Ceftriaxone, a beta-lactam antibiotic, modulates apoptosis pathways and oxidative stress in a rat model of neuropathic pain.

Abstract

PURPOSE:

In our previous study, ceftriaxone, a beta-lactam antibiotic, elicited antinociceptive effects in the chronic constriction injury (CCI) of neuropathic pain. In this study, we assessed apoptosis and oxidative stress in the spinal cord of neuropathic rats treated with ceftriaxone.

METHODS:

45 male Wistar rats were divided as naïve, sham, normal saline-treated CCI rats, and CCI animals treated with the effective dose of ceftriaxone. Involvement of Bax, Bcl2, and caspases 3 and 9, important contributors of programmed cell death (apoptosis), was determined using western blotting at days 3 and 7. The markers of oxidative stress including malondialdehyde (MDA) and reduced glutathione (GSH) were measured on days 3 and 7.

RESULTS:

Increased Bax/Bcl2 ratio and cleaved active forms of caspases 3 and 9 were observed in the spinal cord of CCI rats on day 3. Ceftriaxone attenuated the increased levels of Bax and cleaved forms of caspases 3 and 9, while it increased Bcl2 levels. Bax and active forms of caspases declined by day 7. Consequently, comparison among groups showed no difference at this time. CCI enhanced MDA and decreased GSH on days 3 and 7, while ceftriaxone protected against the CCI-induced oxidative stress.

CONCLUSION:

Our results suggest that ceftriaxone, an upregulator/activator of GLT1, could concomitantly reduce oxidative stress and apoptosis and producing its new analogs lacking antimicrobial activity may represent a novel approach for neuropathic pain treatment.

• Authors: Bahareh Amin, Valiollah Hajhashemi, Khalil Abnous, Hossein Hosseinzadeh
• Journal: BioMed research international (Biomed Res Int) Vol. 2014 Pg. 937568 ( 2014) ISSN: 2314-6141 [Electronic] United States
• PMID: 25028668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Apoptosis Regulatory Proteins
• Malondialdehyde
• Ceftriaxone
• Glutathione

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Ceftriaxone (pharmacology)
• Disease Models, Animal
• Glutathione (metabolism)
• Male
• Malondialdehyde (metabolism)
• Neuralgia (drug therapy, metabolism, pathology)
• Oxidative Stress (drug effects)
• Rats
• Rats, Wistar
• Time Factors