The dose-dependent effect of grayanotoxin on the cardiovascular system

Mad honey (grayanotoxin, GTX) poisoning is caused by a toxin binding to the sodium channels of a cell membrane. This study investigates the dose-dependent effect of GTX on the cardiovascular system. Materials and methods: Twenty-four male Sprague Dawley rats were divided into 4 equal groups. Group 1 was the control group and was administered only saline. GTX-III was administered in doses of 200, 400, and 800 µg/kg for Groups 2, 3, and 4, respectively. After GTX-III injection, blood pressure and heart rate were recorded using an electrophysiological data acquisition system. Results: After 200 µg/kg GTX-III injection, at 31-60 min, the blood pressure decreased significantly from the 84 ± 8 mmHg value of the control group to 53 ± 4 mmHg (P = 0.023). In the group to which 800 µg/kg GTX-III was administered, the blood pressure decreased to 50 ± 7 mmHg and 54 ± 5 mmHg in the postinjection periods of 31-60 and 61-90 min, respectively. These values were significantly different from the 70 ± 6 and 84 ± 8 mmHg values recorded for the control group. The heart rate in the group injected with 400 µg/kg GTX-III decreased significantly 40 min after injection. In the 800 µg/kg GTX-III group, the heart rate decreased significantly 20 min after injection. Conclusion: According to our findings, the bradycardiac and hypotensive picture seen in patients applying to the clinic with mad honey poisoning also emerges clearly in experimental animals at the high dose of 800 µg/kg GTX-III.

The dose-dependent effect of grayanotoxin on the cardiovascular system

Mad honey (grayanotoxin, GTX) poisoning is caused by a toxin binding to the sodium channels of a cell membrane. This study investigates the dose-dependent effect of GTX on the cardiovascular system. Materials and methods: Twenty-four male Sprague Dawley rats were divided into 4 equal groups. Group 1 was the control group and was administered only saline. GTX-III was administered in doses of 200, 400, and 800 µg/kg for Groups 2, 3, and 4, respectively. After GTX-III injection, blood pressure and heart rate were recorded using an electrophysiological data acquisition system. Results: After 200 µg/kg GTX-III injection, at 31-60 min, the blood pressure decreased significantly from the 84 ± 8 mmHg value of the control group to 53 ± 4 mmHg (P = 0.023). In the group to which 800 µg/kg GTX-III was administered, the blood pressure decreased to 50 ± 7 mmHg and 54 ± 5 mmHg in the postinjection periods of 31-60 and 61-90 min, respectively. These values were significantly different from the 70 ± 6 and 84 ± 8 mmHg values recorded for the control group. The heart rate in the group injected with 400 µg/kg GTX-III decreased significantly 40 min after injection. In the 800 µg/kg GTX-III group, the heart rate decreased significantly 20 min after injection. Conclusion: According to our findings, the bradycardiac and hypotensive picture seen in patients applying to the clinic with mad honey poisoning also emerges clearly in experimental animals at the high dose of 800 µg/kg GTX-III.

