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Evidence for neurotoxicity associated with amoxicillin in juvenile rats
O Atli1, U Demir-Ozkay2, S Ilgin3
1Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey oatli@anadolu.edu.tr.
Insights
Amoxicillin (AMX) may cause neurotoxicity in children. This study found AMX increased depression-like behaviors and seizure susceptibility in juvenile rats, linked to altered brain chemistry and oxidative stress.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Amoxicillin (AMX) is a widely prescribed antibiotic in children, a demographic at high risk for drug-induced adverse reactions.
- Neurological side effects such as anxiety, hyperactivity, and convulsions have been anecdotally linked to AMX treatment.
Purpose of the Study:
- To investigate the potential neurotoxic effects of clinically relevant amoxicillin doses in female juvenile rats.
- To explore the impact of AMX on behavior, seizure threshold, neurotransmitter levels, and oxidative stress markers in the brain.
Main Methods:
- Female juvenile rats were administered daily oral doses of amoxicillin (25 and 50 mg/kg) for 14 days.
- Behavioral tests (immobility and swimming times) and pentylenetetrazole-induced convulsion tests were performed.
- Brain tissue analysis included measurements of serotonin, glutamate, superoxide dismutase, and catalase levels.
Main Results:
- Amoxicillin administration significantly increased immobility time and decreased swimming time, indicative of depression-like behavior.
- AMX treatment reduced the onset of pentylenetetrazole-induced seizures.
- Significant alterations in neurotransmitters (decreased serotonin, increased glutamate) and reduced antioxidant enzyme activities (superoxide dismutase, catalase) were observed in brain tissues.
Conclusions:
- Amoxicillin administration at clinically relevant doses can induce neurotoxic effects in juvenile rats, including depression-like behaviors and increased seizure susceptibility.
- Altered brain neurotransmitter levels and increased oxidative stress are potential mechanisms underlying AMX-induced neurotoxicity.
- These findings highlight the need for careful monitoring of neurological side effects in children undergoing amoxicillin treatment.
Abstract:
Amoxicillin (AMX) is one of the most commonly prescribed antibiotics for children, and childhood is the period to have the highest risk for toxicity cases including drug-induced adverse reactions. Some neurological adverse effects (anxiety, hyperactivity, confusion, convulsions, and behavioral changes) have been reported related to AMX treatment. In the present study, we aimed to determine the neurotoxic effects of AMX administration at clinically relevant doses in female juvenile rats. AMX was administered in single oral daily doses of 25 and 50 mg/kg for 14 days. According to our results, while AMX administration caused a significant increase in the immobility time of animals, swimming time of these animals significantly decreased. AMX administration significantly reduced the onset of pentylenetetrazole-induced convulsions. The serotonin levels of brain tissues in the AMX-administered groups were decreased significantly, which is thought to be related to depression. The glutamate levels in brain tissues increased significantly in AMX-administered groups, which is thought to be related to convulsion. Otherwise, superoxide dismutase and catalase activities were significantly decreased in brain tissues of AMX-administered groups. In conclusion, AMX administration triggered depression and shortened the time of the appearance of first seizure in juvenile rats. Also, altered brain neurotransmitter levels and increased oxidative stress observed in our study were thought to be the possible underlying mechanisms of AMX-induced neurotoxicity.
