Oral Immunization for Anti-snake Venom Production in Equine Animals

The immunization process of current commercial manufacturing of anti-snake venom (ASV), uses injections of bentonite, complete Freund’s adjuvant, or incomplete Freund’s adjuvant, mixed with low doses of the snake venom in horses (but rarely in other large mammals), which frequently cause serious adverse effects in host animals. At the site of injection, horses may develop painful swelling, granuloma, abscess, scar, or systemic neurological and hematological defects, low antibody response, or death due to anaphylactic shock. We sought to investigate a novel alternate immunization strategy with oral administration of snake venom with adjuvants. We utilized M5904 mineral oil emulsion as an adjuvant that was mixed with sub-lethal doses (LD) of the snake venoms. Our preliminary experiments were initiated in March 2011 and the present data culminated in March 2018. In our initial experiments which were carried out in inbred mice, the LD100 was 10.36 ug/25 grams of mice for Naja. oxins and 10.0 ug/25 gram of Naja. karachians. We extrapolated the sub-LD dose to horses by cutting the LD100 in mice to 20%. This dose did not cause any apparent pathology in horses and therefore, we adopted that dose for the equine.

Evaluation of Chinese cobra venoms in preventing the kidney from ischemia/reperfusion injury / 中华肾脏病杂志

Objective To investigate the renal protection of Chinese cobra venoms (CCV) and its mechanism in renal ischemia/reperfusion (I/R). Methods Thirty-two rats were divided into four groups. 0.1% CCV was separately infused into abdominal cavity at 0.5 h, 24 h before reperfusion in group Ⅰ and Ⅱ . Group Ⅲ suffered from kidney I/R was served as pathological control. Group Ⅳ was sham operation group. BUN and Scr were measured before ischemia and 24 h after reperfusion. Complement C3 was observed at 0, 0.5, 2, 24 h after reperfusion. The kidney samples were examined by HE stain under light microscopy. Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP-biotin in situ nick-end labeling(TUNEL). Results Significant histological damage, apoptosis of tubular cell and impaired renal function were found in group Ⅰ and Ⅲ.The above indexes decreased to a less extend in group Ⅱ (P

Inhibition of proliferation and apoptosis in HL60 cells induced by cobra venom serum / 中国药理学通报

AIM: To explore the effects and mechanism of cobra venom serum on the proliferation in HL60 cells. METHODS: Established the HL60 cells as a target to study the growth feature by the action of cobra venom serum. The agarose gel electrophoresis and flow cytometry analysis were used to demonstrate apoptosis. RESULTS: Compared with the control group, the cells were inhibited significantly by the action of cobra venom serum. A characteristic DNA "ladder" was detected by using agarose gel electrophoresis. By flow cytometry analysis, it was proved that most apoptosis of HL60 cells occurred when cultured with cobra venom serum. CONCLUSION: Cobra venom serum inhibited the HL60 cells in vitro, which was related to apoptosis. This may introduce a new way to the treatment of leukemia.

Effect of naja naja atra venom on plasmic GSH-PX and catalase of human nasopharyngeal carcinoma bearing nude mice / 中国病理生理杂志

AIM: To investigate the changes of plasma glutathione peroxidase (GSH-PX) and catalase (CAT) activities in nude mice (NM) bearing human nasopharyngeal carcinoma (NPC) and observe the effect of naja naja atra venom (NNAV) on them. METHODS: Plasma GSH-PX and CAT activities in human NPC bearing NM treated ( i.p. ) by low, middle or high concentration NNAV solution (1 mg/L, 5 mg/L, 10 mg/L) were determined by colorimetry. RESULTS: Plasma CAT activity (16 450 U/L) in NM bearing tumor group decreased significantly in comparison with the control group (20 680 U/L)(P0.05). Treated by low, middle or high concentration NNAV solution, CAT activities of three NM bearing tumor groups (20 570 U/L, 23 090 U/L, 21 280 U/L ) were higher than that of the NM bearing tumor group without NNAV treatment (16 450 U/L) (P0.05). GSH-PX activities of the three groups (especially high concentration group) were higher than that of the group without NNAV treatment (P

