İvermektin, organik fosforlu insektisitler ve piretroid insektisitlerin toksikolojik etkileşim özellikleri üzerinde deneysel araştırmalar
Loading...
Files
Date
1991
Authors
Sağmanlıgil, Hülya
Journal Title
Journal ISSN
Volume Title
Publisher
Uludağ Üniversitesi
Abstract
Bu araştırmada, ivermektin, organik fosforlu insektisitler (diazinon, fenitrotion) ve piretroid insektisitler (permetrin, fenvalerat) arasında oluşabilecek etkileşimleri ve çeşitli: enzimler, glikoz seviyesi ve kan parametreleri üzerindeki etkilerini belirlemek amacıyla deneysel çalışmalar yapıldı. Çalışmalar 65Q fare ve 40 köpek üzerinde yapıldı. Fareler her birinde on fare bulunan gruplara ayrıldı. Her ilaç için on fare kontrol grubu olarak bırakıldı. İlaçlar, farelere ağız yolu, deri altı ve periton içi yolla uygulanarak 24 saat içindeki ölüm oranları saptandı. LD,_ " dozları, Behrens-Harber yöntemine göre hesaplandı. Belirlenen LD5" dozları sırasıyla; ivermektin için deri altı 0.2925 mg/kg, diazinon için periton içi 165 mg/kg, fenitrotion için oral 1Q30 mg/kg, permetrin için oral 2B75 mg/kg ve fenvalerat için oral 414 mg/kg'dır. LDp.,-, dozlarında meydana gelebilecek değişimleri belirlemek için birinci ilacın verilme yoluna göre emilme süre si kadar beklenildikten sonra ikinci ilaç uygulandı. İvermektinin sağıtım dozunda (D. 2 mg/kg) deri altı yolla verilmesin den sonra, organik fosforlu ve piretroid insektisitler oral ve periton içi yolla uygulanarak LD^dozları yeniden hesaplandı. LD5n dozları; diazinon için periton içi 162.5 mg/kg, fenitro tion için oral 692.5 mg/kg, permetrin için oral 2825 mg/kg, fenvalerat için oral 347.5 mg/kg olarak saptandı. Piretroid insektisitlerin (permetrin, fenvalerat) verilmesinden sonra organik fosforlu insektisitlerin LD5Q dozu yeniden saptandı. -1-Permetrinin subletal dozda (1DDD mg/kg) ağız yoluyla verilme sinden sonra diazinonun LD- dozu 52.5 mg/kg ve fenvaleratın subletal dozda (10G mg/kg) ağız yoluyla verilmesinden sonra fenitfotlonun LD,-n dozu"-S57.5 mğ/kg.olarak belirlendi. Diazinon ve permetrinin ivermektinden sonra verilmesiyle LD(-n dozlarında önemli bir değişim olmamasına karşın, ivermektinden sonra fenitrotion ve fenvaleratın uygulanmasıyla LD,-n dozlarında düşme meydana gelmiş, yani toksisitelerinde artma olmuştur. Piretroid insektisitlerin verilmesinden sonra organik fosforlu insektisitlerin LD dozundaki azalma bu iki insektisit arasında toksisiteyi artırıcı yönde bir etkileşim olduğuna işaret etmektedir. İvermektin, organik fosforlu ve piretroid insektisitlerin çeşitli enzim düzeyleri (ChE, SEDT, SBPT, LDH, GGT) glikoz düzeyi ve kan parametreleri (sedimentasyon, hemoglobin, hematokrit, total lökosit ve total eritrosit) üzerindeki etkilerini belirlemek amacıyla ilaçlar, köpeklere yalnız başına ve birbiri! ardı sıra, deri altı ve periton içi yolla uygulandı. İvermektinin enzim düzeyleri, kan parametreleri ve glikoz düzeyi üzerinde kontrole göre önemli bir değişiklik yapmadığı belirlendi. Drganik fosforlu insektisitlerin (diazinon ve fenitrotion) kûlinesteraz enzim düzeyi üzerinde yaklaşık % 84 ' e varan oranlarda bir inhibisyon yapmasına karşın, piretroid insektisitlerin (permetrin ve fenvalerat) kolinesteraz düzeyi üzerinde etkili olmadığı gözlemlendi. -2-Organik fosforlu ve piretxoiti insektisitlerin karaciğer enzim düzeylerinde (SGDT, SGPT,I_DH) önemli bir artışa ne den olurken EGT aktivitesi üzerinde belirgin bir değişiklik yapmadığı saptandı. Karaciğer enzimlerinde 4. ve 24. saatlerde belirlenen yüksek oranlı artışlar akut bir karaciğer harabiyetinin meydana geldiğine işaret etmektedir. Fenitrotion, permetrin ve fenvaleratın glikoz düzeyinde yaklaşık %10- 33 oranında bir artışa neden olması, hiperglisemiye işaret etmektedir. Organik fosforlu ve piretroid insektisitlerin sedimentasyon değerini değiştirmediği saptandı. Total eritrosit sayısının normale yakın olmasına karşın hemoglobin değerlerinde görülen azalma ile hipokrom bir aneminin meydana geldiği anlaşılmaktadır. Organik fosforlu ve piretroid insektisitlerin 4. ve 24. saatlerde hematokrit ve total lökosit değerlerinde önemli bir artışa neden olduğu belirlendi. Hematokrit değerlerinin kontrole oranla % 5-10 oranındaki artışı ile kanın koyulaştığı söylenebilir. Total lökosit sayısında % 50 oranındaki artış akut zehirlenme sonucunda lökositozisin geliştiğine işaret etmektedir. Organik fosforlu ve piretroid insektisitlerin kendi aralarında ve ivermektinle birlikte uygulanmaları sonucunda enzim ve kan parametrelerinde anlamlı bir değişiklik bulunmadı. Sonuç olarak, antiparaziter ilaçların bir arada kullanılmasıyla toksisiteyi artırıcı yönde bir etkileşimin ortaya çıkabileceği ve bu etkileşimlerin ilaçların bireysel özelliklerine ve hayvan türlerine bağlı olarak değişebileceği daima dikkate alınmalıdır.
