Hepatotoxic Evaluation of <i>N</i>-(2-Hydroxyphenyl)-2-Propylpentanamide: A Novel Derivative of Valproic Acid for the Treatment of Cancer
Valproic acid (VPA) is a drug that has various therapeutic applications; however, it has been associated with liver damage. Furthermore, it is interesting to propose new compounds derived from VPA as <i>N</i>-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA). The HO-AAVPA has better antip...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/17/6282 |
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| author | Ana María Correa Basurto Feliciano Tamay Cach Rosa Adriana Jarillo Luna Laura Cristina Cabrera Pérez José Correa Basurto Fernando García Dolores Jessica Elena Mendieta Wejebe |
| author_facet | Ana María Correa Basurto Feliciano Tamay Cach Rosa Adriana Jarillo Luna Laura Cristina Cabrera Pérez José Correa Basurto Fernando García Dolores Jessica Elena Mendieta Wejebe |
| author_sort | Ana María Correa Basurto |
| collection | DOAJ |
| description | Valproic acid (VPA) is a drug that has various therapeutic applications; however, it has been associated with liver damage. Furthermore, it is interesting to propose new compounds derived from VPA as <i>N</i>-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA). The HO-AAVPA has better antiproliferative activity than the VPA in different cancer cell lines. The purpose of this study was to evaluate the liver injury of HO-AAVPA by acute treatment (once administration) and repeated doses for 7 days under intraperitoneal administration. The median lethal dose value (LD<sub>50</sub>) was determined in rats and mice (females and males) using OECD Guideline 425. In the study, male rats were randomly divided into 4 groups (n = 7), G1: control (without treatment), G2: vehicle, G3: VPA (500 mg/kg), and G4: HO-AAVPA (708 mg/kg, in equimolar ratio to VPA). Some biomarkers related to hepatotoxicity were evaluated. In addition, macroscopic and histological studies were performed. The LD<sub>50</sub> value of HO-AAVPA was greater than 2000 mg/kg. Regarding macroscopy and biochemistry, the HO-AAVPA does not induce liver injury according to the measures of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutathione peroxidase, glutathione reductase, and catalase activities. Comparing the treatment with HO-AAVPA and VPA did not show a significant difference with the control group, while malondialdehyde and glutathione-reduced levels in the group treated with HO-AAVPA were close to those of the control (<i>p</i> ≤ 0.05). The histological study shows that liver lesions caused by HO-AAVPA were less severe compared with VPA. Therefore, it is suggested that HO-AAVPA does not induce hepatotoxicity at therapeutic doses, considering that in the future it could be proposed as an antineoplastic drug. |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T23:17:23Z |
| publishDate | 2023-08-01 |
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| spelling | doaj.art-6a0b360495c849bab05a22b1c19fe4d62023-11-19T08:33:49ZengMDPI AGMolecules1420-30492023-08-012817628210.3390/molecules28176282Hepatotoxic Evaluation of <i>N</i>-(2-Hydroxyphenyl)-2-Propylpentanamide: A Novel Derivative of Valproic Acid for the Treatment of CancerAna María Correa Basurto0Feliciano Tamay Cach1Rosa Adriana Jarillo Luna2Laura Cristina Cabrera Pérez3José Correa Basurto4Fernando García Dolores5Jessica Elena Mendieta Wejebe6Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomas, Ciudad de México 11340, MexicoLaboratorio de Investigación de Bioquímica Aplicada, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomas, Ciudad de México 11340, MexicoLaboratorio de Morfología, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomas, Ciudad de México 11340, MexicoLaboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomas, Ciudad de México 11340, MexicoLaboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomas, Ciudad de México 11340, MexicoLaboratorio de Patología, Instituto de Ciencias Forenses de la Ciudad de México, Av. Niños Héroes 130. Col. Doctores, Delegación Cuauhtémoc, Ciudad de México 06720, MexicoLaboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomas, Ciudad de México 11340, MexicoValproic acid (VPA) is a drug that has various therapeutic applications; however, it has been associated with liver damage. Furthermore, it is interesting to propose new compounds derived from VPA as <i>N</i>-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA). The HO-AAVPA has better antiproliferative activity than the VPA in different cancer cell lines. The purpose of this study was to evaluate the liver injury of HO-AAVPA by acute treatment (once administration) and repeated doses for 7 days under intraperitoneal administration. The median lethal dose value (LD<sub>50</sub>) was determined in rats and mice (females and males) using OECD Guideline 425. In the study, male rats were randomly divided into 4 groups (n = 7), G1: control (without treatment), G2: vehicle, G3: VPA (500 mg/kg), and G4: HO-AAVPA (708 mg/kg, in equimolar ratio to VPA). Some biomarkers related to hepatotoxicity were evaluated. In addition, macroscopic and histological studies were performed. The LD<sub>50</sub> value of HO-AAVPA was greater than 2000 mg/kg. Regarding macroscopy and biochemistry, the HO-AAVPA does not induce liver injury according to the measures of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutathione peroxidase, glutathione reductase, and catalase activities. Comparing the treatment with HO-AAVPA and VPA did not show a significant difference with the control group, while malondialdehyde and glutathione-reduced levels in the group treated with HO-AAVPA were close to those of the control (<i>p</i> ≤ 0.05). The histological study shows that liver lesions caused by HO-AAVPA were less severe compared with VPA. Therefore, it is suggested that HO-AAVPA does not induce hepatotoxicity at therapeutic doses, considering that in the future it could be proposed as an antineoplastic drug.https://www.mdpi.com/1420-3049/28/17/6282acute oral toxicityHO-AAVPAliver injury |
| spellingShingle | Ana María Correa Basurto Feliciano Tamay Cach Rosa Adriana Jarillo Luna Laura Cristina Cabrera Pérez José Correa Basurto Fernando García Dolores Jessica Elena Mendieta Wejebe Hepatotoxic Evaluation of <i>N</i>-(2-Hydroxyphenyl)-2-Propylpentanamide: A Novel Derivative of Valproic Acid for the Treatment of Cancer Molecules acute oral toxicity HO-AAVPA liver injury |
| title | Hepatotoxic Evaluation of <i>N</i>-(2-Hydroxyphenyl)-2-Propylpentanamide: A Novel Derivative of Valproic Acid for the Treatment of Cancer |
| title_full | Hepatotoxic Evaluation of <i>N</i>-(2-Hydroxyphenyl)-2-Propylpentanamide: A Novel Derivative of Valproic Acid for the Treatment of Cancer |
| title_fullStr | Hepatotoxic Evaluation of <i>N</i>-(2-Hydroxyphenyl)-2-Propylpentanamide: A Novel Derivative of Valproic Acid for the Treatment of Cancer |
| title_full_unstemmed | Hepatotoxic Evaluation of <i>N</i>-(2-Hydroxyphenyl)-2-Propylpentanamide: A Novel Derivative of Valproic Acid for the Treatment of Cancer |
| title_short | Hepatotoxic Evaluation of <i>N</i>-(2-Hydroxyphenyl)-2-Propylpentanamide: A Novel Derivative of Valproic Acid for the Treatment of Cancer |
| title_sort | hepatotoxic evaluation of i n i 2 hydroxyphenyl 2 propylpentanamide a novel derivative of valproic acid for the treatment of cancer |
| topic | acute oral toxicity HO-AAVPA liver injury |
| url | https://www.mdpi.com/1420-3049/28/17/6282 |
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