experimental models of thrombosis.The mechanisms that underline its antithrombotic effects were related to GBV-PA′s capabilities of increasing fibrinolytic activities and inhibition of platelet aggregation.

Inhibitory effects of microinjection of morphine into thalamic nucleus submedius on ipsilateral paw bee venom-induced inflammatory pain in the rat

Objective To examine whether microinjection of morphine into the rat thalamic nucleus submedius (Sm) could depress the bee venom (BV)-induced nociceptive behaviours. Methods In inflammatory pain model induced by BV subcutaneous injection into rat unilateral hind paw,the inhibitory effects of morphine microinjection into thalamic nucleus submedius (Sm) on the spontaneous nociceptive behavior,heat hyperalgesia and tactile allodynia,and the influence of naloxone on the morphine effects were observed in the rat. Results A single dose of morphine (5.0 μg,0.5 μL) applied into the Sm ipsilateral to the BV injected paw significantly depressed the spontaneous paw flinching response. Morphine also significantly increased the heat paw withdrawal latencies in the bilateral hind paw and the tactile paw withdrawal threshold in the ipsilateral hind paw 2 hours after BV injection. All these depressive effects could be effectively antagonized by pre-treatment with the opioid receptor antagonist naloxone (1.0 μg,0.5 μL) in the Sm 5min prior to morphine administration. Naloxone alone injected to the Sm had no effect on the BV-induced nociceptive behavior. Conclusion These results suggest that Sm is involved in opioid receptor-mediated anti-nociception in the rat with the BV-induced inflammatory pain. Together with results from previous studies,it is likely that this effect is produced by activation of the Sm-ventrolateral orbital cortex-periaqueductal gray pathway,leading to activation of the brainstem descending inhibitory system and depression of the nociceptive inputs at the spinal cord level.

EFFECT OF BUNGARUS MULTICINCTUS CRUDE VENOM AND ITS COMPONENTS ON TUMOR CELLS

Objective: To confirm whetherBungarus multicinctus crude venom induces the apoptosis of K562 tumor cells and to find out the components inducing apoptosis of K562 cells from the crude venom. Methods: the crude venom separated and purified by cation exchange chromatography, and the effect of venoms on K562 was studied by MTT method and flow cytometry. Results: The crude venom began to kill K562 cells at than 8×l03ng/ml (the survival rate was 82.5%) concentration and the effect was more significant in 24 h when administrating 8×l05ng/ml (the survival rate was 29.4%) crude venom. Apoptotic bodies were observed in the K562 tumor cells by fluorescent microscopy after administration of 5 μg/ml cycloheximide (CHX) or the peak VI solution at about 8×105 ng/ml. The same results were detected by the flow cytometry. A sub-Gi peak appeared after administration of CHX or the sixth peak solution. Conclusion: The authors found that the venom can kill K562 tumor cells in time- and dose-dependent manner. However, the killing effect of the venom is not apoptosis. What’s more, the peak VI solution, a component of the crude venom can induce the apoptosis of K562 tumor cells.