Changes in tissue gadolinium biodistribution measured in an animal model exposed to four chelating agents.

PURPOSE: This study investigated the potential to reduce gadolinium levels in rodents after repetitive IV Gadodiamide administration using several chelating agents. MATERIALS AND METHODS: The following six groups of rats were studied. Group 1: Control; Group 2: Gadodiamide only; Group 3: Meso-2,3-Dimercaptosuccinic acid (DMSA) + Gadodiamide; Group 4: N-Acetyl-L-cysteine (NAC) + Gadodiamide; Group 5: Coriandrum sativum extract + Gadodiamide; and Group 6: Deferoxamine + Gadodiamide. Brain, kidney, and blood samples were evaluated via inductively coupled plasma mass spectrometry. The brain was also evaluated histologically. RESULTS: Kidney gadolinium levels in Groups 4 and 5 were approximately double that of Group 2 (p = 0.033 for each). There was almost no calcification in rat hippocampus for Group 4 rodents when compared with Groups 2, 3, 5 and 6. CONCLUSION: Our preliminary study shows that excretion to the kidney has a higher propensity in NAC and Coriandrum sativum groups. It may be possible to change the distribution of gadolinium by administrating several agents. NAC may lower Gadodiamide-induced mineralization in rat hippocampus.

Effect of Ceftiofur on Hyperalgesia and Allodynia in a Rat Neuropathic Pain Model: The Role of Immune Processes.

OBJECTIVE: Inflammatory and immune mechanisms play important roles in the pathogenesis of neuropathic pain. Ceftiofur, a third-generation cephalosporin, has anti-inflammatory effects by inhibiting tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, nuclear factor (NF)-κB, and mitogen-activated protein kinase (MAPK) signaling. This study aimed to investigate the effect of ceftiofur on hyperalgesia and allodynia in neuropathic rats and to define the possible contribution of immune mechanisms to this effect. METHODS: A neuropathic pain model was performed by ligating the right sciatic nerve. Mechanic hyperalgesia and allodynia were measured using an analgesia meter and dynamic plantar esthesiometer, respectively. Following sciatic nerve ligation, ceftiofur was administered intraperitoneally (10 and 20 mg/kg/day) for 14 days. The control group received saline. Pain thresholds were recorded pre- and postoperatively on days 3, 7, 10, and 14. Protein was extracted from lumbar spinal cord tissue on day 14, and TNF-α, IL-1ß, p65 NF-κB, p38 MAPK, and inducible nitric oxide synthase (iNOS) were evaluated by Western blotting. RESULTS: Neuropathic rats showed decreased pain thresholds in analgesia meter and esthesiometer measurements. Ceftiofur 20 mg/kg/day significantly alleviated hyperalgesia, but not allodynia, and the increased iNOS and IL-1ß expression was attenuated in neuropathic rats at both doses while decreasing p38 MAPK expression only at 20 mg/kg/day. TNF-α and p65 NF-κB expression remained unchanged 14 days after surgery. CONCLUSIONS: Ceftiofur has anti-inflammatory effects by decreasing iNOS, IL-1ß, and p38 MAPK expression in lumbar spinal cord, and treatment of neuropathic rats with repeated doses of ceftiofur for 14 days results in antihyperalgesic effects.