Anti-inflammatory and antinociceptive effects, and safety toxicological profile of a new paracetamol analog, LQFM291.

Abstract

In the scope of a research program with the goal of developing treatments for inflammatory diseases, the pharmacological evaluation of LQFM291, designed by molecular hybridization from butylated hydroxytoluene and paracetamol, was described. The antioxidant profile of LQFM291 was evaluated by electrochemical measurement. Also, acute or repeated treatments with equimolar doses to paracetamol were used to evaluate the antinociceptive and/or anti-inflammatory activities of LQFM291 in animal models. The toxicologic potential of LQFM291 was also evaluated and compared to paracetamol through biochemical and histopathological analysis after the repeated treatment schedule. As a result of the acute treatment, paracetamol showed a similar antinociceptive effect in formalin test compared to LQFM291. Whereas, after the repeated treatment, when carrageenan-induced hyperalgesia and edema tests were performed, paracetamol showed a delayed antinociceptive and anti-inflammatory effect compared to LQFM291. Furthermore, as other advantages the LQFM291 showed a high redox capacity, a gastroprotective activity and a safety pharmacological profile without any liver or kidney damage. These effects can be related to the prevention of oxidative stress by reduction of protein and lipid peroxidation in gastric tissue, maintenance of glutathione levels in hepatic homogenate, and a systemic reduction of pro-inflammatory cytokine levels, which may characterize the LQFM291 as a more viable and effective alternative to relief pain and inflammatory signs in patients with chronic disorders.

• Authors: Larissa Córdova Turones, Lucas S Machado, Boniek G Vaz, Gerlon de Almeida R Oliveira, Lorrane Kelle da Silva Moreira, Dionys de Souza Almeida, Aline Nazareth Martins, James Oluwagbamigbe Fajemiroye, José Luís R Martins, Paulo César Ghedini, Hericles Mesquita Campos, Fernanda Cristina A Dos Santos, Cinthia Rio Branco da Silva, Luciano M Lião, Eric de Souza Gil, Elson Alves Costa, Ricardo Menegatti
• Journal: Inflammopharmacology (Inflammopharmacology) Vol. 31 Issue 5 Pg. 2451-2465 (Oct 2023) ISSN: 1568-5608 [Electronic] Switzerland
• PMID: 37667090 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Chemical References

• Acetaminophen
• Anti-Inflammatory Agents
• Carrageenan
• Plant Extracts
• Analgesics

Topics

• Animals
• Humans
• Acetaminophen (adverse effects)
• Anti-Inflammatory Agents (therapeutic use)
• Pain (drug therapy)
• Carrageenan
• Plant Extracts (pharmacology)
• Analgesics (adverse effects)
• Edema (chemically induced, drug therapy)