| 10990116 |
Ariyama J, Shimada H, Aono M, Tsuchida H, Hirai KI: Propofol improves recovery from paraquat acute toxicity in vitro and in vivo. Intensive Care Med. 2000 Jul;26(7):981-7.
OBJECTIVE: To investigate whether the antioxidative sedatives propofol and thiopental can improve recovery from acute paraquat toxicity in A549 cells and in mice. DESIGN: Prospective, controlled, dose-response, in vitro study and prospective, controlled animal study. SETTING: A university animal research laboratory. SUBJECTS: Established human lung cultured cells and male SPF ICR mice. INTERVENTIONS: Paraquat-treated (0.2 mM) A549 cells were incubated either with the antioxidative sedatives propofol (0-0.56 mM) or thiopental (0-2.0 mM), or the nonantioxidative sedatives diazepam (0-3.0 mM), midazolam (0-3.0 mM) and ketamine (0-9.0 mM), as well as the antioxidative drugs, trolox (0-2.0 mM), alpha-tocopherol (0-4.4 mM), antioxidative-processed food (AOB; 0-1.0 mg/ml), superoxide dismutase (SOD; 0 and 3,000 U/ml) and ulinastatin (0 and 50,000 U/ml), for 48 h. Paraquat-treated mice received i.v. injections of 10 mg/kg propofol, 5 mg/kg thiopental, 4.0 mg/kg trolox, 100 mg/kg alpha-tocopherol, 10 mg/kg AOB or 5,000 U/kg SOD, b.i.d. for 4 days (n = 10 each). MEASUREMENTS AND RESULTS: Post-administered propofol and thiopental, as well as the antioxidative drugs, trolox, alpha-tocopherol and AOB, improved A549 cell survival in vitro. The non-antioxidative sedatives SOD and ulinastatin were not protective. An i.p. injection of 50 mg/kg of paraquat resulted in a survival rate of 40% in mice at day 6. Propofol, trolox, alpha-tocopherol and AOB significantly lowered the mortality rate (80% survival), while thiopental did not. CONCLUSION: Post i.v. injection of propofol is protective against paraquat-induced damage. Propofol can be given during mechanical ventilatory support after paraquat poisoning. |
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