Cobra Research Articles

Extract of Celosia leptostachya Leaves Inhibits Cobra Venom Toxins

Background: Celosia leptostachya belongs to Amaranthaceae plant family. Its leaves are used traditionally in the treatment of conditions, such as convulsion, eye infection and most notably to cure snakebites. This study investigated the inhibiting effect of the extract of C. leptostachya leaves against cobra snake venom in mice. Methods: We used 36 albino mice of mixed gender, weighing 20-25 g. They were divided into six groups of six rats each. Each rat was pre-treated with 0.4 mg/kg of cobra snake venom, and was subsequently given a graded dose of zero, 50, 100, 150, 200, or 250 mg/kg of the ethanol extract of C. leptostachya leaves. The animals were monitored for the survival rate. Various inhibition assays were performed to estimate the activities of acetyl cholinesterase, protease and adenosine triphosphatase of cobra venom, in the presence of 100-300 µg of the plant extract. Results: The extract inhibited the effects of cobra venom significantly after the intraperitoneal injection of the venom and extract at 20 minutes intervals. The results demonstrated that 100% of the mice survived if they received 100-250 mg/kg of the extract while only 83.3% survived with the extract at 50 mg/kg. The extract inhibited the venom’s acetyl cholinesterase, protease and adenosine triphosphatase. The inhibition occurred at higher percentages if the extract was given at 300 mg/kg. Conclusion: The plant extract significantly inhibited the snake venom, and its acetyl cholinesterase, protease and adenosine triphosphatase that mediated the venom’s toxicity.

Identification of Potential Insulinotropic Cytotoxins from Indian Cobra Snake Venom Using High-Resolution Mass Spectrometry and Analyzing Their Possible Interactions with Potassium Channel Receptors by In Silico Studies.

Snake venoms are a potential source of bioactive peptides, which have multiple therapeutic properties in treating diseases such as diabetes, cancer, and neurological disorders. Among bioactive peptides, cytotoxins (CTXs) and neurotoxins are low molecular weight proteins belonging to the three-finger-fold toxins (3FTxs) family composed of two β sheets that are stabilized by four to five conserved disulfide bonds containing 58-72 amino acid residues. These are highly abundant in snake venom and are predicted to have insulinotropic activities. In this study, the CTXs were purified from Indian cobra snake venom using preparative HPLC and characterized using high-resolution mass spectrometry (HRMS) TOF-MS/MS. Further SDS-PAGE analysis confirmed the presence of low molecular weight cytotoxic proteins. The CTXs in fractions A and B exhibited dose-dependent insulinotropic activity from 0.001 to 10µM using rat pancreatic beta-cell lines (RIN-5F) in the ELISA. Nateglinide and repaglinide are synthetic small-molecule drugs that control sugar levels in the blood in type 2 diabetes, which were used as a positive control in ELISA. Concluded that purified CTXs have insulinotropic activity, and there is a scope to use these proteins as small molecules to stimulate insulinotropic activities. At this stage, the focus is on the efficiency of the cytotoxins to induce insulin. Additional work is ongoing on animal models to see the extent of the beneficial effects and efficiency to cure diabetes using streptozotocin-induced models.

Selective sensory nerve blocks for effective pain management in the emergency department for a term pregnant cobra snake envenomation patient.

