A Boron-Containing Analogue of Acetaminophen Induces Analgesic Effect in Hot Plate Test and Limited Hepatotoxicity
Acetaminophen is the most sold drug to treat pain. The TRPV1 channel is among its main targets. Due to its over-the-counter availability, its use is known as the main cause of acute liver failure induced by drugs. In addition, boron-containing compounds (BCC) have shown higher efficiency, potency, a...
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MDPI AG
2023-06-01
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| Series: | Inorganics |
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| Online Access: | https://www.mdpi.com/2304-6740/11/6/261 |
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| author | Melvin Nadir Rosalez Eunice D. Farfán-García Jesús Badillo-Romero Ricardo Iván Córdova-Chávez José G. Trujillo-Ferrara José A. Morales-González Marvin A. Soriano-Ursúa Marlet Martínez-Archundia |
| author_facet | Melvin Nadir Rosalez Eunice D. Farfán-García Jesús Badillo-Romero Ricardo Iván Córdova-Chávez José G. Trujillo-Ferrara José A. Morales-González Marvin A. Soriano-Ursúa Marlet Martínez-Archundia |
| author_sort | Melvin Nadir Rosalez |
| collection | DOAJ |
| description | Acetaminophen is the most sold drug to treat pain. The TRPV1 channel is among its main targets. Due to its over-the-counter availability, its use is known as the main cause of acute liver failure induced by drugs. In addition, boron-containing compounds (BCC) have shown higher efficiency, potency, and affinity than their carbon counterparts. The present study explored the potential analgesic effect and hepatotoxicity of a BCC with a similar chemical structure to acetaminophen. Docking studies were carried out on the TRPV1 channel. In addition, a hot plate test was carried out with three doses of acetaminophen (APAP) and equimolar doses of 4-acetamidophenylboronic acid (4APB) in C57bl/6 mice. These same mice were submitted to a partial hepatectomy and continued compound administration, then they were sacrificed at day seven of treatment to analyze the liver histology and blood chemistry markers. From the in silico assays, it was observed that APAP and 4APB shared interactions with key residues, but 4APB showed a higher affinity on the orthosteric site. Mice administered with 4APB showed a higher latency time than those administered with their equimolar dose of APAP and the control group, with no motor pathway affected. The 4APB groups did not show an increase in hepatic enzyme activity while the APAP did show an increase in activity that was dose-dependent. Although all the experimental groups did show necrosis and inflammation, all APAP groups showed a greater cellular damage than their 4APB counterparts. In addition, the LD<sub>50</sub> of 4APB is 409 mg/kg (against APAP-LD<sub>50</sub> of 338 mg/kg). Thus, in the current evaluation, 4APB was a better analgesic and safer than APAP. |
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| institution | Directory Open Access Journal |
| issn | 2304-6740 |
| language | English |
| last_indexed | 2024-03-11T02:19:38Z |
| publishDate | 2023-06-01 |
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| record_format | Article |
| series | Inorganics |
| spelling | doaj.art-a6bc56cf6b124aba95a4d78179d8c7d12023-11-18T10:55:29ZengMDPI AGInorganics2304-67402023-06-0111626110.3390/inorganics11060261A Boron-Containing Analogue of Acetaminophen Induces Analgesic Effect in Hot Plate Test and Limited HepatotoxicityMelvin Nadir Rosalez0Eunice D. Farfán-García1Jesús Badillo-Romero2Ricardo Iván Córdova-Chávez3José G. Trujillo-Ferrara4José A. Morales-González5Marvin A. Soriano-Ursúa6Marlet Martínez-Archundia7Academy of Physiology & Postgraduate and Research Section, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis and Diaz Miron S/N, Mexico City 11340, MexicoAcademy of Biochemistry & Postgraduate and Research Section, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis and Diaz Miron S/N, Mexico City 11340, MexicoDepartment of Anatomical Pathology, Hospital