Evaluation of Bee Venom Induced Toxicity: Toxicity and Management

Yıl 2025, Cilt: 10 Sayı: 4, 514 - 520, 31.07.2025

Sıdıka Genç , Kübra Karabulut , Esmanur Niğde , Şevval Büyükgöçmen , Ali Taghizadehghalehjoughi

https://doi.org/10.35229/jaes.1658697

Öz

Inflammation and increased cellular ROS levels caused by bee venom can increase formation of necrotic tissue and allergies. Many methods are used for bee venom induced toxicity. Two agents with therapeutic effects and pharmacological value have been included in these treatment options to decrease induced toxicity. L-tryptophan causes a decrease in the level of inflammation and the amount of ROS. Similarly, Amygdalin, which also targets the mTOR/AKT pathway and reduces inflammation, causes a decrease in FAK, ILK and β-catenin concentrations by inhibiting the expression of β1 and β4 integrins. Application of high doses of bee venom causes sensitization of nociceptors by activating TRPV1 via PLA2 cascade, which contains mellitin. This may result in pain and inflammation. We aimed to examine the toxic effects of bee venom by creating a wound model in the fibroblast cell line. After a linear wound was opened, the cells were exposed to bee venom (25 mg/ml) for 15 minutes. L-tryptophan and Vit B17 doses were applied at the end of 15 minutes. After 24 hours of incubation, wound healing was visualized and cell viability and oxidative damage tests were performed. The results showed that especially BV+ B17 + LT had a 60% effect on viability compared to the bee venom control group, resulting in wound closure. It was also determined that cellular ROS level decreased. All these results show that the combination of L-tryptophan and amygdalin has therapeutic efficacy on difficult-to-heal wounds.

Anahtar Kelimeler

Bee Venom , L-Tryptophan , Toxicity; , B17 , NO

Arı Zehiri Kaynaklı Toksisitenin Değerlendirilmesi: Toksisite ve Yönetim

Öz

Arı zehrinin neden olduğu iltihaplanma ve artan hücresel ROS seviyeleri nekrotik doku oluşumunu ve alerjileri artırabilir. Arı zehri kaynaklı toksisite için birçok tedavi yöntemi kullanılmaktadır. İndüklenen toksisiteyi azaltmak için seçeneklerin terapötik etkileri ve farmakolojik değeri olan iki ajan dahil edilmiştir. L-triptofan iltihaplanma seviyesinde ve ROS miktarında azalmaya neden olur. Benzer şekilde mTOR/AKT yolunu da hedef alan ve iltihaplanmayı azaltan Amigdalin, β1 ve β4 integrinlerinin ekspresyonunu inhibe ederek FAK, ILK ve β-katenin konsantrasyonlarında azalmaya neden olur. Yüksek dozda arı zehri uygulaması, mellitin içeren PLA2 kaskadı aracılığıyla TRPV1'i aktive ederek nosiseptörlerin duyarlılaşmasına neden olur. Bu durum ağrı ve iltihaplanmaya neden olabilir. Fibroblast hücre hattında bir yara modeli oluşturarak arı zehrinin toksik etkilerini incelemeyi amaçladık. Doğrusal bir yara açıldıktan sonra hücreler 15 dakika boyunca arı zehrine (25 mg/ml) maruz bırakıldı. 15 dakikanın sonunda L-triptofan ve Vit B17 dozları uygulandı. 24 saatlik inkübasyondan sonra yara iyileşmesi görüntülendi ve hücre canlılığı ve oksidatif hasar testleri yapıldı. Sonuçlar özellikle BV+ B17 + LT dozunun arı zehri kontrol grubuna göre canlılık üzerinde %60 etkiye sahip olduğunu ve yaranın kapandığını gösterdi. Ayrıca hücresel ROS düzeyinin azaldığı belirlendi. Tüm bu sonuçlar L-triptofan ve amigdalin kombinasyonunun iyileşmesi zor yaralarda terapötik etkinliğe sahip olduğunu göstermektedir.

