Zinc oxide calcium silicate composite attenuates acute tramadol toxicity in mice

BMC Pharmacol Toxicol. 2023 Feb 9;24(1):9. doi: 10.1186/s40360-023-00647-0.

Abstract

Background: Seizures are considered to be the most common symptom encountered in emergency- rushed tramadol-poisoned patients; accounting for 8% of the drug-induced seizure cases. Although, diazepam clears these seizures, the risk of central respiratory depression cannot be overlooked. Henceforth, three adsorbing composites were examined in a tramadol acute intoxication mouse model.

Methods: Calcium Silicate (Wollastonite) either non-doped or wet doped with iron oxide (3%Fe2O3) or zinc oxide (30% ZnO) were prepared. The composites' adsorption capacity for tramadol was determined in vitro. Tramadol intoxication was induced in Swiss albino mice by a parenteral dose of 120 mg/kg. Proposed treatments were administered within 1 min at 5 increasing doses, i.p. The next 30 min, seizures were monitored as an intoxication symptom. Plasma tramadol concentration was recorded after two hours of administration.

Results: The 3% Fe2O3-containing composite (CSFe3), was found to be composed of mainly wollastonite with very little alpha-hematite. On the other hand, hardystonite and wellimite were developed in the 30%ZnO-containing composite (CSZn3). Micro-round and irregular nano-sized microstructures were established (The particle size of CS was 56 nm, CSFe3 was 49 nm, and CSZn3 was 42 nm). The CSZn3 adsorption capacity reached 1497 mg of tramadol for each gram. Tramadol concentration was reduced in plasma and seizures were inhibited after its administration to mice at three doses.

Conclusion: The calcium silicate composite doped with ZnO presented a good resolution of tramadol-induced seizures accompanied by detoxification of blood, indicating its potential for application in such cases. Further studies are required.

Keywords: Adsorption; Antidote; Nano-microstructure; Silicate phases; Toxicity management; Wollastonite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / adverse effects
  • Animals
  • Calcium Compounds
  • Mice
  • Seizures / chemically induced
  • Seizures / drug therapy
  • Tramadol*
  • Zinc Oxide* / toxicity

Substances

  • Tramadol
  • calcium silicate
  • Zinc Oxide
  • Calcium Compounds
  • Analgesics, Opioid