In this research some experimental studies were carried Dut to find- probable interactions to be occurred among ivermectin organophosphorous insecticides (diazinon, fenitrothion) and pyrethroid insecticides (permethrin, fenvalerate) and resulted effects on various enzymes, glucose and blood parameters. The experiments were performed on 65D mice and 4Q dogs. All mice were separated into the groups of ten mice. For each drug, ten mice were chosen as control group. The drugs were ad ministered to the mice oral, subcutaneous and intraperitoneal routes and then death rates were determined in 2k hours.LDr"dosEs were calculated according to the Behrens-Karber ' s Method. Findings for LDcn doses are as follows: ivermectin : 0.2925 mg/kg. s.c. Diazinon : 165 mg/kg. i.p. Fenitrothion : 1G3D mg/kg. oral Permethrin : 2875 mg/kg. oral Fenvalerate : 414 mg/kg. oral With respect to the administration route of first drug, the second one was applied after the absorption of first drug to find the changes which might occur at LD doses. Following the subcutaneous administration of ivermectin at the therapeutic dose (D.2 mg/kg), the oral and intraperitoneal.. LD^p doses of -4-organophosphorous and pyrethroid insectiEides were recalculated. In that time, LDcn doses were determined as follows: 162.5 mg/kg. i.p. 692.5 mg/kg. oral 2B25 mg/kg. oral 347.5 mg/kg. oral Diazinon Fenitrothion Permethrin Fenvalerate LD,-n doses of organphosphorous iBsecticides, mere cedeter- mined after pyrethroid insecticides (permethrin, fenvalerate) were given. Following the administration of permethrin at sub lethal dosedOOO mg/kg) by mouth, LD" dose of diazinon was found as 52.5 mg/kg and after fenvalerate at sublethal dose (10D mg/kg) by mouth, LD^-dose of fenitrothion as 657.5 mg/kg. Diazinon and permethrin were administered after iver mectin and there were not any important changes at LD,-n doses, but because of being given of fenitrothion and fenvalerate after ivermectin there were some decreases at LD,-n doses, that's, increase in toxicity were observed. After administering pyrethroid insecticides, the decrease at LD-,, doses of oganophosphorous insecticides indicates an interaction causing to increase the toxicity between these two insecticides. For determining the effects of ivermectin, organophos phorous and pyrethroid insecticides on various: enzyme levels (ChE,SE0T, SEPT, LDH, GET) glucose level and the blood parameters (sedimentation, hematocrit, hemoglobin, total leucocyte and erytrocyte), the drugs were applied to the dogs by subcutaneous or intraperitoneal route in single and one after the other. It was found that ivermectin did not cause any significant change on enzyme levels, blood parameters and glucose level. Although -5-organophosphorous insecticides (diazinon and f enitrothion) inhibited the cholinesterase enzyme approximately at the rate of 84 per cent, it was observed that the pyrethroid insecticides (permethrin and f envalerate) do not effect cholinesterase enzyme. As organophosphorous and. pyrethroid insecticides made important increases at the liver enzyme levels (SEDT, SGPT, LDH) but they did not cause any significant change on EGT activity. High increases found on the fourth and twenty-fourth hour in liver enzymes indicate the presence of an acute liver damage. Fenitrothion jpermethrin and fenvalerate caused the increase of blood glucose approximately at the rate of 10-33 per cent indicating the hyperglycemia. It was observed that the organophosphorous and pyrethroid insecticides do not change the sedimentation value. Although the total erytrocyte level was normal, the decrease of hemoglobin value indicates the occurrence of a hypochromic anemia. It urns marked that organophosphorous and pyrethroid insecticides caused an important increase at the hematocrit and total leucocyte value on the fourth and twenty-f ourth hour. Since hematocrit value increased approximately at the rate of 5-10 per cent when compared with control, it can be said that blood became dense. A 50 per cent elevation at total leucocyte level was found indicating that the leucocytosis = developed due to an acute poisoning. After the application of organophosphorous and pyrethroid insecticides in single or combined and with ivermectin it can not be found significant changes in relation to the enzymes and blood parameters., - b -In conclusion, when antiparasitic drugs were applied simultaneously, it should be taken into consideration that there might be interactions increasing toxicity and these interactions can be changed depending on individual characteristics of drug and animal species. Key words: ivermectin, organophosphorous insecticides (diazinon, f enitrothicn), pyrethrcid insecticides (permethrin, f envalerate), toxicological interactions.
