Calcitriol Protects against Acetaminophen-Induced Hepatotoxicity in Mice
Acetaminophen (APAP) overdose is one of the major causes of acute liver failure. Severe liver inflammation and the production of oxidative stress occur due to toxic APAP metabolites and glutathione depletion. Growing evidence has proved that vitamin D (VD) exerts anti-inflammatory and antioxidative...
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MDPI AG
2023-05-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/6/1534 |
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| author | Supachaya Sriphoosanaphan Pakkapon Rattanachaisit Kanjana Somanawat Natcha Wanpiyarat Piyawat Komolmit Duangporn Werawatganon |
| author_facet | Supachaya Sriphoosanaphan Pakkapon Rattanachaisit Kanjana Somanawat Natcha Wanpiyarat Piyawat Komolmit Duangporn Werawatganon |
| author_sort | Supachaya Sriphoosanaphan |
| collection | DOAJ |
| description | Acetaminophen (APAP) overdose is one of the major causes of acute liver failure. Severe liver inflammation and the production of oxidative stress occur due to toxic APAP metabolites and glutathione depletion. Growing evidence has proved that vitamin D (VD) exerts anti-inflammatory and antioxidative functions. Our objective was to explore the protective role of calcitriol (VD3) in acute APAP-induced liver injury. <b>Methods</b>: Adult male mice were randomized into three groups; control (n = 8), APAP (n = 8), and VD3 group (n = 8). All mice, except controls, received oral administration of APAP (400 mg/kg) and were sacrificed 24 h later. In the VD3 group, calcitriol (10 µg/kg) was injected intraperitoneally 24 h before and after exposure to APAP. Blood samples were collected to assess serum aminotransferase and inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)]. Liver tissues were analyzed for hepatic glutathione (GSH), malondialdehyde (MDA), and histopathology. <b>Results</b>: APAP administration significantly increased serum aminotransferase, inflammatory cytokines, and induced cellular inflammation and necrosis. APAP also depleted hepatic GSH and elevated oxidative stress, as indicated by high MDA levels. In the APAP group, 25% of the mice (two out of eight) died, while no deaths occurred in the VD3 group. Treatment with calcitriol significantly reduced serum aminotransferase, TNF-α, and IL-6 levels in the VD3 group compared to the APAP group. Additionally, VD3 effectively restored GSH reserves, reduced lipid peroxidation, and attenuated hepatotoxicity. <b>Conclusions</b>: These findings demonstrate that VD3 prevents APAP-induced acute liver injury and reduces mortality in mice through its anti-inflammatory and antioxidative activity. Thus, VD3 might be a novel treatment strategy for APAP-induced hepatotoxicity. |
| first_indexed | 2024-03-11T02:45:05Z |
| format | Article |
| id | doaj.art-c15907d796cc4dab8d862607c27e80bc |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T02:45:05Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-c15907d796cc4dab8d862607c27e80bc2023-11-18T09:24:43ZengMDPI AGBiomedicines2227-90592023-05-01116153410.3390/biomedicines11061534Calcitriol Protects against Acetaminophen-Induced Hepatotoxicity in MiceSupachaya Sriphoosanaphan0Pakkapon Rattanachaisit1Kanjana Somanawat2Natcha Wanpiyarat3Piyawat Komolmit4Duangporn Werawatganon5Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Bangkok 10330, ThailandCenter of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandCenter of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pathology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok 10330, ThailandDivision of Gastroenterology, Department of Medicine, Faculty of Medicine, Bangkok 10330, ThailandCenter of Excellence in Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandAcetaminophen (APAP) overdose is one of the major causes of acute liver failure. Severe liver inflammation and the production of oxidative stress occur due to toxic APAP metabolites and glutathione depletion. Growing evidence has proved that vitamin D (VD) exerts anti-inflammatory and antioxidative functions. Our objective was to explore the protective role of calcitriol (VD3) in acute APAP-induced liver injury. <b>Methods</b>: Adult male mice were randomized into three groups; control (n = 8), APAP (n = 8), and VD3 group (n = 8). All mice, except controls, received oral administration of APAP (400 mg/kg) and were sacrificed 24 h later. In the VD3 group, calcitriol (10 µg/kg) was injected intraperitoneally 24 h before and after exposure to APAP. Blood samples were collected to assess serum aminotransferase and inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)]. Liver tissues were analyzed for hepatic glutathione (GSH), malondialdehyde (MDA), and histopathology. <b>Results</b>: APAP administration significantly increased serum aminotransferase, inflammatory cytokines, and induced cellular inflammation and necrosis. APAP also depleted hepatic GSH and elevated oxidative stress, as indicated by high MDA levels. In the APAP group, 25% of the mice (two out of eight) died, while no deaths occurred in the VD3 group. Treatment with calcitriol significantly reduced serum aminotransferase, TNF-α, and IL-6 levels in the VD3 group compared to the APAP group. Additionally, VD3 effectively restored GSH reserves, reduced lipid peroxidation, and attenuated hepatotoxicity. <b>Conclusions</b>: These findings demonstrate that VD3 prevents APAP-induced acute liver injury and reduces mortality in mice through its anti-inflammatory and antioxidative activity. Thus, VD3 might be a novel treatment strategy for APAP-induced hepatotoxicity.https://www.mdpi.com/2227-9059/11/6/1534vitamin DcalcitriolacetaminophenAPAPhepatotoxicityliver injury |
| spellingShingle | Supachaya Sriphoosanaphan Pakkapon Rattanachaisit Kanjana Somanawat Natcha Wanpiyarat Piyawat Komolmit Duangporn Werawatganon Calcitriol Protects against Acetaminophen-Induced Hepatotoxicity in Mice Biomedicines vitamin D calcitriol acetaminophen APAP hepatotoxicity liver injury |
| title | Calcitriol Protects against Acetaminophen-Induced Hepatotoxicity in Mice |
| title_full | Calcitriol Protects against Acetaminophen-Induced Hepatotoxicity in Mice |
| title_fullStr | Calcitriol Protects against Acetaminophen-Induced Hepatotoxicity in Mice |
| title_full_unstemmed | Calcitriol Protects against Acetaminophen-Induced Hepatotoxicity in Mice |
| title_short | Calcitriol Protects against Acetaminophen-Induced Hepatotoxicity in Mice |
| title_sort | calcitriol protects against acetaminophen induced hepatotoxicity in mice |
| topic | vitamin D calcitriol acetaminophen APAP hepatotoxicity liver injury |
| url | https://www.mdpi.com/2227-9059/11/6/1534 |
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