PubMed · 9509054
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H Swanton. Amiodarone.. https://pubmed.ncbi.nlm.nih.gov/9509054/
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BACKGROUND: Oxidative stress plays an important role in the pathophysiology of ischemic heart disease and heart failure, and antioxidants might be beneficial in the treatment of these patients. This study was performed to determine the scavenging effects of amiodarone on oxygen free radicals and its protective effects against oxygen radical-mediated injury in cardiac myocytes. METHODS AND RESULTS: The formation of the radical spin adduct with hydroxy radical (.OH) in the presence of H(2)O(2) (10 mmol/L) and Fe(3+)-nitrilotriacetate (20 micromol/L) was monitored by electron paramagnetic resonance spectroscopy combined with a spin trapping agent, 5,5-dimethyl pyrroline-N-oxide (DMPO). Amiodarone decreased the intensity of the DMPO-OH signals in a dose-dependent manner (0.1 to 100 micromol/L), whereas other antiarrhythmia drugs such as disopyramide and atenolol had no such effects. Furthermore, amiodarone (10 micromol/L) protected intact adult canine cardiac myocytes against.OH-mediated myocyte injury, as assessed by the degree of morphological change from rod shape to the irreversible hypercontracture state during the exposure of cells to H(2)O(2) and Fe(3+) in vitro. CONCLUSIONS: Amiodarone can protect cardiac myocytes against oxidative stress-mediated injury by directly scavenging oxygen free radicals. Antioxidant action of amiodarone might potentially contribute to the beneficial effects of this drug in the treatment of patients with ischemic heart disease and congestive heart failure.
Amiodarone (AM) is a potent antidysrhythmic agent that is limited in clinical use by its adverse effects, including potentially life-threatening AM-induced pulmonary toxicity (AIPT). The present study tested the ability of dietary supplementation with vitamin E (500 IU d,1-alpha-tocopherol acetate/kg chow) to protect against pulmonary damage following intratracheal administration of AM (1.83 micromol) to the male golden Syrian hamster. At 21 days post-dosing, animals treated with AM had increased lung hydroxyproline content and histological disease index values compared to control (P < 0.05), which were indicative of fibrosis. Dietary vitamin E supplementation for 6 weeks resulted in a 234% increase in lung vitamin E content at the time of AM dosing, and maintenance on the diet prevented AM-induced elevation of hydroxyproline content and disease index 21 days post-dosing. Dietary vitamin E supplementation also decreased hydroxyproline content and disease index values in hamsters treated intratracheally with distilled water, the AM vehicle. These results demonstrate a protective role for vitamin E in an in vivo model of AIPT, and suggest that this antioxidant may have non-specific antifibrotic effects in the lung.
OBJECTIVE: Assess the efficacy of intratumoral chemotherapy in a colonic tumor model implanted subcutaneously in the BD IX rat. METHOD: In order to determine their antitumoral effect, 5 anticancer drugs were administered via intravenous and direct intratumoral routes 2 or 10 days after subcutaneous inoculation of tumoral cells. Intratumoral diffusion was evaluated using Patent blue injected directly into the tumoral tissue. Cisplatinum was administered via intratumoral, intravenous and intra-arterial routes to determine the intratumoral and intrarenal concentrations achieved with each of these administration routes. Cisplatinum was also administered via intravenous and intratumoral infusion for 30 minutes to determine the antitumoral effect of each of these routes. RESULTS: Mitomycin and cisplatinum inhibited growth of tumors which had not yet become established and caused advanced stage tumors to regress. For early stage tumors, the intratumoral route was always more effective than the intravenous route. Patent blue diffusion demonstrated a nonhomogeneous intratumoral distribution. Compared with intravenous or intra-arterial infusion, intratumoral infusion gave much higher concentrations of cisplatinum within the tumors and reduced systemic diffusion. At 7 weeks, the antitumoral effect was equivalent for the 2 administration routes while at 13 weeks, the intratumoral treatment was more effective than the intravenous treatment. CONCLUSION: These findings in an experimental animal model demonstrate that intratumoral chemotherapy is more effective than intravenous chemotherapy. It is however still impossible to consistently cure tumors induced in animals.