___

  • Gunduz A, Turedi S, Russell RM, Ayaz FA. Clinical review of grayanotoxin/mad honey poisoning past and present. Clin Toxicol 2008; 46: 437–42.
  • Gunduz A, Bostan H, Turedi S, Nuhoglu I, Patan T. Wild flowers and mad honey. Wilderness Environ Med 2007; 18: 69–
  • Avcı M. Orman gülleri (Rhododendron L.) ve Türkiye’deki doğal yayılışları. İstanbul Üniversitesi Edebiyat Fakültesi Coğrafya Bölümü Coğrafya Dergisi 2004; 12: 13–29 (in Turkish).
  • Kurtoğlu S. Zehirlenmeler, Teşhis ve Tedavi. Kayseri: Erciyes Üniv. Yayınları 1992; 30: 569–70 (in Turkish).
  • Koca I, Koca FA. Poisoning by mad honey: a brief review. Food Chem Toxicol 2007; 45: 1315–8.
  • Eller P, Hochegger K. Honey intoxication and the BezoldJarisch reflex. Int J Cardiol 2010; 8: 144.
  • Seyamal I, Yamaoka K, Yakehiro M, Yoshioka Y, Morihara K. Is the site of action of grayanotoxin in the sodium channel gating of squid axon? Jpn J Physiol 1985; 35: 401–10.
  • Onat F, Yegen BC, Lawrence R, Oktay A, Oktay S. Site of action of grayanotoxins in mad honey in rats. J Appl Toxicol 1991; 3: 199–201.
  • Öztaşan N, Altınkaynak K, Akçay FA, Göçer F, Dane Ş. Effects Of mad honey on blood glucose and lipid levels in rats with streptozocin-induced diabetes. Turk J Vet Anim Sci 2005; 29: 1093–6.
  • Bostan M, Bostan H, Kaya AO, Bilir O, Satiroglu O, Kazdal H et al. Clinical events in mad honey poisoning: a single centre experience. Bull Environ Contam Toxicol 2010; 84: 19–22.
  • Gunduz A, Meric ES, Baydin A, Topbas M, Uzun H, Turedi S et al. Does mad honey poisoning require hospital admission? Am J Emerg Med 2009; 27: 424–7.
  • Demir Akca AS, Kahveci FO. An indispensable toxin known for 2500 years: victims of mad honey. Turk J Med Sci 2012; 42: 1499–504.
  • Gündüz A, Aydın M, Akça M, Türkmen S, Türedi S, Eryiğit U et al. Is grayanotoxin directly responsible for mad honey poisoning-associated seizures. Turk J Med Sci 2012; 42: 1086–
  • Onat FY, Yegen BC, Lawrence R, Oktay A, Oktay S. Mad honey poisoning in man and rat. Rev Environ Health 1991; 9: 3–9.
  • Kim SE, Shin MC, Akaike N, Kim CJ. Presynaptic effects of grayanotoxin III on excitatory and inhibitory nerve terminals in rat ventromedial hypothalamic neurons. Neurotoxicology 2010; 31: 230–8.
  • Terai T, Osakabe K, Katai M, Sakaguchi K, Narama I, Matsuura T et al. Preparation of 9-hydroxy grayanotoxin derivatives and their acute toxicity in mice. Chem Pharm Bull (Tokyo) 2003; 51: 351–3.
  • Maejima H, Kinoshita E, Seyama I. Distinct site regulating grayanotoxin binding and unbinding to D4S6 of Nav1.4 sodium channel as revealed by improved estimation of toxin sensitivity. J Biol Chem 2003; 278: 9464–71.
  • Gunduz A, Durmus I, Turedi S, Nuhoglu I, Ozturk S. Mad honey poisoning-related asystole. Emerg Med J 2007; 24: 592–
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Prevalence of type 1 diabetes mellitus in school children 6 18 years old in Diyarbakır, Southeastern Anatolian Region of Turkey

Hüseyin DEMİRBİLEK, Mehmet Nuri ÖZBEK

Variations of transverse foramens of cervical vertebrae: a 3-dimensional multidetector CT study

Bumin DEĞİRMENCİ, Ömer YILMAZ

Evaluation of early corneal topographic changes in children with Down syndrome

Murat ASLANKURT, Lokman ASLAN, Adnan AKSOY, Muhammed Mustafa KURT, Murat ÖZDEMİR

The effect of chloroquine treatment in malignant astrocytomas on prognosis

Turgay BULUT, Mehmet Ali EKİCİ, Bülent TUCER, Seyit Kaan BAŞARSLAN

One single-tube PCR assay to detect both CD17 (A>T) and IVS-II nt-654 (C>T) homozygous mutations of β-thalassemia

Qi LIU, Jun-Li WANG, Guo-Can YANG, Xue-Jun DONG, Zong-Xin WANG, Guo-Xing GE, Xiao-Feng GU

Protective effect of vardenafil on ischemia reperfusion injury in rat ovary

Mustafa KARA, Hatice BAŞ, Dilek PANDIR, Özlem KARA

Influence of alpha lipoic acid on epithelial apoptosis in experimental periodontitis

Adem KARA, Sümeyra AKMAN, Tevfik DEMİRCİ, Taner ARABACI

Prediction of neurological outcome using bispectral index in patients with severe acute brain injury

Wang XIFENG, Zhang LIANSHUANG, Wu DAWEI

Orthophenylphenol in healthcare environments: a trial related to a new administration method and a review of the literature

Alicem TEKİN, Tuba DAL, Caferi Tayyar SELÇUK, Özcan DEVECİ

The dose-dependent effect of grayanotoxin on the cardiovascular system

Süha TÜRKMEN, Ülkü KARAGÖZ, Abdulkadir GÜNDÜZ, Süleyman TÜREDİ, Metehan AKÇA, Mehmet YILDIRIM