Pharmacokinetics and distribution of fraction Ⅲ isolated from Naja naja atra venom / 中国病理生理杂志

AIM: To investigate the distribution in mice and pharmacokinetics in rabbits of fraction Ⅲ isolated from Naja naja atra venom. METHODS: Fraction Ⅲ was labelled with [~(125)Ⅰ] by chloramine-T method. The drug concentration in blood was determined by a radionuclide tracing kinetic methods. The distribution of [~(125)Ⅰ]-fraction Ⅲ in mice was determined based on the ratio of the relative incorporation of radioactivity in tissues to that in blood. RESULTS: In two and four hours after intravenous injection of fraction Ⅲ in mice, the organs in which the ratio of the radioactivity incorporation was bigger than 1 were liver, kidney, lung, heart and muscle, whth the maximun in kidney. After intravenous injection of fraction Ⅲ, with dosages of 75, 150 and 300 ?g/kg, respectively, the T_(1/2)?, T_(1/2)? and T_(1/2)? were 39.6-42.5 min, 16.8-17.3 h and 21.7-22.1 h, respectively. There was no significant difference between the different dosages. CONCLUSION: Fraction Ⅲ was mostly found in kidney, followed by liver and lung after intravenous administration in mice. The pharmacokinetics is in accordance with the feature of three atrioventricular modle. The AUC is in direct proportion to the dosage. It suggests that the distribution and clearance of the drug is a grade 1 linear kinetic process. [

The effect of Chinese Cobra venom on hyperacute rejection of guinea pig cardiac xenografts / 中华器官移植杂志

In an in vivo guinea pig-to-rat cardiac xenotransplantation model,the effect of complement depletion by using Chinese Cobra venom(CCV)on hyperacute rejection(HAR) was evaluated.A single low dose of 0.25～0.5mg/kg CCV given i.P.to SD significantly reduced hemolytic C activity for up to 24 hours.Rats receiving GP cardiac xenografts with CCV therapy min in control rat,P<0.01).Combination therapy using CCV,splenectomy and prostaglandin E1 induced 20~40 hours graft survival.Histologic analysis of GP cardiac xenograft taken from CCV-treated rats revealed monocyte infiltration,extensive hemorrhage and areas of myocardial necrosis 12～40 hours after transplantation.The histologic findings suggested that the monocyte may be involved in delayed xenograft rejection.Our study showed that the complement system plays an important mediating role in the hyperacute rejection in guinea pigs.

Inhibition of proliferation and apoptosis in HL60 cells induced by cobra venom serum / 中国药理学通报

AIM To explore the effects and mechanism of cobra venom serum on the proliferation in HL60 cells. METHODS Established the HL60 cells as a target to study the growth feature by the action of cobra venom serum.The agarose gel electrophoresis and flow cytometry analysis were used to demonstrate apoptosis. RESULTS Compared with the control group, the cells were inhibited significantly by the action of cobra venom serum.A characteristic DNA "ladder" was detected by using agarose gel electrophoresis. By flow cytometry analysis,it was proved that most apoptosis of HL60 cells occurred when cultured with cobra venom serum. CONCLUSION Cobra venom serum inhibited the HL60 cells in vitro , which was related to apoptosis. This may introduce a new way to the treatment of leukemia.

Effect of fraction F of naja naja atra venom on protein tyrosine phosphorylation in platelet activation / 中国病理生理杂志

AIM: To observe the mechanism of intracellu la r signal transduction that fraction F of naja naja atra venom inhibits plate let aggregation. METHODS: Tests were divided into six groups: (1) blank group; (2 ) control group and (3)-(6) ADP plus fraction F group (doses of fraction F were 100, 30, 10, 3 mg/L, respectively). Protein tyrosine phosphorylation in platelet s was assayed by Western blotting and platelet aggregation was assayed by nephel omete r. RESULTS: Fraction F significantly inhibited molecular masses (MW ) 76, 66 and 37.5 kD protein tyrosine phosphorylation in platelet that induced by ADP in a dose-dependent manner, in which 30 and 100 mg/L dose group showed ob viously different effects when compared to control group (P