Downregulation of nicotinic and muscarinic receptor function in rats after subchronic exposure to diazinon
2016
Authors
Ivanović, SašaDimitrijević, Blagoje
Ćupić, Vitomir
Jezdimirović, Milanka
Borozan, Sunčica
Savić, Mila
Savić, Đorđe
Article (Published version)
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Diazinon (DZN) is an organophosphate insecticide which exerts its effect through the inhibition of acetyl cholinesterase enzyme (AChE). In this work, we studied the development of tolerance to subchronic p.o. administration of DZN in rats, under both in vivo and in vitro conditions. A group of 20 rats (2 groups, n = 10) was administered p.o. the 1/10 of established LD50 DZN (namely 55.87 mg/kg bw) for 28 days. On the 14th and 28th day of study with isolated diaphragm and ileum, we examined the downregulation of nicotinic and muscarinic receptor function through Electrical Field Stimulation (EFS). Maximum contractility of the diaphragm was recorded on the 14th day of the study (25% higher compared to the non-treated rats), while on the 28th day the contractions almost did not differ from the values found in non-treated rats. EFS of isolated ileum on the 14th day of study caused significantly higher contractions compared to the non treated rats, but after 28 days, ileum contractions decr...eased approximately to the level of contractions in non-treated rats. On the 14th study day, we also recorded increased amplitude of spontaneous ileum contractions, compared to non-treated rats. The application of increasing ACh concentrations caused dose-dependent ileum contractions, without statistically significant differences of median effective concentration (EC50) values in non-treated and treated rats. Tolerance to subchronic DZN administration develops due to various adaptation mechanisms, including the most important one downregulation of nicotinic and muscarinic receptor function.
Keywords:
Diazinon / Subchronic intoxication / EFS / Diaphragm / Ileum / RatsSource:
Toxicology Reports, 2016, 3, 523-530Publisher:
- Elsevier Science Bv, Amsterdam
Funding / projects:
- Management of sustainable farming of organic lamb production as a support to rural development (RS-31085)
- Development of herbal medicines and biocides on the basis of Carvacrol, Thymol and Cinnamaldehyde for use in veterinary medicine, animal husbandry and food production without harmful residues (RS-31087)
DOI: 10.1016/j.toxrep.2016.06.002
ISSN: 2214-7500
PubMed: 28959576
WoS: 000399044300061
Scopus: 2-s2.0-84975508604
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Fakultet veterinarske medicineTY - JOUR AU - Ivanović, Saša AU - Dimitrijević, Blagoje AU - Ćupić, Vitomir AU - Jezdimirović, Milanka AU - Borozan, Sunčica AU - Savić, Mila AU - Savić, Đorđe PY - 2016 UR - https://vet-erinar.vet.bg.ac.rs/handle/123456789/1347 AB - Diazinon (DZN) is an organophosphate insecticide which exerts its effect through the inhibition of acetyl cholinesterase enzyme (AChE). In this work, we studied the development of tolerance to subchronic p.o. administration of DZN in rats, under both in vivo and in vitro conditions. A group of 20 rats (2 groups, n = 10) was administered p.o. the 1/10 of established LD50 DZN (namely 55.87 mg/kg bw) for 28 days. On the 14th and 28th day of study with isolated diaphragm and ileum, we examined the downregulation of nicotinic and muscarinic receptor function through Electrical Field Stimulation (EFS). Maximum contractility of the diaphragm was recorded on the 14th day of the study (25% higher compared to the non-treated rats), while on the 28th day the contractions almost did not differ from the values found in non-treated rats. EFS of isolated ileum on the 14th day of study caused significantly higher contractions compared to the non treated rats, but after 28 days, ileum contractions decreased approximately to the level of contractions in non-treated rats. On the 14th study day, we also recorded increased amplitude of spontaneous ileum contractions, compared to non-treated rats. The application of increasing ACh concentrations caused dose-dependent ileum contractions, without statistically significant differences of median effective concentration (EC50) values in non-treated and treated rats. Tolerance to subchronic DZN administration develops due to various adaptation mechanisms, including the most important one downregulation of nicotinic and muscarinic receptor function. PB - Elsevier Science Bv, Amsterdam T2 - Toxicology Reports T1 - Downregulation of nicotinic and muscarinic receptor function in rats after subchronic exposure to diazinon VL - 3 SP - 523 EP - 530 DO - 10.1016/j.toxrep.2016.06.002 ER -
@article{ author = "Ivanović, Saša and Dimitrijević, Blagoje and Ćupić, Vitomir and Jezdimirović, Milanka and Borozan, Sunčica and Savić, Mila and Savić, Đorđe", year = "2016", abstract = "Diazinon (DZN) is an organophosphate insecticide which exerts its effect through the inhibition of acetyl cholinesterase enzyme (AChE). In this work, we studied the development of tolerance to subchronic p.o. administration of DZN in rats, under both in vivo and in vitro conditions. A group of 20 rats (2 groups, n = 10) was administered p.o. the 1/10 of established LD50 DZN (namely 55.87 mg/kg bw) for 28 days. On the 14th and 28th day of study with isolated diaphragm and ileum, we examined the downregulation of nicotinic and muscarinic receptor function through Electrical Field Stimulation (EFS). Maximum contractility of the diaphragm was recorded on the 14th day of the study (25% higher compared to the non-treated rats), while on the 28th day the contractions almost did not differ from the values found in non-treated rats. EFS of isolated ileum on the 14th day of study caused significantly higher contractions compared to the non treated rats, but after 28 days, ileum contractions decreased approximately to the level of contractions in non-treated rats. On the 14th study day, we also recorded increased amplitude of spontaneous ileum contractions, compared to non-treated rats. The application of increasing ACh concentrations caused dose-dependent ileum contractions, without statistically significant differences of median effective concentration (EC50) values in non-treated and treated rats. Tolerance to subchronic DZN administration develops due to various adaptation mechanisms, including the most important one downregulation of nicotinic and muscarinic receptor function.", publisher = "Elsevier Science Bv, Amsterdam", journal = "Toxicology Reports", title = "Downregulation of nicotinic and muscarinic receptor function in rats after subchronic exposure to diazinon", volume = "3", pages = "523-530", doi = "10.1016/j.toxrep.2016.06.002" }
Ivanović, S., Dimitrijević, B., Ćupić, V., Jezdimirović, M., Borozan, S., Savić, M.,& Savić, Đ.. (2016). Downregulation of nicotinic and muscarinic receptor function in rats after subchronic exposure to diazinon. in Toxicology Reports Elsevier Science Bv, Amsterdam., 3, 523-530. https://doi.org/10.1016/j.toxrep.2016.06.002
Ivanović S, Dimitrijević B, Ćupić V, Jezdimirović M, Borozan S, Savić M, Savić Đ. Downregulation of nicotinic and muscarinic receptor function in rats after subchronic exposure to diazinon. in Toxicology Reports. 2016;3:523-530. doi:10.1016/j.toxrep.2016.06.002 .
Ivanović, Saša, Dimitrijević, Blagoje, Ćupić, Vitomir, Jezdimirović, Milanka, Borozan, Sunčica, Savić, Mila, Savić, Đorđe, "Downregulation of nicotinic and muscarinic receptor function in rats after subchronic exposure to diazinon" in Toxicology Reports, 3 (2016):523-530, https://doi.org/10.1016/j.toxrep.2016.06.002 . .