Sir, Snake bites with envenomation are a rare life-threatening emergency during pregnancy.[1] We report a case of a young full-term parturient who reported intense localized pain at the cobra (Naza Naza) bite site which was managed successfully by selective sensory nerve blocks. She subsequently underwent a caesarean section under spinal anaesthesia and had an uneventful post-partum course. A 26-year-old eight month pregnant patient presented to the emergency department (ED) post-cobra bite. The patient was taken to a local hospital within 30 min of the event. The bite mark was present on the right foot near the 4th toe [Figure 1]. There was minimal localized swelling but intense pain in the bite area. She had an episode of vomiting 45 min post-snake bite (suggesting the onset of systemic symptoms) and was administered 10 vials of anti-snake venom and referred to our tertiary care set-up.Figure 1: Distribution of superficial peroneal nerve (a); Probe placement for USG-guided block (b); USG image showing the superficial peroneal nerve (c); Snake bite mark on foot of the patient (d)When she presented to our ED 3h post-bite, the swelling had increased considerably and 10 more vials of anti-snake venom were infused. The investigations revealed leucocytosis with mild thrombocytopenia and anaemia. Local site pain was unbearable even after intravenous paracetamol and diclofenac. A superficial peroneal nerve and sural nerve blocks to cover the dorsolateral aspect of the foot was planned. The nerves were localized using a linear transducer (8–13 MHz) and a 3.5 ml of 0.75% ropivacaine was deposited. [Figures 1 and 2] Within 5 mins, the numeric rating scale (NRS) fall to 2 from the initial score of 10. At 10h, the patient reported an NRS score of 6, and the same blocks were repeated and effective pain relief was reported. The patient underwent a caesarean section under spinal anaesthesia at 18h post-admission given foetal distress. The baby was kept on nasal continuous positive airway pressure for 18h in view of respiratory distress and both of them were discharged in stable condition on the 3rd day of admission.Figure 2: Distribution of sural nerve (a); Probe placement for USG-guided block (b); USG image showing the sural nerve (c)Snake bites are rare in pregnancy but maternal mortality and foetal loss remain high.[1] An early presentation and rapidity of treatment with anti-snake venom probably led to a good outcome in this case. Acute localized moderate-to-severe pain is often documented as the first sign of a venomous snake bite (VSB).[2,3] The presynaptic and postsynaptic neurotoxins may directly interact with the nerve endings or indirectly cause severe pain secondary to ischemia due to local oedema.[1] Antivenom treatment fails to alleviate the local pain which may last for 48–72 h.[3] Weak opioids such as tramadol or paracetamol often provide inadequate analgesia.[4] Systemic opioids and non-steroidal anti-inflammatory drugs may be harmful to the foetus in term pregnancy. Furthermore, opioids can increase the risk of respiratory depression in neurotoxic envenomation cases as seen in cobra bite.[4] Untreated pain can have adverse consequences on foeto-maternal circulation.[5] In our case, the patient had intense pain with an NRS of 10 despite analgesics and responded well to nerve blocks. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

The Target Selects the Toxin: Specific Amino Acids in Snake-Prey Nicotinic Acetylcholine Receptors That Are Selectively Bound by King Cobra Venoms.

Snake venom is an adaptive ecological trait that has evolved primarily as a form of prey subjugation. Thus, the selection pressure for toxin diversification is exerted by the prey’s physiological targets, with this pressure being particularly acute for specialist feeders, such as the King Cobra species, all of which are snake-prey specialists. However, while extensive research has been undertaken to elucidate key amino acids that guide toxin structure–activity relationships, reciprocal investigations into the specific sites guiding prey-lineage selective effects have been lacking. This has largely been due to the lack of assay systems amenable to systematic amino acid replacements of targeted proteins in the prey’s physiological pathways. To fill this knowledge gap, we used a recently described approach based upon mimotope peptides corresponding to the orthosteric site of nicotinic acetylcholine receptor alpha-1 subunits, a major binding site for snake venom neurotoxins that cause flaccid paralysis. We investigated the venoms of four different types of King Cobra (Cambodian, Javan, Malaysian, and Thai). This approach allowed for the determination of the key amino acid positions in King Cobra snake prey that are selectively bound by the toxins, whereby replacing these amino acids in the snake-prey orthosteric site with those from lizards or rats resulted in a significantly lower level of binding by the venoms, while conversely replacing the lizard or rat amino acids with those from the snake at that position increased the binding. By doing such, we identified three negatively charged amino acids in the snake orthosteric site that are strongly bound by the positively charged neurotoxic three-finger toxins found in King Cobra venom. This study, thus, sheds light on the selection pressures exerted by a specialist prey item for the evolution of lineage-selective toxins.

In vitro discovery of a human monoclonal antibody that neutralizes lethality of cobra snake venom

ABSTRACT The monocled cobra (Naja kaouthia) is among the most feared snakes in Southeast Asia due to its toxicity, which is predominantly derived from long-chain α-neurotoxins. The only specific treatment for snakebite envenoming is antivenom based on animal-derived polyclonal antibodies. Despite the lifesaving importance of these medicines, major limitations in safety, supply consistency, and efficacy create a need for improved treatments. Here, we describe the discovery and subsequent optimization of a recombinant human monoclonal immunoglobulin G antibody against α-cobratoxin using phage display technology. Affinity maturation by light chain-shuffling resulted in a significant increase in in vitro neutralization potency and in vivo efficacy. The optimized antibody prevented lethality when incubated with N. kaouthia whole venom prior to intravenous injection. This study is the first to demonstrate neutralization of whole snake venom by a single recombinant monoclonal antibody, thus providing a tantalizing prospect of bringing recombinant antivenoms based on human monoclonal or oligoclonal antibodies to the clinic.