Anahtar Kelimeler

Arı Zehiri , Toksisite , L-Triptofan , B17 , NO

Kaynakça

• Addis, R., Cruciani, S., Santaniello, S., Bellu, E., Sarais, G., Ventura, C., ..., & Pintore, G. (2020). Fibroblast proliferation and migration in wound healing by phytochemicals: evidence for a novel synergic outcome. International Journal of Medical Sciences, 17(8), 1030.
• Agarwal, P., Singh, D., Raisuddin, S., & Kumar, R. (2020). Amelioration of ochratoxin-A induced cytotoxicity by prophylactic treatment of N- Acetyl-L-Tryptophan in human embryonic kidney cells. Toxicology, 429, 152324. DOI: 10.1016/j.tox.2019.152324
• Al-Khafaji, K., & Tok, T.T. (2020). Molecular dynamics simulation, free energy landscape and binding free energy computations in exploration the anti- invasive activity of amygdalin against metastasis. Computer Methods and Programs in Biomedicine, 195, 105660.
• Al-Otaibi, A.M. (2024). Therapeutic effects of vitamin B17 against anabolic steroid Trenorol induced testicular toxicity, injury, DNA damage and apoptosis in male rats. Toxicol Res (Camb), 13(2), tfae084. DOI: 10.1093/toxres/tfae084
• Avci, S., Gunaydin, S., Ari, N. S., Karaca Sulukoglu, E., Polat, O.E., Gecili, I., ..., & Hacimuftuoglu, A. (2022). Cerebrolysin alleviating effect on glutamate-mediated neuroinflammation via glutamate transporters and oxidative stress. Journal of Molecular Neuroscience, 72(11), 2292-2302.
• Bomalaski, J.S., Neilson, E., & Jimenez, S.A. (1986). Regulation of fibroblast proliferation and collagen synthesis by cytokines. Immunology Today, 7(10), 303-307.
• Celebi, D., Celebi, O., Baser, S., & Taghizadehghalehjoughi, A. (2023). Evaluation of antimicrobial and antibiofilm efficacy of bee venom and exosome against Escherichia coli K99 strain. Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 29(3).
• Comakli, S., Sevim, C., Kontadakis, G., Dogan, E., Taghizadehghalehjoughi, A., Ozkaraca, M., ..., & Tsatsakis, A. (2019). Acute glufosinate-based herbicide treatment in rats leads to increased ocular interleukin-1beta and c-Fos protein levels, as well as intraocular pressure. Toxicol. Rep., 6, 155-160. DOI: 10.1016/j.toxrep.2019.01.004
• Dasari, P.K., Raja, J.K., Kumar, P.P., Durga, G., Shiva, Y., & Bhavani, D. (2024). A Review on Vitamin B 17 (Amygdalin). Int. J. Sci. R. Tech., 1(3).
• Eron, L.J. (1999). Targeting lurking pathogens in acute traumatic and chronic wounds. The Journal of emergency medicine, 17(1), 189-195.
• Felemban, S.G., Aldubayan, M.A., Alhowail, A.H., & Almami, I.S. (2020). Vitamin B17 Ameliorates Methotrexate-Induced Reproductive Toxicity, Oxidative Stress, and Testicular Injury in Male Rats. Oxid Med Cell Longev, 2020, 4372719. DOI: 10.1155/2020/4372719
• Florido, J., Rodriguez-Santana, C., Martinez-Ruiz, L., López-Rodríguez, A., Acuña-Castroviejo, D., Rusanova, I., & Escames, G. (2022). Understanding the mechanism of action of melatonin, which induces ROS production in cancer cells. Antioxidants, 11(8), 1621.
• Genç, S., Karabulut, K., Niğde, E., Aydin, Y.E., Aydın, B., Aydın, A.E., & Taghizadehghalehjoughi, A. (2024). Amygdalin (Vitamin B17) Effect on Glioblastoma: Focus on Oxidant Capacity and Antioxidant Status. Recent Trends in Pharmacology, 2(2), 75-78.
• Khalil, A., Elesawy, B.H., Ali, T.M., & Ahmed, O.M. (2021). Bee venom: From venom to drug. Molecules, 26(16), 4941.
• Lee, G., & Bae, H. (2016). Anti-inflammatory applications of melittin, a major component of bee venom: Detailed mechanism of action and adverse effects. Molecules, 21(5), 616.
• Lee, H.-S., Kim, Y.S., Lee, K.S., Seo, H.S., Lee, C.Y., & Kim, K.K. (2021). Detoxification of bee venom increases its anti-inflammatory activity and decreases its cytotoxicity and allergenic activity. Applied Biochemistry and Biotechnology, 193, 4068-4082.
• Liczbiński, P., & Bukowska, B. (2018). Molecular mechanism of amygdalin action in vitro: review of the latest research. Immunopharmacology and Immunotoxicology, 40(3), 212-218.
• Maes, M., Meltzer, H.Y., Scharpè, S., Bosmans, E., Suy, E., De Meester, I., ..., & Cosyns, P. (1993). Relationships between lower plasma L- tryptophan levels and immune-inflammatory variables in depression. Psychiatry Research, 49(2), 151-165.
• Mannino, G., Caradonna, F., Cruciata, I., Lauria, A., Perrone, A., & Gentile, C. (2019). Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleuki n‐1β. Journal of Pineal Research, 67(3), e12598.
• Nalci, O.B., Nadaroglu, H., Genc, S., Hacimuftuoglu, A., & Alayli, A. (2020). The effects of MgS nanoparticles-Cisplatin-bio-conjugate on SH- SY5Y neuroblastoma cell line. Molecular Biology Reports, 47, 9715-9723.
• Oršolić, N. (2012). Bee venom in cancer therapy. Cancer and Metastasis Reviews, 31, 173-194.
• Özkorkmaz, E.G., & Özay, Y. (2009). Yara iyileşmesi ve yara iyileşmesinde kullanılan bazı bitkiler. Türk Bilimsel Derlemeler Dergisi, 2, 63-67.
• Quy Huong, D., Dinh Tu Tai, P., Quang Trung, N., Thong, N.M., Tam, N.M., Hai Phong, N., & Nam, P.C. (2024). Investigation of the free radical scavenging ability of l-tryptophan and its derivatives using experimental methods and quantum chemical calculations. RSC Adv, 14(51), 38059-38069. DOI: 10.1039/d4ra06729k
• Sevim, Ç., Taghizadehghalehjoughi, A., & Mehtap, K. (2020). In vitro investigation of the effects of imidacloprid on AChE, LDH, and GSH levels in the L-929 fibroblast cell line. Turkish Journal of Pharmaceutical Sciences, 17(5), 506.
• Shizuma, T., Mori, H., & Fukuyama, N. (2013). Protective effect of tryptophan against dextran sulfate sodium- induced experimental colitis. Turk J. Gastroenterol., 24(1), 30-35. DOI: 10.4318/tjg.2013.0558
• Tepebaşı, M.Y., & Calapoğlu, N.Ş. (2016). Yara iyileşmesinin hücresel ve moleküler mekanizması. Medical Journal of Suleyman Demirel University, 23(4).
• Wei, X., Li, D., Feng, C., Mao, H., Zhu, J., Cui, Y., ..., & Wang, C. (2022). Effects of hydrogen peroxide and l-tryptophan on antioxidative potential, apoptosis, and mammalian target of rapamycin signaling in bovine intestinal epithelial cells. J Dairy Sci, 105(12), 10007-10019. DOI: 10.3168/jds.2022-21869.