Propofol improves recovery from paraquat acute toxicity in vitro and in vivo.

Abstract

To investigate whether the antioxidative sedatives propofol and thiopental can improve recovery from acute paraquat toxicity in A549 cells and in mice. Prospective, controlled, dose-response, in vitro study and prospective, controlled animal study. A university animal research laboratory. Established human lung cultured cells and male SPF ICR mice. 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). 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. Post i.v. injection of propofol is protective against paraquat-induced damage. Propofol can be given during mechanical ventilatory support after paraquat poisoning.