Induction of Apoptosis in Glioblastoma Cell Line (U87-MG) by Caspian Cobra (Naja naja oxiana) Snake Venom

Induction of Apoptosis in Glioblastoma Cell Line (U87-MG) by Caspian Cobra (Naja naja oxiana) Snake Venom

Development of an Inhibition Enzyme-Linked Immunosorbent Assay (ELISA) Prototype for Detecting Cytotoxic Three-Finger Toxins (3FTxs) in African Spitting Cobra Venoms.

The administration of toxin-specific therapy in snake envenoming is predicated on improved diagnostic techniques capable of detecting specific venom toxins. Various serological tests have been used in detecting snakebite envenoming. Comparatively, enzyme-linked immunosorbent assay (ELISA) has been shown to offer a wider practical application. We report an inhibition ELISA for detecting three-finger toxin (3FTx) proteins in venoms of African spitting cobras. The optimized assay detected 3FTxs in N. ashei (including other Naja sp.) venoms, spiked samples, and venom-challenged mice samples. In venoms of Naja sp., the assay showed inhibition, implying the detection of 3FTxs, but showed little or no inhibition in non-Naja sp. In mice-spiked samples, one-way ANOVA results showed that the observed inhibition was not statistically significant between spiked samples and negative control (p-value = 0.164). Similarly, the observed differences in inhibition between venom-challenged and negative control samples were not statistically significant (p-value = 0.9109). At an LOD of 0.01 µg/mL, the assay was able to confirm the presence of 3FTxs in the samples. Our results show a proof of concept for the use of an inhibition ELISA model as a tool for detecting 3FTxs in the venoms of African spitting cobra snakes.

Evaluation of Anti-Cancer Effects of Caspian Cobra (Naja naja oxiana) Snake Venom in Comparison with Doxorubicin in HeLa Cancer Cell Line and Normal HFF Fibroblast

Evaluation of Anti-Cancer Effects of Caspian Cobra (Naja naja oxiana) Snake Venom in Comparison with Doxorubicin in HeLa Cancer Cell Line and Normal HFF Fibroblast

A rare case of Panophthalmitis due to cobra bite.

Ocular manifestations of snake bite are rare, ranging from direct injury to the eye from snake venom or indirect injury due to antivenom. We report a rare case of cobra bite causing panophthalmitis due to indirect injury as a result of snake venom toxin related tissue necrosis and susceptibility to secondary infections. Observational case report. External photographs, slit lamp photos, ultrasonography of the eye and histopathology of the eviscerated eye were used to characterize and describe the clinical findings. Thirty-nine-years-old male farmer presented with history of cobra snake bite on his right index finger and developed right eye sudden onset pain and redness 3 days later. On examination, features were suggestive of panophthalmitis and the eye had to be eviscerated with scleral excision. It is important for ophthalmologist to be aware of such grave consequences of snake bite to be prepared for the emergency management of such cases.

Development of a Broad-Spectrum Antiserum against Cobra Venoms Using Recombinant Three-Finger Toxins.

Three-finger toxins (3FTXs) are the most clinically relevant components in cobra (genus Naja) venoms. Administration of the antivenom is the recommended treatment for the snakebite envenomings, while the efficacy to cross-neutralize the different cobra species is typically limited, which is presumably due to intra-specific variation of the 3FTXs composition in cobra venoms. Targeting the clinically relevant venom components has been considered as an important factor for novel antivenom design. Here, we used the recombinant type of long-chain α-neurotoxins (P01391), short-chain α-neurotoxins (P60770), and cardiotoxin A3 (P60301) to generate a new immunogen formulation and investigated the potency of the resulting antiserum against the venom lethality of three medially important cobras in Asia, including the Thai monocled cobra (Naja kaouthia), the Taiwan cobra (Naja atra), and the Thai spitting cobra (Naja Siamensis) snake species. With the fusion of protein disulfide isomerase and the low-temperature settings, the correct disulfide bonds were built on these recombinant 3FTXs (r3FTXs), which were confirmed by the circular dichroism spectra and tandem mass spectrometry. Immunization with r3FTX was able to induce the specific antibody response to the native 3FTXs in cobra venoms. Furthermore, the horse and rabbit antiserum raised by the r3FTX mixture is able to neutralize the venom lethality of the selected three medically important cobras. Thus, the study demonstrated that the r3FTXs are potential immunogens in the development of novel antivenom with broad neutralization activity for the therapeutic treatment of victims involving cobra snakes in countries.

