Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review
The epidemic of obesity, type 2 diabetes and nonalcoholic liver disease (NAFLD) favors drug consumption, which augments the risk of adverse events including liver injury. For more than 30 years, a series of experimental and clinical investigations reported or suggested that the common pain reliever...
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MDPI AG
2023-01-01
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| Series: | Livers |
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| Online Access: | https://www.mdpi.com/2673-4389/3/1/3 |
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| author | Karima Begriche Clémence Penhoat Pénélope Bernabeu-Gentey Julie Massart Bernard Fromenty |
| author_facet | Karima Begriche Clémence Penhoat Pénélope Bernabeu-Gentey Julie Massart Bernard Fromenty |
| author_sort | Karima Begriche |
| collection | DOAJ |
| description | The epidemic of obesity, type 2 diabetes and nonalcoholic liver disease (NAFLD) favors drug consumption, which augments the risk of adverse events including liver injury. For more than 30 years, a series of experimental and clinical investigations reported or suggested that the common pain reliever acetaminophen (APAP) could be more hepatotoxic in obesity and related metabolic diseases, at least after an overdose. Nonetheless, several investigations did not reproduce these data. This discrepancy might come from the extent of obesity and steatosis, accumulation of specific lipid species, mitochondrial dysfunction and diabetes-related parameters such as ketonemia and hyperglycemia. Among these factors, some of them seem pivotal for the induction of cytochrome P450 2E1 (CYP2E1), which favors the conversion of APAP to the toxic metabolite N-acetyl-<i>p</i>-benzoquinone imine (NAPQI). In contrast, other factors might explain why obesity and NAFLD are not always associated with more frequent or more severe APAP-induced acute hepatotoxicity, such as increased volume of distribution in the body, higher hepatic glucuronidation and reduced CYP3A4 activity. Accordingly, the occurrence and outcome of APAP-induced liver injury in an obese individual with NAFLD would depend on a delicate balance between metabolic factors that augment the generation of NAPQI and others that can mitigate hepatotoxicity. |
| first_indexed | 2024-03-11T06:17:14Z |
| format | Article |
| id | doaj.art-6508eb2fc53a4b0eb0f3910486d485da |
| institution | Directory Open Access Journal |
| issn | 2673-4389 |
| language | English |
| last_indexed | 2024-03-11T06:17:14Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Livers |
| spelling | doaj.art-6508eb2fc53a4b0eb0f3910486d485da2023-11-17T12:13:37ZengMDPI AGLivers2673-43892023-01-0131335310.3390/livers3010003Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical ReviewKarima Begriche0Clémence Penhoat1Pénélope Bernabeu-Gentey2Julie Massart3Bernard Fromenty4INSERM, Univ Rennes, INRAE, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, FranceINSERM, Univ Rennes, INRAE, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, FranceINSERM, Univ Rennes, INRAE, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, FranceINSERM, Univ Rennes, INRAE, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, FranceINSERM, Univ Rennes, INRAE, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, FranceThe epidemic of obesity, type 2 diabetes and nonalcoholic liver disease (NAFLD) favors drug consumption, which augments the risk of adverse events including liver injury. For more than 30 years, a series of experimental and clinical investigations reported or suggested that the common pain reliever acetaminophen (APAP) could be more hepatotoxic in obesity and related metabolic diseases, at least after an overdose. Nonetheless, several investigations did not reproduce these data. This discrepancy might come from the extent of obesity and steatosis, accumulation of specific lipid species, mitochondrial dysfunction and diabetes-related parameters such as ketonemia and hyperglycemia. Among these factors, some of them seem pivotal for the induction of cytochrome P450 2E1 (CYP2E1), which favors the conversion of APAP to the toxic metabolite N-acetyl-<i>p</i>-benzoquinone imine (NAPQI). In contrast, other factors might explain why obesity and NAFLD are not always associated with more frequent or more severe APAP-induced acute hepatotoxicity, such as increased volume of distribution in the body, higher hepatic glucuronidation and reduced CYP3A4 activity. Accordingly, the occurrence and outcome of APAP-induced liver injury in an obese individual with NAFLD would depend on a delicate balance between metabolic factors that augment the generation of NAPQI and others that can mitigate hepatotoxicity.https://www.mdpi.com/2673-4389/3/1/3acetaminophendrug-induced liver injuryobesitynonalcoholic fatty liver diseasesteatosisnonalcoholic steatohepatitis |
| spellingShingle | Karima Begriche Clémence Penhoat Pénélope Bernabeu-Gentey Julie Massart Bernard Fromenty Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review Livers acetaminophen drug-induced liver injury obesity nonalcoholic fatty liver disease steatosis nonalcoholic steatohepatitis |
| title | Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review |
| title_full | Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review |
| title_fullStr | Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review |
| title_full_unstemmed | Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review |
| title_short | Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review |
| title_sort | acetaminophen induced hepatotoxicity in obesity and nonalcoholic fatty liver disease a critical review |
| topic | acetaminophen drug-induced liver injury obesity nonalcoholic fatty liver disease steatosis nonalcoholic steatohepatitis |
| url | https://www.mdpi.com/2673-4389/3/1/3 |
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