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Protective effects of IRFI-042 in monensin induced neurotoxicity in chicks
1Department of Veterinary Public Health, Section of Veterinary Pharmacology and Toxicology, University of Messina, Italy.
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.
Insights
IRFI-042, a vitamin E analogue, protected chicks from monensin neurotoxicity by reducing oxidative stress and lipid peroxidation in the brain. This compound may be a potential therapeutic agent against monensin-induced neuronal damage.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Monensin, an ionophore antibiotic, can cause neuronal cell damage by disrupting ion transport.
- Oxidative stress and lipid peroxidation are implicated in monensin-induced neurotoxicity.
Purpose of the Study:
- To investigate the neuroprotective effects of IRFI-042, a synthetic vitamin E analogue, against monensin toxicity in chicks.
- To determine if IRFI-042 can block lipid peroxidation and mitigate monensin-induced neuronal damage.
Main Methods:
- Monensin toxicity was induced in chicks via oral gavage for 8 days.
- Animals were treated with either IRFI-042 or its vehicle.
- Evaluated survival rate, brain lipid peroxidation, nitric oxide synthase (NOS) mRNA and protein expression, and brain histology.
Main Results:
- Monensin decreased survival, caused behavioral changes, increased brain lipid peroxidation, and altered NOS expression (reduced nNOS, enhanced iNOS).
- IRFI-042 significantly improved survival rates and counteracted monensin-induced oxidative stress and histological changes.
- IRFI-042 administration mitigated monensin's detrimental effects on chick brains.
Conclusions:
- Monensin induces neurotoxicity in chicks through oxidative stress and lipid peroxidation.
- IRFI-042 demonstrates significant neuroprotective potential against monensin-induced neuronal damage.
- IRFI-042 may serve as a valuable therapeutic agent for counteracting neurotoxicity caused by monovalent carboxylic ionophorous polyether antibiotics.