Assessing Anti-malaria Effect of Naja Naja Oxiana Snake Venom by Real-time Polymerase Chain Reaction Method

Objective: Malaria is one of the most important parasitic diseases and one of the important health issues especially in tropical and subtropical countries. The importance of this disease is due to its high prevalence and mortality, as well as drug resistance and side effects of common drugs used for its treatment. Snake venom is a complex mixture of active pharmaceutical ingredients. The present study aims to investigate the anti-Plasmodium falciparum activity of the purified fractions isolated from the venom of Iranian cobra snake (Naja Naja Oxiana) by real-time Polymerase Chain Reaction (PCR) method. The importance of this disease is due to its high prevalence, significant mortality, as well as drug resistance and, side effects of current drugs in treatment. Venom is a complex mixture of active pharmaceutical ingredients. The purpose of this study was to investigate the anti-Plasmodium falciparum activity of the purified fraction of Iranian cobra snake venom by Real -time PCR. Methods: After preparation and purification of lyophilized venom for determining the parasitic load, different fractions obtained from the venom of Naja Naja Oxiana put in different plates adjacent to Plasmodium falciparum (3D7) strain in the ring stage. The degree of parasitemia was determined by real-time PCR. Finally, the effective fraction with anti-malaria properties was identified. Results: The active fraction with a half maximal inhibitory concentration of 0.026 μg/mL was the most effective fraction on Plasmodium falciparum in vitro (P<0.001). Conclusion: The active fraction of Naja Naja Oxiana venom at the mentioned concentration has anti-malaria effect. This results can motivate the continuation of further research in this field.

Experimental Evaluation of Mouse Hind Paw Edema Induced by Iranian Naja oxiana Venom.

Iranian Naja oxiana (the Elapidae family) known as cobra snake inhabits in the northwestern part of Iran. This study aimed to evaluate the edematogenic potency of the crude venom with intraplantar injection into mice. Additionally, the inhibitory effects of three different drugs (i.e., promethazine, dexamethasone, and piroxicam) on paw edema were examined. Moreover, the gelatinase activity of this venom was assessed using the zymography method. Paw edema was induced by the intraplantar injection of different concentrations of the venom (0.5-5 μg dissolved in 50 μl of normal saline) into the mice (six in each group). It was estimated through the measurement of the increase in the paw thickness (%) with a digital caliper. The paws were pretreated and the rate of changes was measured after the venom injection. Pathological findings in the treated paws were evaluated with hematoxylin and eosin staining. Paw thickness reached its maximum amount within 5 min and resolved after 1 h. This venom had no gelatinase activity using the zymography method ruling out its role in edema. It caused non-hemorrhagic diffuse edema with the infiltration of inflammatory cells (i.e., leukocytes and lymphocytes) in the dermis. Intraperitoneal pretreatment with drugs significantly inhibited the venom-induced (1 μg/paw) edema; however, all the mice died unexpectedly a day after piroxicam injection. This in vitro and in vivo preliminary study demonstrated for the first time that N. oxiana venom-induced non-hemorrhagic edema in a short time. Dexamethasone (phospholipase A2 inhibitor; 1 mg/kg) and promethazine (H1 inhibitor; 5 mg/kg) decreased the venom-induced edema (p <0.001). It is suggested to carry out further studies to identify different mediators in venom-induced edema formation.

Spitting cobras’ venom evolved to inflict pain

Spitting cobras’ venom evolved to inflict pain

Immunological properties of the chicken egg yolk (IgY) antibodies against Vietnamese cobra Naja Naja venom

Venomous snake bite is common poisonous accident and important medical problem around the world. The snake anti-venom is only type-specific protection to each venom type that was used to immunize. In this study, the chicken egg yolk (IgY) antibodies against the Vietnamese cobra Naja Naja venom was developed and evaluated in in-vitro (ELISA and SDS-PAGE) and in-vivo (hen and mice immunization). In particularly, the LD50 of the Vietnamese cobra Naja Naja venom was determined at 1.46 g kg−1 body weight of the Swiss mice. The ISA Brown layers of 16 to 18-week-old were immunized intramuscularly with the Vietnamese cobra Naja Naja venom at 0.5 mg kg−1 body weight of the layers. The specific anti-venom antibodies were presented in both serum and egg yolk at 14 days, reached to highest antibody titer at 49 to 56 days and lasted up to 111 days post-immunization. The IgY antibodies purified from the egg yolk revealed potential neutralization and protection of Vero cells and Swiss mice from toxicity of the Vietnamese cobra Naja Naja venom. To the best of our knowledge, this study result is the first cobra snake anti-venom developed in laying hens against the Vietnamese cobra Naja Naja venom. Further study is needed to whether this specific IgY anti-venom antibodies can be used as an antibody therapy for treatment of venomous snake bites in the future.