General de Zona 2A, Troncoso. Añil 144, Granjas México, Iztacalco, Mexico City 08400, MexicoAcademy of Physiology & Postgraduate and Research Section, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis and Diaz Miron S/N, Mexico City 11340, MexicoAcademy of Biochemistry & Postgraduate and Research Section, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis and Diaz Miron S/N, Mexico City 11340, MexicoLaboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis and Diaz Miron S/N, Mexico City 11340, MexicoAcademy of Physiology & Postgraduate and Research Section, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis and Diaz Miron S/N, Mexico City 11340, MexicoLaboratory for the Design and Development of New Drugs and Biotechnological Innovation, Postgraduate and Research Section, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis and Diaz Miron S/N, Mexico City 11340, MexicoAcetaminophen is the most sold drug to treat pain. The TRPV1 channel is among its main targets. Due to its over-the-counter availability, its use is known as the main cause of acute liver failure induced by drugs. In addition, boron-containing compounds (BCC) have shown higher efficiency, potency, and affinity than their carbon counterparts. The present study explored the potential analgesic effect and hepatotoxicity of a BCC with a similar chemical structure to acetaminophen. Docking studies were carried out on the TRPV1 channel. In addition, a hot plate test was carried out with three doses of acetaminophen (APAP) and equimolar doses of 4-acetamidophenylboronic acid (4APB) in C57bl/6 mice. These same mice were submitted to a partial hepatectomy and continued compound administration, then they were sacrificed at day seven of treatment to analyze the liver histology and blood chemistry markers. From the in silico assays, it was observed that APAP and 4APB shared interactions with key residues, but 4APB showed a higher affinity on the orthosteric site. Mice administered with 4APB showed a higher latency time than those administered with their equimolar dose of APAP and the control group, with no motor pathway affected. The 4APB groups did not show an increase in hepatic enzyme activity while the APAP did show an increase in activity that was dose-dependent. Although all the experimental groups did show necrosis and inflammation, all APAP groups showed a greater cellular damage than their 4APB counterparts. In addition, the LD<sub>50</sub> of 4APB is 409 mg/kg (against APAP-LD<sub>50</sub> of 338 mg/kg). Thus, in the current evaluation, 4APB was a better analgesic and safer than APAP.https://www.mdpi.com/2304-6740/11/6/261acetaminophenboronpainanalgesiaTRPVhepatotoxicity |
| spellingShingle | Melvin Nadir Rosalez Eunice D. Farfán-García Jesús Badillo-Romero Ricardo Iván Córdova-Chávez José G. Trujillo-Ferrara José A. Morales-González Marvin A. Soriano-Ursúa Marlet Martínez-Archundia A Boron-Containing Analogue of Acetaminophen Induces Analgesic Effect in Hot Plate Test and Limited Hepatotoxicity Inorganics acetaminophen boron pain analgesia TRPV hepatotoxicity |
| title | A Boron-Containing Analogue of Acetaminophen Induces Analgesic Effect in Hot Plate Test and Limited Hepatotoxicity |
| title_full | A Boron-Containing Analogue of Acetaminophen Induces Analgesic Effect in Hot Plate Test and Limited Hepatotoxicity |
| title_fullStr | A Boron-Containing Analogue of Acetaminophen Induces Analgesic Effect in Hot Plate Test and Limited Hepatotoxicity |
| title_full_unstemmed | A Boron-Containing Analogue of Acetaminophen Induces Analgesic Effect in Hot Plate Test and Limited Hepatotoxicity |
| title_short | A Boron-Containing Analogue of Acetaminophen Induces Analgesic Effect in Hot Plate Test and Limited Hepatotoxicity |
| title_sort | boron containing analogue of acetaminophen induces analgesic effect in hot plate test and limited hepatotoxicity |
| topic | acetaminophen boron pain analgesia TRPV hepatotoxicity |
| url | https://www.mdpi.com/2304-6740/11/6/261 |
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