BACKGROUND: Bee venom (BV) has been widely investigated for potential medical uses. Recent inadvertent uses of BV based products have shown to mitigate signs of fungal infections. However, the component mediating the antifungal effect has not been identified. OBJECTIVE: This investigation compares bee venom in its whole and partial forms to evaluate the possible component responsible for the antifungal effect. METHODS: Forty-eight plates inoculated with Trichophyton rubrum were allocated into four groups. The groups were treated with raw BV (RBV), melittin, apamin and BV based mist (BBM) respectively and each group was further allocated accordingly to three different concentrations. The areas were measured every other day for 14 days to evaluate the kinetic changes of the colonies. RESULTS: The interactions of ratio differences over interval were confirmed in groups treated with RBV and BBM. In RBV, the level of differences were achieved in groups treated with 10 mg/100 µl (p=0.026) and 40 mg/100 µl (p=0.000). The mean difference of ratio in groups treated with RBV was evident in day 3 and day 5. The groups that were treated with melittin or apamin did not show any significant interaction. In BBM groups, the significant levels of ratio differences over time intervals were achieved in groups treated with 200 µl/100 µl (p=0.000) and 300 µl/100 µl (p=0.030). CONCLUSION: The the bee venom in its whole form delivered a significant level of inhibition and we concluded that the venom in separated forms are not effective. Moreover, BV based products may exert as potential antifungal therapeutics.
Antifungal Agents ; Apamin ; Bee Venoms* ; Bees* ; Melitten ; Negotiating ; Trichophyton* ; Venoms

Honeybee venom consists of melittin, apamin, phospholipase A2, hyaluronidase and other biologically active substances. It can cause potentially lethal reaction after mass envenomation. But, acute renal failure following multiple bee stings is rare and its pathogenesis is not well known. The possible causes of acute renal failure due to multiple bee stings are rhabdomyolysis, hemolysis and direct nephrotoxicity of bee venom. A 60-year-old man was the victim of a bee(Apis mellifera) attack. More than 780 bee stings were found over his face, neck and upper extremities. Gross hematuria, oliguria and generalized edema was developed within a few hours. He has fully recovered after general supportive care including hemodialysis. This case demonstrates that multiple bee stings may cause rhabdomyolysis with consequent acute renal failure.
Acute Kidney Injury* ; Apamin ; Bee Venoms ; Bees ; Bites and Stings* ; Edema ; Hematuria ; Hemolysis ; Humans ; Hyaluronoglucosaminidase ; Melitten ; Middle Aged ; Neck ; Oliguria ; Phospholipases A2 ; Renal Dialysis ; Rhabdomyolysis* ; Upper Extremity ; Venoms

The present study was undertaken to confirm whether melittin, a major constituent of whole bee venom (WBV), had the ability to produce the same nociceptive responses as those induced by WBV. In the behavioral experiment, changes in mechanical threshold, flinching behaviors and paw thickness (edema) were measured after intraplantar (i.pl.) injection of WBV (0.1 mg & 0.3 mg/paw) and melittin (0.05 mg & 0.15 mg/paw), and intrathecal (i.t.) injection of melittin (6microgram). Also studied were the effects of i.p. (2 mg & 4 mg/kg), i.t. (0.2microgram & 0.4microgram) or i.pl. (0.3 mg) administration of morphine on melittin- induced pain responses. I.pl. injection of melittin at half the dosage of WBV strongly reduced mechanical threshold, and increased flinchings and paw thickness to a similar extent as those induced by WBV. Melittin- and WBV-induced flinchings and changes in mechanical threshold were dose- dependent and had a rapid onset. Paw thickness increased maximally about 1 hr after melittin and WBV treatment. Time-courses of nociceptive responses induced by melittin and WBV were very similar. Melittin-induced decreases in mechanical threshold and flinchings were suppressed by i.p., i.t. or i.pl. injection of morphine. I.t. administration of melittin (6microgram) reduced mechanical threshold of peripheral receptive field and induced flinching behaviors, but did not cause any increase in paw thickness. In the electrophysiological study, i.pl. injection of melittin increased discharge rates of dorsal horn neurons only with C fiber inputs from the peripheral receptive field, which were almost completely blocked by topical application of lidocaine to the sciatic nerve. These findings suggest that pain behaviors induced by WBV are mediated by melittin-induced activation of C afferent fiber, that the melittin- induced pain model is a very useful model for the study of pain, and that melittin-induced nociceptive responses are sensitive to the widely used analgesics, morphine.
Analgesics ; Bee Venoms* ; Bees* ; Lidocaine ; Melitten* ; Morphine ; Nerve Fibers, Unmyelinated ; Nociception ; Posterior Horn Cells ; Sciatic Nerve