A Rapid and International Applicable Diagnostic Device for Cobra (Genus Naja) Snakebites.

Cobra snakes (genus Naja) are some of the most dangerous snake species in Asia and Africa, as their bites cause severe life-threatening respiratory failure and local tissue destruction, especially in the case of late diagnosis. The differential diagnosis of snakebite envenomation still mainly relies upon symptomatology, the patient’s description, and the experience of physicians. We have designed a rapid test, immunochromatographic test of cobra (ICT-Cobra), which obtained fair results in improving the diagnosis and treatment of Naja (N.) atra snakebites in Taiwan. In this study, we further investigated the feasibility of applying the kit for the detection of other cobra venoms based on the potential interspecies similarity. We firstly demonstrated the cross-reactivity between eight venoms of medically important cobra species and the rabbit anti-N. atra IgG that was used in ICT-Cobra by Western blotting and sandwich enzyme-linked immunosorbent assay. Then, ICT-Cobra was used to detect various concentrations of the eight venoms to elucidate its performance. Noticeable correlations between the cross-reactivity of venoms from genus Naja snakes and existing geographical characteristics were found. ICT-Cobra could detect venoms from other Asian cobras with variable detection limits comparable to those observed for N. atra, but the kit was less successful in the detection of venom from African cobras. The similar but slightly different venom components and the interaction between venom and rabbit anti-N. atra IgG led to variations in the detection limits. The transcontinental usage of ICT-Cobra might be possible due to the cross-reactivity of antibodies and similarities among the larger-sized proteins. This study showed that the close immunological relationships in the genus Naja could be used to develop a venom detection kit for the diagnosis of cobra envenomation in both Asian and African regions. Additional clinical studies and technical adjustments are still needed to improve the efficacy and broadening the application of ICT-Cobra in the future.

The anti-rabies activity of Caspian cobra venom

Rabies is acute encephalitis that continuously kills thousands of people annually. There is no clinical cure for rabies so far and its prevention is limited to sero-vaccinations based on standard WHO protocols. Certain compounds such as snake venoms contain active biological components with tendency toward acetylcholine receptors and ion channels at the cell surface. These compounds then are able to reduce aggregation of the virus in neuromuscular junction that may lead to inhibit the virus activity. In this study we worked on cytotoxicity and antiviral activity effects of Naja naja oxiana (Iranian Caspian cobra) snake venom components, on Rabies Lyssavirus (Rabies virus; RABV) infected mammalian cells. The concentration of 25 μg/ml F5 fraction separated by FPLC showed minor toxicity on BHK-21 cells by MTT test and high antiviral activity against infected cells by FAT assay. Further studies on F5 fractionation by HPLC showed that the proliferation of infected BHK-21 cells by rabies virus CVS-11 strain was decreased up to 80% by using 20 μg/ml P5 peak, after 48 h. We assume that P5-peptide (MW < 10 kDa) enters the cells through AChR receptors same as rabies virus without competition in binding to the cell receptors and is able to reduce the virus proliferation on post viral infection phase. This is the first report of the presence of an anti-rabies effect of Caspian cobra snake venom component. As per our results the P5 peak is a suitable candidate for further studies as a new agent to reduce CVS-11 rabies virus.

Protein Identification of Venoms of the African Spitting Cobras, Naja mossambica and Naja nigricincta nigricincta

Cobra snakes, including Naja mossambica and Naja nigricincta nigricincta, are one of the major groups of snakes responsible for snakebites in southern Africa, producing significant cytotoxicity and tissue damage. The venom of N. mossambica has been briefly characterised, but that of N. n. nigricincta is not reported. The current study identifies the venom proteins of N. mossambica and N. n. nigricincta. This is achieved using sodium dodecyl sulphate (SDS)-polyacrylamide gel eletrophroresis (PAGE), followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Most of the proteins were less than 17 kDa in both snakes. N. mossambica was found to have 75 proteins in total (from 16 protein families), whereas N.n. nigricincta had 73 (from 16 protein families). Of these identified proteins, 57 were common in both snakes. The proteins identified belonged to various families, including the three-finger toxins (3FTx), Cysteine-rich secretory proteins (CRiSP), Phospholipase A2 (PLA2) and Venom metalloproteinase M12B (SVMP). The current study contributes to the profile knowledge of snake venom compositions, which is of fundamental value in understanding the proteins that play a major role in envenomation.

