TY - JOUR
T1 - Affinin and hexahydroaffinin
T2 - Chemistry and toxicological profile
AU - de la Rosa-Lugo, Vianey
AU - Déciga-Campos, Myrna
AU - Ríos, María Yolanda
AU - Navarrete-Herrera, Diana Saray
AU - López-Muñoz, Francisco Javier
N1 - Publisher Copyright:
© 2020 Wiley Periodicals, LLC.
PY - 2020/12
Y1 - 2020/12
N2 - The present work aimed to determine the safety parameters of two new alkamides, affinin and hexahydroaffinin, with antinociceptive activity. To predict the preliminary acute toxicity, we used the acute and subchronic toxicity (50 mg/kg, orally [po]) in Swiss Webster mice. Genotoxicity assayed via analysis of cell micronuclei of the femoral bone marrow in mice; at the same time, metabolic parameters determined from peripheral blood samples. Furthermore, to discard the neuropharmacological effects, we assessed the ambulatory activity in mice to determine the possible effects in the central nervous system. Finally, we used capsaicin as a positive control of alkamides. According to our results, hexahydroaffinin (LD50 ≥ 5,000 mg/kg, po) is significantly less noxious than affinin (LD50 = 1,442.2 mg/kg, po) or capsaicin (LD50 = 489.9 mg/kg, po). In subchronic administration, we did not observe any changes in hematological or biochemical parameters in any compound analyzed from peripheral blood samples. Finally, the data from the genotoxicity assay showed micronuclei formation in 28%, 5%, and 3% of mice in the capsaicin, affinin, and hexahydroaffinin groups, respectively. With the results obtained in the present investigation, we suggest that affinin and hexahydroaffinin are not only useful candidates for possible new drugs but also safe compounds.
AB - The present work aimed to determine the safety parameters of two new alkamides, affinin and hexahydroaffinin, with antinociceptive activity. To predict the preliminary acute toxicity, we used the acute and subchronic toxicity (50 mg/kg, orally [po]) in Swiss Webster mice. Genotoxicity assayed via analysis of cell micronuclei of the femoral bone marrow in mice; at the same time, metabolic parameters determined from peripheral blood samples. Furthermore, to discard the neuropharmacological effects, we assessed the ambulatory activity in mice to determine the possible effects in the central nervous system. Finally, we used capsaicin as a positive control of alkamides. According to our results, hexahydroaffinin (LD50 ≥ 5,000 mg/kg, po) is significantly less noxious than affinin (LD50 = 1,442.2 mg/kg, po) or capsaicin (LD50 = 489.9 mg/kg, po). In subchronic administration, we did not observe any changes in hematological or biochemical parameters in any compound analyzed from peripheral blood samples. Finally, the data from the genotoxicity assay showed micronuclei formation in 28%, 5%, and 3% of mice in the capsaicin, affinin, and hexahydroaffinin groups, respectively. With the results obtained in the present investigation, we suggest that affinin and hexahydroaffinin are not only useful candidates for possible new drugs but also safe compounds.
KW - affinin
KW - alkamides
KW - capsaicin
KW - hexahydroaffinin
KW - lethal dose
UR - http://www.scopus.com/inward/record.url?scp=85087571236&partnerID=8YFLogxK
U2 - 10.1002/ddr.21712
DO - 10.1002/ddr.21712
M3 - Artículo
C2 - 33034908
SN - 0272-4391
VL - 81
SP - 969
EP - 977
JO - Drug Development Research
JF - Drug Development Research
IS - 8
ER -