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.
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The data used to support the findings of this study are available from corresponding author upon request.
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This work count on CAPES, Brazil PhD. study grant support (No. 88882.385886/2019–01) and CNPq, Brazil financial support (No. 306530/2020–1).
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RM designed and synthetized the test compound with the contribution of LSM, BV, GRO, and LML to general chemistry. ESG performed the electrochemical assay. EAC, LCT, and RM assist the experimental design. LCT, EAC, LKM and ANM contributed to execute experimental nociceptive and anti-inflammatory assays. DSA and LKM performed and analyzed the colorimetric cyclooxygenase assay. JLM executed the ulcer index analysis. PCG and HMC realized the biochemical analysis of gastric tissue. LCT, FAS and CBS were involved in the execution of histopathological and immunohistochemical evaluations. All authors revised and approved the final manuscript.
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Turones, L.C., Machado, L.S., Vaz, B.G. et al. Anti-inflammatory and antinociceptive effects, and safety toxicological profile of a new paracetamol analog, LQFM291. Inflammopharmacol 31, 2451–2465 (2023). https://doi.org/10.1007/s10787-023-01324-8
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DOI: https://doi.org/10.1007/s10787-023-01324-8