Public Health Relevance of Sparganosis in Javan Spitting Cobra Snakes (Naja sputatrix): A Neglected Zoonotic Disease In Indonesia

Sparganosis is a zoonotic disease caused by the spargana (larvae) of Spirometra sp. (Diphyllobothriidae).Snakeare particularly important intermediate hosts for the transmission of this parasite in Asia especiallyIndonesia. However, their role for sparganosis in javan spitting cobra (Najasputatrix) is unrecognized. Thisstudy aimsto investigate the infection of cobra snakes with Spirometra tapeworm in Banyuwangi, Indonesiawhere several local sellers have been identified recently sold snakes meat for culinary purposes. A totalof 37 cobra samples were bought from a localseller and euthanized. Then, continued with necropsy andparasitological examination. The result founds 71 plerocercoids within muscular and subcutaneous tissues andthe prevalence were recorded at 56,7%.Our finding is the first identification confirmed record of Spirometratape worm in javan spitting cobra in Indonesia. Since snakes are often a component of mammalian diet,they can be a source of Spirometra tapeworm infection in human and Indonesian wildlife. However, furtherstudies are needed to investigate the prevalence ofinfection in other reptiles and amphibian hosts.

The In Vitro Study of Anti-leishmanial Effect of Naja naja oxiana Snake Venom on Leishmania major.

Although a majority of patients with cutaneous leishmaniasis (CL) are healed with Glucantime chemotherapy, the increased drug resistance rate following its application is a concern. In this study, Naja naja oxiana crude venom of cobra snakes was used for the first time as an assembled combination of bioactive pharmaceutical components on Leishmania major (L. major) standard strain. To evaluate the efficacy of the Naja naja oxiana crude venom of Iranian cobra snakes on Leishmania major standard strain in vitro. Five concentrations (1.25, 2.5, 5, 10 and 20 μg/mL) of venom were added to Leishmania major cultures at 24, 48 and 72 h. The viability of the parasites and venom toxicity were assessed by MTT test. The apoptosis was determined by flow cytometry, while IC50 was determined by counting parasites compared to that of glucantime. Each test was conducted in triplicate. After the exposure of the venom for 72 h, IC50 value was 0.36 μg/mL and 14.12 μg/mL for promastigotes and amastigotes, respectively. MTT valuation clarified 1.01% promastigotes viability. Furthermore, the results indicated that the venom of Naja naja oxiana induced early and late apoptosis in parasites. The venom of Naja naja oxiana revealed remarkable anti-leishmanial effects as a novel anti-parasitic alternative. Thus, the bioactive and effective fractions of this venom may be considered as anti-leishmanial candidates in future studies.

Comparative ameliorative actions of extracted bradykinin potentiating fraction from cobra snake venom and synthetic antioxidants on hepatic tissue of aflatoxicosed rats

ABSTRACT Mycotoxins are secondary metabolites produced by Aspergillus, Penicillium and other genera which contaminate food and exhibit hazardous effects on humans and animals. Aflatoxins (AFs) caused liver necrosis, fibrosis. In the present study, we planned to evaluate the action of bradykinin potentiating factor (BPF) extracted from Egyptian cobra snake venom and synthetic antioxidants; butylated hydroxytoluene (BHT) and oltipraz (OPZ) on the hepatic tissue of aflatoxicosed rats. Aflatoxicosis caused a significant increase of nitric oxide (NO) and lipid peroxidation as malondialdehyde (MDA) associated with a significant decrease in the level of total thiols, glutathione (GSH), and the activities of glutathione peroxidase (GPx) and transferase (GST). In addition to a decrease in the counts of white blood cells (WBCs), lymphocytes (LYM), monocytes (MONO), eosinophils (EOS), red blood cells (RBCs) and an increase in neutrophil counts (NEUT) as well as a significant decrease in the gene expression of hepatic interleukin-1β (Il-1β). The previous changes were confirmed by histopathological alterations. Treatment of aflatoxicosed rats with any of BPF, BHT or OPZ resulted in amelioration of the oxidative stress parameters, blood picture and hepatic IL-1β with improvement in histological features. In conclusion, either BPF, BHT or OPZ can be used for the treatment of aflatoxicosis.