ABSTRACT
Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.
Subject(s)
Peripheral Nervous System Diseases , Amifostine/therapeutic use , Animals , Antineoplastic Agents/toxicity , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Hyperalgesia/prevention & control , Male , Mice , Oxaliplatin , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/prevention & controlABSTRACT
Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.
Subject(s)
Animals , Male , Rabbits , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/prevention & control , Amifostine/therapeutic use , Oxaliplatin , Hyperalgesia/chemically induced , Hyperalgesia/prevention & control , Hyperalgesia/drug therapy , Antineoplastic Agents/toxicityABSTRACT
A rare case is described of fixed subaortic obstruction due to a prolapsed redundant fibrous septal leaflet of the tricuspid valve, herniated through a membranous ventricular septal defect in a boy aged 11 years. The type of obstruction was not suspected before surgery and there was no shunt through the septal defect. Left ventriculography, was attempted and abandoned due to dangerous arrhythmia. Echocardiogram showed definite fixed subvalvular left ventricular outflow obstruction. Corrective surgery was carried out through aortotomy and right ventriculotomy. Ruptured chordae were resected and the tricuspid valve was replaced into the right ventricle. Redundant fibrous tissue was used to close the septal defect. The postoperative recovery was uneventful after complete AV block in the first 5 days.
