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

Abstract

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 non-antioxidative 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), α-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 α-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, α-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, α-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.