Whole bee venom (WBV) and its major component, melittin, have been reported to induce long-lasting spontaneous flinchings and hyperalgesia. The current study was designed to elucidate the peripheral and spinal mechanisms of N-methyl-D-aspartate (NMDA) and non-NMDA receptors by which intraplantar (i.pl.) injection of WBV and melittin induced nociceptive responses. Changes in mechanical threshold and flinching behaviors were measured after the injection of WBV (0.04 mg or 0.1 mg/paw) and melittin (0.02 mg or 0.05 mg/paw) into the mid-plantar area of a rat hindpaw. MK-801 and CNQX (6-cyano-7-nitroquinoxaline-2, 3-dione disodium) were administered intrathecally (i.t. 10microgram) or i.pl. (15microgram) 15 min before or i.t. 60 min after i.pl. WBV and melittin injection. Intrathecal pre- and post- administration of MK-801 and CNQX significantly attenuated the ability of high dose WBV and melittin to reduce paw withdrawal threshold (PWT). In the rat injected with low dose, but not high dose, of WBV and melittin, i.pl. injection of MK-801 effectively suppressed the decrease of PWTs only at the later time-points, but the inhibitory effect of CNQX (i.pl.) was significant at all time-point after the injection of low dose melittin. High dose WBV- and melittin-induced spontaneous flinchings were significantly suppressed by i.t. administration of MK-801 and CNQX, and low dose WBV- and melittin-induced flinchings were significantly reduced only by intraplantarly administered CNQX, but not by MK-801. These experimental flinchings suggest that spinal, and partial peripheral mechanisms of NMDA and non-NMDA receptors are involved in the development and maintenance of WBV- and melittin-induced nociceptive responses.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Animals ; Bee Venoms* ; Bees* ; Dizocilpine Maleate ; Hyperalgesia ; Melitten* ; N-Methylaspartate* ; Rats*

OBJECTIVES: Bee venom contains a potent antiinflammatory peptide 401 as well as mellitin. The purpose of this study was to see the efficacy and safety of purified bee venom injection therapy for knee or spinal osteoarthritis patients. METHODS: One hundred and one osteoarthritis patients were randomly assigned to bee venom injection therapy or oral nabumetone medication group. Bee venom injection group was subdivided into 3 groups according to different dosing schedule(group A: gradual increase up to 0.7mg, group B: up to 1.5mg and group C: up to 2.0mg). Control group patients(group D) were given 1000mg nabumetone daily for 6 weeks. There were 25, 26, 25, and 26 patients assigned to A, B, C, or D group. The efficacy of treatment was evaluated by measuring instruments developed by authors, and the safety of bee venom injection was evaluated by hematology and chemistry laboratory examination. RESULTS: Among 101 patients, eighty-one patients completed the study, but twenty patients were dropped out and two of these patients were dropped out due to adverse drug reaction. The efficacy in bee venom group showed better improvement than nabumetone group(p<0.01). Within bee venom group, group B and C showed better improvement than group A(p<0.01). Itching around injection site occurred in most patients, and bodyache occurred in 49 patients (81.7%). Hemoglobin was decreased(0.3g/dl) in group C, but no significant changes were observed in other laboratory values. CONCLUSION: The efficacy of bee venom injection in the control of knee or back pain in osteoarthritis patients was better than nabumetone medication. No severe allergic or adverse reaction was observed in bee venom treatment patients, but problems related with bee venom injection, such as pruritis, bodyache, and the possibility of anaphylaxis, should be considered for the use of bee venom injection.
Anaphylaxis ; Back Pain ; Bee Venoms* ; Bees* ; Chemistry ; Drug-Related Side Effects and Adverse Reactions ; Hematology ; Humans ; Knee ; Melitten ; Osteoarthritis* ; Osteoarthritis, Spine ; Pruritus

