Adjuvant Effect Of Antioxidants On Propofol Or Etomidate Anesthesia In Mice

Objective:To reduce the amount of narcotic drugs, one of the common methods is combination of different adjuvant anesthetic drugs. Many anesthetic agents, not just propofol, are both "anesthetic" and "antioxidant". To prove whether and how antioxidants affect the dose of general anesthetics in vivo. And still produce similar pharmacological effects to get a satisfactory sedation.Methods:Clinically wide applications of propofol and etomidate were selected as our general anesthetic drugs, and Vitamin C(Vc), Glutathione(GSH), N-acetylcysteine(NAC) and Edaravone commonly used as the clinical representatives of antioxidant agents. These four antioxidants, as preoperative medication in advance or a adjuvant anesthetic drugs at the same time, were given to mice to determine dosage thresholds of entering the hypnotic state (loss of righting reflex) by propofol, etomidate, and anti-oxidants+propofol/etomidate. Take propofol and Vitamin C as examples, three end-points were used to assess the general anesthetic componets:the loss of righting reflex (LORR; as a measure of unconsciousness), tail flick test (as a measure of antinociception) and hemodynamic and rectal temperature parameters changes. In open field test, we observed spontaneous activity change for anti-oxidants and hypnotic drugs in mice.Results:Part1:Four clinical representative kinds of antioxidant drugs as preoperative medication, could be significantly lower PPF or etomidate hypnotic induction dose. The hypnotic induction dose thresholds were similar when Vc, GSH or Edaravone, combined with PPF, Etomidate had been given in prior or at the same time. NAC200mg/kg might decrease the dose of PPF to40mg/kg and the effect of LORR was similar to PPF80mg/kg. Mice were to resemble to the response of the heat stimulus under the equivalent induction threshold dose (PPF80mg/kg&PPF50mg/kg+Vc200mg/kg); The relationship of dose-anesthetic duration between propofol80mg/kg and different dosages of Vc was certain(P<0.05), but not in PPF100mg/kg and different dosages of Vc. In the mathematical analysis of the Vc dose, PPF dose, and hypnotic duration, the non-linear regression equation fitted better, Fitting quadratic equation: Time=-18.3065+0.0112*Vc+0.2294*Propofol-0.0005*Vc2+0.0012*Propofol2+0.0026*Propofol*Vc Adjusted R-squared=0.8206, P<0.001. Vc and PPF showed a significant synergistic effect;Part2:PPF alone or different Vic and PPF cocktails of hypnotic thresholds, did not show significantly different effect on HR, SBP, DBP, MAP, but made the parameters mentioned above lower in comparison with awake animals, NS control group and Vc groups. There was no significant difference in the HR, BP among awake animals, NS control group and Vc groups. And the center temperature at the end of the experiment was not significantly different among all groups. Regardless of PPF dose80mg/kg or100mg/kg, the relationships of different dosages of Vc and PPF were not in dosage dependent way. Sub-anesthetic amount of PPF could shorten TFL, and the effect of hyperalgesia may be reduced since PPF dose increased,; Vc did not noteably affect the response to hot stimulation. Vc, PPF, or Vc and PPF cocktails of hypnotic thresholds could make the animal appear anxiolytic-like behavior performance, that is, reducig total distance within10min, extending static duration and slowing down the movement. And among Vc200mg/kg,100mg/kg and67mg/kg three dose groups, the anxiolytic-like effects were not in concentration dependent way. Anxiolytic-like effect was similar between PPF80mg/kg and Vc200mg/kg combined with PPF50mg/kg.Conclusion:There was adjuvant effect of anti-oxidants on intravenous anesthetics in vivo. When anti-oxidants given, the total narcotic drug dosage itself significantly reduced or the anesthetic duration was longer. A synergistic effect of the combined application was shown between Vc and PPF. The total narcotic drug dosage itself decreased, since a similar degree achieved on the effects of hypnosis, antinociception, cardiovascular parameters and body temperature. Anti-oxidants played an anxiolytic-like effect in the open field test.