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Protective effects of IRFI-042 in monensin induced neurotoxicity in chicks.
Food Chem Toxicol. 2008 Nov; 46(11):3528-33.FC

Abstract

Monensin, a well known ionophore antibiotic, may cause severe damage in neuronal cells by altering Na+/K+-ATPase and Ca2+-ATPase. We investigated whether IRFI-042, a synthetic analogue of vitamin E, may block lipid peroxidation in neuronal cells and protect against monensin neurotoxicity in chicks. Monensin toxicity was induced in chicks by once-daily administration (150 mg/kg by oral gavages), for 8 days. Sham animals received a saline solution and were used as controls. All animals were randomized to receive either IRFI-042 (20 mg/kg) or its vehicle. Survival rate, brain lipid peroxidation, mRNA for neuronal and inducible nitric oxide synthases (nNOS and iNOS) and brain histological evaluations, including immunohistochemical expression of nNOS and iNOS were performed. Monensin administration decreased survival rate, induced behavioural changes, increased brain lipid peroxidation, reduced brain nNOS mRNA and immunostaining and enhanced iNOS mRNA and immunostaining in the brain in chicks. IRFI-042 significantly improved the survival rate and counteracted monensin-induced changes in chick brains. Our data suggest that monensin is responsible of neurotoxicity in chicks by inducing oxidative stress/lipid peroxidation and that IRFI-042 might represent a useful pharmacological approach to protect against the neuronal damage induced by this monovalent carboxylic ionophorous polyether antibiotic.

Authors+Show Affiliations

Department of Veterinary Public Health, Section of Veterinary Pharmacology and Toxicology, University of Messina, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18834916

Citation

Calò, M, et al. "Protective Effects of IRFI-042 in Monensin Induced Neurotoxicity in Chicks." Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, vol. 46, no. 11, 2008, pp. 3528-33.
Calò M, Marini H, Bitto A, et al. Protective effects of IRFI-042 in monensin induced neurotoxicity in chicks. Food Chem Toxicol. 2008;46(11):3528-33.
Calò, M., Marini, H., Bitto, A., Altavilla, D., Polito, F., Minutoli, L., Lo Cascio, P., Antoci, S., & Squadrito, F. (2008). Protective effects of IRFI-042 in monensin induced neurotoxicity in chicks. Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, 46(11), 3528-33. https://doi.org/10.1016/j.fct.2008.09.009
Calò M, et al. Protective Effects of IRFI-042 in Monensin Induced Neurotoxicity in Chicks. Food Chem Toxicol. 2008;46(11):3528-33. PubMed PMID: 18834916.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of IRFI-042 in monensin induced neurotoxicity in chicks. AU - Calò,M, AU - Marini,H, AU - Bitto,A, AU - Altavilla,D, AU - Polito,F, AU - Minutoli,L, AU - Lo Cascio,P, AU - Antoci,S, AU - Squadrito,F, Y1 - 2008/09/13/ PY - 2008/06/07/received PY - 2008/08/23/revised PY - 2008/09/02/accepted PY - 2008/10/7/pubmed PY - 2009/1/7/medline PY - 2008/10/7/entrez SP - 3528 EP - 33 JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JO - Food Chem Toxicol VL - 46 IS - 11 N2 - Monensin, a well known ionophore antibiotic, may cause severe damage in neuronal cells by altering Na+/K+-ATPase and Ca2+-ATPase. We investigated whether IRFI-042, a synthetic analogue of vitamin E, may block lipid peroxidation in neuronal cells and protect against monensin neurotoxicity in chicks. Monensin toxicity was induced in chicks by once-daily administration (150 mg/kg by oral gavages), for 8 days. Sham animals received a saline solution and were used as controls. All animals were randomized to receive either IRFI-042 (20 mg/kg) or its vehicle. Survival rate, brain lipid peroxidation, mRNA for neuronal and inducible nitric oxide synthases (nNOS and iNOS) and brain histological evaluations, including immunohistochemical expression of nNOS and iNOS were performed. Monensin administration decreased survival rate, induced behavioural changes, increased brain lipid peroxidation, reduced brain nNOS mRNA and immunostaining and enhanced iNOS mRNA and immunostaining in the brain in chicks. IRFI-042 significantly improved the survival rate and counteracted monensin-induced changes in chick brains. Our data suggest that monensin is responsible of neurotoxicity in chicks by inducing oxidative stress/lipid peroxidation and that IRFI-042 might represent a useful pharmacological approach to protect against the neuronal damage induced by this monovalent carboxylic ionophorous polyether antibiotic. SN - 0278-6915 UR - https://www.unboundmedicine.com/medline/citation/18834916/Protective_effects_of_IRFI_042_in_monensin_induced_neurotoxicity_in_chicks_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-6915(08)00482-1 DB - PRIME DP - Unbound Medicine ER -