Melittin, a major component of bee venom, produces a sustained decrease in mechanical threshold, and an increase in spontaneous flinchings and paw thickness, which are characteristics similar to those induced by whole bee venom. Melittin-induced nociception has been known to be modulated by the changes in the activity of excitatory amino acid receptors, voltage-dependent calcium channels, cyclooxygenase and serotonin receptors. The present study was undertaken to investigate the role of calcium chelators (TMB-8 & Quin 2) in melittin-induced nociceptive responses. Changes of mechanical threshold and spontaneous flinching behaviors were measured at a given time point following intraplantar injection of melittin (30microgram/paw). Intrathecal or intraplantar pre-administration and intrathecal post-treatment of TMB-8 and Quin 2 significantly prevented the melittin-induced reduction of mechanical threshold, and intraplantar or intrathecal pre-treatment of TMB-8 and Quin 2 suppressed melittin-induced flinching behaviors. These results indicate that calcium ion in the spinal dorsal horn neurons and peripheral nerves plays an important role in the production and maintenance of mechanical allodynia and spontaneous pain by melittin.
Animals ; Bee Venoms ; Calcium Channels ; Calcium* ; Chelating Agents ; Hyperalgesia ; Ions* ; Melitten ; Nociception* ; Peripheral Nerves ; Posterior Horn Cells ; Prostaglandin-Endoperoxide Synthases ; Rats* ; Receptors, Glutamate ; Receptors, Serotonin

Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disorder characterized by a selective loss of motor neurons in the spinal cord, brainstem, and motor cortex, leading to weakness of the limb and bulbar muscles. Although the immediate cause of death in ALS is the destruction of motor neurons, ALS is a multi-organ disease that also affects the lungs, spleen, and liver. Melittin is one of components of bee venom and has anti-neuroinflammatory effects in the spinal cord, as shown in an ALS animal model. To investigate the effects of melittin on inflammation in the lungs and spleen, we used hSOD1(G93A) transgenic mice that are mimic for ALS. Melittin treatment reduced the expression of inflammatory proteins, including Iba-1 and CD14 by 1.9- and 1.3-fold (p<0.05), respectively, in the lungs of symptomatic hSOD1(G93A) transgenic mice. In the spleen, the expression of CD14 and COX2 that are related to inflammation were decreased by 1.4 fold (p<0.05) and cell survival proteins such as pERK and Bcl2 were increased by 1.3- and 1.5-fold (p<0.05) in the melittin-treated hSOD1G93A transgenic mice. These findings suggest that melittin could be a candidate to regulate the immune system in organs affected by ALS.
Amyotrophic Lateral Sclerosis* ; Animals* ; Bee Venoms ; Brain Stem ; Cause of Death ; Cell Survival ; Extremities ; Immune System ; Inflammation* ; Liver ; Lung ; Melitten* ; Mice ; Mice, Transgenic ; Models, Animal* ; Motor Cortex ; Motor Neurons ; Muscles ; Neurodegenerative Diseases ; Spinal Cord ; Spleen

Bee venom injection therapy is an alternative treatment sometimes used for chronic inflammatory diseases, including rheumatoid arthritis and multiple sclerosis, to reduce pain. Several chemical components of bee venom have anti-inflammatory effects, and apitoxin, one of the mixed components, has been used for pain prevention therapy. However, there have been no large-scale investigations regarding the efficacy or side effects or apitoxin. In this study, a case of serum sickness reaction that developed after receiving bee venom injection therapy is reported.
Arthritis, Rheumatoid ; Bee Venoms ; Bees ; Multiple Sclerosis ; Serum Sickness ; Skin

Bee venom immunotherapy (b-VIT) can be combined with omalizumab therapy in order to suppress systemic reactions developing due to b-VIT itself. Omalizumab acts as a premedication and gains time for the immunotherapy to develop its immunomodulatory effects. However, the combination of omalizumab and b-VIT is not always effective enough. Herein we present a patient in whom successful immunotherapy cannot be achieved with combination of omalizumab to b-VIT.
Anaphylaxis ; Bee Venoms ; Bees ; Humans ; Immunotherapy ; Omalizumab ; Premedication

Acupuncture ; Acupuncture Therapy/adverse effects* ; Bee Venoms/adverse effects* ; Humans