In this research some experimental studies were carried Dut to find- probable interactions to be occurred among ivermectin organophosphorous insecticides (diazinon, fenitrothion) and pyrethroid insecticides (permethrin, fenvalerate) and resulted effects on various enzymes, glucose and blood parameters. The experiments were performed on 65D mice and 4Q dogs. All mice were separated into the groups of ten mice. For each drug, ten mice were chosen as control group. The drugs were ad ministered to the mice oral, subcutaneous and intraperitoneal routes and then death rates were determined in 2k hours.LDr"dosEs were calculated according to the Behrens-Karber ' s Method. Findings for LDcn doses are as follows: ivermectin : 0.2925 mg/kg. s.c. Diazinon : 165 mg/kg. i.p. Fenitrothion : 1G3D mg/kg. oral Permethrin : 2875 mg/kg. oral Fenvalerate : 414 mg/kg. oral With respect to the administration route of first drug, the second one was applied after the absorption of first drug to find the changes which might occur at LD doses. Following the subcutaneous administration of ivermectin at the therapeutic dose (D.2 mg/kg), the oral and intraperitoneal.. LD^p doses of -4-organophosphorous and pyrethroid insectiEides were recalculated. In that time, LDcn doses were determined as follows: 162.5 mg/kg. i.p. 692.5 mg/kg. oral 2B25 mg/kg. oral 347.5 mg/kg. oral Diazinon Fenitrothion Permethrin Fenvalerate LD,-n doses of organphosphorous iBsecticides, mere cedeter- mined after pyrethroid insecticides (permethrin, fenvalerate) were given. Following the administration of permethrin at sub lethal dosedOOO mg/kg) by mouth, LD" dose of diazinon was found as 52.5 mg/kg and after fenvalerate at sublethal dose (10D mg/kg) by mouth, LD^-dose of fenitrothion as 657.5 mg/kg. Diazinon and permethrin were administered after iver mectin and there were not any important changes at LD,-n doses, but because of being given of fenitrothion and fenvalerate after ivermectin there were some decreases at LD,-n doses, that's, increase in toxicity were observed. After administering pyrethroid insecticides, the decrease at LD-,, doses of oganophosphorous insecticides indicates an interaction causing to increase the toxicity between these two insecticides. For determining the effects of ivermectin, organophos phorous and pyrethroid insecticides on various: enzyme levels (ChE,SE0T, SEPT, LDH, GET) glucose level and the blood parameters (sedimentation, hematocrit, hemoglobin, total leucocyte and erytrocyte), the drugs were applied to the dogs by subcutaneous or intraperitoneal route in single and one after the other. It was found that ivermectin did not cause any significant change on enzyme levels, blood parameters and glucose level. Although -5-organophosphorous insecticides (diazinon and f enitrothion) inhibited the cholinesterase enzyme approximately at the rate of 84 per cent, it was observed that the pyrethroid insecticides (permethrin and f envalerate) do not effect cholinesterase enzyme. As organophosphorous and. pyrethroid insecticides made important increases at the liver enzyme levels (SEDT, SGPT, LDH) but they did not cause any significant change on EGT activity. High increases found on the fourth and twenty-fourth hour in liver enzymes indicate the presence of an acute liver damage. Fenitrothion jpermethrin and fenvalerate caused the increase of blood glucose approximately at the rate of 10-33 per cent indicating the hyperglycemia. It was observed that the organophosphorous and pyrethroid insecticides do not change the sedimentation value. Although the total erytrocyte level was normal, the decrease of hemoglobin value indicates the occurrence of a hypochromic anemia. It urns marked that organophosphorous and pyrethroid insecticides caused an important increase at the hematocrit and total leucocyte value on the fourth and twenty-f ourth hour. Since hematocrit value increased approximately at the rate of 5-10 per cent when compared with control, it can be said that blood became dense. A 50 per cent elevation at total leucocyte level was found indicating that the leucocytosis = developed due to an acute poisoning. After the application of organophosphorous and pyrethroid insecticides in single or combined and with ivermectin it can not be found significant changes in relation to the enzymes and blood parameters., - b -In conclusion, when antiparasitic drugs were applied simultaneously, it should be taken into consideration that there might be interactions increasing toxicity and these interactions can be changed depending on individual characteristics of drug and animal species. Key words: ivermectin, organophosphorous insecticides (diazinon, f enitrothicn), pyrethrcid insecticides (permethrin, f envalerate), toxicological interactions.
Description
Keywords
İnsektisidler, Insecticides, İvermectin, Ivermectin
Citation
Sağmanlıgil, H. (1991). İvermektin, organik fosforlu insektisitler ve piretroid insektisitlerin toksikolojik etkileşim özellikleri üzerinde deneysel araştırmalar. Yayınlanmamış doktora tezi. Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.