ro13-9904 and Reperfusion-Injury

The aim of the present study was to investigate the neuroprotective effect of ceftriaxone in a rat brain ischemia/reperfusion injury model.. The oxidative stress parameter, malondialdehyde (MDA) levels with or without ceftriaxone treatment in brain ischemia/reperfusion injured rats as well as in controls were measured in serum and brain tissue. Motor examinations of the rats were also performed. One-way Analysis of Variance (ANOVA) test was used for analysis. Duncan's Multiple Range Test was performed in multiple comparisons. p < 0.05 were considered statistically significant.  RESULTS: The data of this study showed that ceftriaxone treatment reduced the MDA levels in brain tissues in ischemia/reperfusion injured rats. Moreover, Bederson motor scores were higher in the ceftriaxone treated group as compared to the ischemia group (p = 0.092).. These results suggest that ceftriaxone could be beneficial for the prevention of brain ischemia/reperfusion injury caused by acute arterial occlusion through reducing the tissue MDA level (Tab. 2, Fig. 5, Ref. 24).

Topics: Animals; Brain; Brain Ischemia; Ceftriaxone; Malondialdehyde; Neuroprotective Agents; Oxidative Stress; Rats; Reperfusion Injury

The aim of this study was to investigate the effect of ceftriaxone treatment against short-term global brain ischemia/reperfusion (I/R) injury in rats. The study was carried out on 30 Wistar-albino rats that were divided into three groups: control group (n=10), I/R group (n=10) and I/R-ceftriaxone group (n=10). Malondialdehyde (MDA) levels were significantly increased in the I/R group in comparison with the control group (p<0.001). MDA was significantly lower in the I/R-ceftriaxone group than in the I/R group (p<0.05). Superoxide dismutase activity was significantly decreased in the I/R group and increased in the I/R-ceftriaxone group as compared with the control group. Glutathione peroxidase activity was significantly decreased in the I/R group and increased in the I/R-ceftriaxone group as compared with the I/R group and the control. Histopathologically, ceftriaxone provided morphological improvement compared with the I/R group. We concluded that ceftriaxone has neuron-protective effects due to its antioxidant properties as shown by a decrease in MDA overproduction and histological improvement in brain tissue.

Topics: Animals; Antioxidants; Brain Ischemia; Ceftriaxone; Male; Neuroprotective Agents; Rats; Rats, Wistar; Reperfusion Injury

Recently glutamate transporters have emerged as a potential therapeutic target in a wide range of acute and chronic neurological disorders, owing to their novel mode of action. The modulation of GLT-1, a major glutamate transporter has been shown to exert neuroprotection in various models of ischemic injury and motoneuron degeneration. Therefore, an attempt was made to explore its neuroprotective potential in cerebral ischemia/reperfusion injury using ceftriaxone, a GLT-1 modulator. Pre-treatment with ceftriaxone (100mg/kg. i.v) for five days resulted in a significant reduction (P<0.01) in neurological deficit as well as cerebral infarct volume after 1h of ischemia followed by 24h of reperfusion injury. It also caused a significant (P<0.05) upregulation of GLT-1 mRNA, protein and glutamine synthetase (GS) activity. Furthermore, inhibition of ceftriaxone-mediated increased glutamine synthetase activity by dihydrokainate (DHK), a GLT-1 specific inhibitor, confirms the specific effect of ceftriaxone on GLT-1 activity. In addition, ceftriaxone also induced a significant (P<0.01) increase in [(3)H]-glutamate uptake, mediated by GLT-1 in glial enriched preparation, as evidenced by use of DHK and DL-threo-beta-benzyloxyaspartate (DL-TBOA). Thus, the present study provides overwhelming evidence that modulation of GLT-1 protein expression and activity confers neuroprotection in cerebral ischemia/reperfusion injury.

Topics: Animals; Brain; Brain Ischemia; Ceftriaxone; Cerebral Infarction; Disease Models, Animal; Excitatory Amino Acid Transporter 2; Glutamate-Ammonia Ligase; Glutamic Acid; Kainic Acid; Male; Neuroglia; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Up-Regulation

In patients with infected diabetic foot lesions, and gangrenous, peripheral, occlusive arterial disease, it is important to achieve high concentrations of antibiotics in the tissues, as the extent of amputation is often influenced by the presence of infection. Local transvenous pressure injection of antibiotics, in Bier's arterial arrest, allows high local tissue concentrations to be attained in the extremities. Information on the endothelial compatibility of antibiotics in high concentrations combined with the effect of reperfusion injury following tissue hypoxia is lacking. To evaluate the effect of clindamycin, gentamicin, ceftriaxone and teicoplanin injected in Bier's arterial arrest, on endothelial cells, an in-vitro model using human umbilical venous endothelial cells (HUVEC) has been devised. The intracellular levels of purine nucleotides, reflecting DNA/RNA synthesis, energy production and signal transduction of these cells were measured by means of high-performance liquid chromatography. Incubation of cells with 10 mg/mL clindamycin, gentamicin, ceftriaxone and teicoplanin for 20 min resulted in no significant decline of intracellular purines. Levels of purines obtained after exposure of the cells to 0.1 mmol/L hydrogen peroxide (H2O2), to simulate reperfusion injury, were not significantly different from those obtained from cells allowed to recover after antibiotic exposure. These findings indicate that the infusion of high doses of antibiotics, during Bier's arterial arrest, is compatible with maintenance of endothelial cell function, even in the presence of increased free radical activity, provided the exposure is limited to 20 min.

Topics: Anti-Bacterial Agents; Ceftriaxone; Cells, Cultured; Clindamycin; Endothelium, Vascular; Gentamicins; Humans; Hydrogen Peroxide; Reperfusion Injury; Teicoplanin; Tourniquets; Umbilical Veins