Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice
Doxepin is commonly prescribed for depression and anxiety treatment. Doxepin-related disruptions to metabolism and renal/hepatic adverse effects remain unclear; thus, the underlying mechanism of action warrants further research. Here, we investigated how doxepin affects lipid change, glucose homeost...
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| Format: | Article |
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MDPI AG
2021-03-01
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| Online Access: | https://www.mdpi.com/1424-8247/14/3/267 |
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| author | Geng-Ruei Chang Po-Hsun Hou Wei-Cheng Yang Chao-Min Wang Pei-Shan Fan Huei-Jyuan Liao To-Pang Chen |
| author_facet | Geng-Ruei Chang Po-Hsun Hou Wei-Cheng Yang Chao-Min Wang Pei-Shan Fan Huei-Jyuan Liao To-Pang Chen |
| author_sort | Geng-Ruei Chang |
| collection | DOAJ |
| description | Doxepin is commonly prescribed for depression and anxiety treatment. Doxepin-related disruptions to metabolism and renal/hepatic adverse effects remain unclear; thus, the underlying mechanism of action warrants further research. Here, we investigated how doxepin affects lipid change, glucose homeostasis, chromium (Cr) distribution, renal impairment, liver damage, and fatty liver scores in C57BL6/J mice subjected to a high-fat diet and 5 mg/kg/day doxepin treatment for eight weeks. We noted that the treated mice had higher body, kidney, liver, retroperitoneal, and epididymal white adipose tissue weights; serum and liver triglyceride, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine levels; daily food efficiency; and liver lipid regulation marker expression. They also demonstrated exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. The treated mice had a net-negative Cr balance due to increased urinary excretion, leading to Cr mobilization, delaying hyperglycemia recovery. Furthermore, they had considerably increased fatty liver scores, paralleling increases in adiponectin, FASN, PNPLA3, <i>FABP4</i> mRNA, and <i>SREBP1</i> mRNA levels. In conclusion, doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes. |
| first_indexed | 2024-03-10T13:13:07Z |
| format | Article |
| id | doaj.art-fb022dace328450bb2a84341d9c927cb |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T13:13:07Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-fb022dace328450bb2a84341d9c927cb2023-11-21T10:40:02ZengMDPI AGPharmaceuticals1424-82472021-03-0114326710.3390/ph14030267Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese MiceGeng-Ruei Chang0Po-Hsun Hou1Wei-Cheng Yang2Chao-Min Wang3Pei-Shan Fan4Huei-Jyuan Liao5To-Pang Chen6Department of Veterinary Medicine, National Chiayi University, 580 Xinmin Road, Chiayi 60054, TaiwanDepartment of Psychiatry, Taichung Veterans General Hospital, 1650 Taiwan Boulevard (Section 4), Taichung 40705, TaiwanSchool of Veterinary Medicine, National Taiwan University, 1 Roosevelt Road (Section 4), Taipei 10617, TaiwanDepartment of Veterinary Medicine, National Chiayi University, 580 Xinmin Road, Chiayi 60054, TaiwanDepartment of Veterinary Medicine, National Chiayi University, 580 Xinmin Road, Chiayi 60054, TaiwanDepartment of Veterinary Medicine, National Chiayi University, 580 Xinmin Road, Chiayi 60054, TaiwanDivision of Endocrinology and Metabolism, Show Chwan Memorial Hospital, 542 Chung-Shan Road (Section 1), Changhua 50008, TaiwanDoxepin is commonly prescribed for depression and anxiety treatment. Doxepin-related disruptions to metabolism and renal/hepatic adverse effects remain unclear; thus, the underlying mechanism of action warrants further research. Here, we investigated how doxepin affects lipid change, glucose homeostasis, chromium (Cr) distribution, renal impairment, liver damage, and fatty liver scores in C57BL6/J mice subjected to a high-fat diet and 5 mg/kg/day doxepin treatment for eight weeks. We noted that the treated mice had higher body, kidney, liver, retroperitoneal, and epididymal white adipose tissue weights; serum and liver triglyceride, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine levels; daily food efficiency; and liver lipid regulation marker expression. They also demonstrated exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. The treated mice had a net-negative Cr balance due to increased urinary excretion, leading to Cr mobilization, delaying hyperglycemia recovery. Furthermore, they had considerably increased fatty liver scores, paralleling increases in adiponectin, FASN, PNPLA3, <i>FABP4</i> mRNA, and <i>SREBP1</i> mRNA levels. In conclusion, doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.https://www.mdpi.com/1424-8247/14/3/267doxepinobesitychromiumfatty liver diseaserenal impairmentglucose intolerance |
| spellingShingle | Geng-Ruei Chang Po-Hsun Hou Wei-Cheng Yang Chao-Min Wang Pei-Shan Fan Huei-Jyuan Liao To-Pang Chen Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice Pharmaceuticals doxepin obesity chromium fatty liver disease renal impairment glucose intolerance |
| title | Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice |
| title_full | Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice |
| title_fullStr | Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice |
| title_full_unstemmed | Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice |
| title_short | Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice |
| title_sort | doxepin exacerbates renal damage glucose intolerance nonalcoholic fatty liver disease and urinary chromium loss in obese mice |
| topic | doxepin obesity chromium fatty liver disease renal impairment glucose intolerance |
| url | https://www.mdpi.com/1424-8247/14/3/267 |
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