Carnitine in Alleviation of Complications Caused by Acute Valproic Acid Toxicity; an Exprimental Study on Mice
Introduction: Hyperammonemia and hepatotoxicity are well-known complications of valproic acid (VPA) poisoning. The objective of this study is to evaluate the potential role of carnitine in mitigating the adverse effects of acute VPA toxicity in mice. Methods: 54 male mice (25-30 g) were randomly...
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| Format: | Article |
| Language: | English |
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Shahid Beheshti University of Medical Sciences
2023-12-01
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| Series: | Archives of Academic Emergency Medicine |
| Subjects: | |
| Online Access: | https://journals.sbmu.ac.ir/aaem/index.php/AAEM/article/view/2146 |
| _version_ | 1827395782084395008 |
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| author | Akram Jamshidzadeh Reza Heidari Mahdie Shams Melika Ebrahimi-sharghi Sayed Mahdi Marashi |
| author_facet | Akram Jamshidzadeh Reza Heidari Mahdie Shams Melika Ebrahimi-sharghi Sayed Mahdi Marashi |
| author_sort | Akram Jamshidzadeh |
| collection | DOAJ |
| description |
Introduction: Hyperammonemia and hepatotoxicity are well-known complications of valproic acid (VPA) poisoning. The objective of this study is to evaluate the potential role of carnitine in mitigating the adverse effects of acute VPA toxicity in mice.
Methods: 54 male mice (25-30 g) were randomly assigned to one of three categories, including acute, sub-acute, and chronic poisoning. Each category contained 3 groups, each consisting of 6 mice (Group 1: control, Group 2: VPA treated, and Group 3: VPA + carnitine treated). The animals were sacrificed 24 hours after the initial injection, and their blood, liver, and brain samples were compared between groups of each category regarding liver function biomarkers, oxidative stress markers, ammonia level, and liver histopathologic changes using one-way ANOVA followed by Tukey’s multiple comparison test.
Results: The administration of VPA increased the serum level of aspartate aminotransferase (AST) (p=0.003) and alanine aminotransferase (ALT) (p=0.001), as well as serum, and brain level of ammonia (p=0.0001 for both) in the intervention group. Elevated levels of lipid peroxidation and oxidative stress (p=0.0001 for both) in the liver tissue, decreased liver glutathione (p=0.0001) and ferric ion-reducing antioxidant power (FRAP) (p=0.0001), and histopathologic changes in the form of moderate to severe inflammation were observed. Administration of VPA + carnitine reduced AST (p=0.05) and ALT (p=0.01), increased the FRAP, reduced free oxygen radicals and liver lipid peroxidation (p=0.0001 for all), and decreased tissue damage in the form of moderate inflammation. The administration of carnitine was ineffective in reducing brain or plasma ammonia levels in acute VPA-treated animals (p = 0.0115).
Conclusions: Although the administration of carnitine has been suggested as a protective remedy in cases of VPA toxicity, according to the present study, it did not have an antidotal effect and did not prevent encephalopathy or liver injury in acute VPA toxicity.
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| first_indexed | 2024-03-08T18:39:45Z |
| format | Article |
| id | doaj.art-478662745924450cb6e579cda2cbc90e |
| institution | Directory Open Access Journal |
| issn | 2645-4904 |
| language | English |
| last_indexed | 2024-03-08T18:39:45Z |
| publishDate | 2023-12-01 |
| publisher | Shahid Beheshti University of Medical Sciences |
| record_format | Article |
| series | Archives of Academic Emergency Medicine |
| spelling | doaj.art-478662745924450cb6e579cda2cbc90e2023-12-29T08:08:42ZengShahid Beheshti University of Medical SciencesArchives of Academic Emergency Medicine2645-49042023-12-0112110.22037/aaem.v12i1.2146Carnitine in Alleviation of Complications Caused by Acute Valproic Acid Toxicity; an Exprimental Study on MiceAkram Jamshidzadeh0Reza Heidari1Mahdie Shams2Melika Ebrahimi-sharghi3Sayed Mahdi Marashi4aceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, IranPharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, IranStudent Research Committee. Shiraz University of Medical Sciences. Shiraz, IranStudent Research Committee of Pharmacy School. Shiraz University of Medical Sciences. Shiraz, IranAssistant professor of forensic medicine and clinical toxicology, Patient Safety Research Center, Shohadaye Haftom-e-Tir Hospital, Iran University of Medical Sciences, Teharn, Iran. Introduction: Hyperammonemia and hepatotoxicity are well-known complications of valproic acid (VPA) poisoning. The objective of this study is to evaluate the potential role of carnitine in mitigating the adverse effects of acute VPA toxicity in mice. Methods: 54 male mice (25-30 g) were randomly assigned to one of three categories, including acute, sub-acute, and chronic poisoning. Each category contained 3 groups, each consisting of 6 mice (Group 1: control, Group 2: VPA treated, and Group 3: VPA + carnitine treated). The animals were sacrificed 24 hours after the initial injection, and their blood, liver, and brain samples were compared between groups of each category regarding liver function biomarkers, oxidative stress markers, ammonia level, and liver histopathologic changes using one-way ANOVA followed by Tukey’s multiple comparison test. Results: The administration of VPA increased the serum level of aspartate aminotransferase (AST) (p=0.003) and alanine aminotransferase (ALT) (p=0.001), as well as serum, and brain level of ammonia (p=0.0001 for both) in the intervention group. Elevated levels of lipid peroxidation and oxidative stress (p=0.0001 for both) in the liver tissue, decreased liver glutathione (p=0.0001) and ferric ion-reducing antioxidant power (FRAP) (p=0.0001), and histopathologic changes in the form of moderate to severe inflammation were observed. Administration of VPA + carnitine reduced AST (p=0.05) and ALT (p=0.01), increased the FRAP, reduced free oxygen radicals and liver lipid peroxidation (p=0.0001 for all), and decreased tissue damage in the form of moderate inflammation. The administration of carnitine was ineffective in reducing brain or plasma ammonia levels in acute VPA-treated animals (p = 0.0115). Conclusions: Although the administration of carnitine has been suggested as a protective remedy in cases of VPA toxicity, according to the present study, it did not have an antidotal effect and did not prevent encephalopathy or liver injury in acute VPA toxicity. https://journals.sbmu.ac.ir/aaem/index.php/AAEM/article/view/2146Valproic acidChemical and drug induced liver injuryHepatic encephalopathyCarnitine |
| spellingShingle | Akram Jamshidzadeh Reza Heidari Mahdie Shams Melika Ebrahimi-sharghi Sayed Mahdi Marashi Carnitine in Alleviation of Complications Caused by Acute Valproic Acid Toxicity; an Exprimental Study on Mice Archives of Academic Emergency Medicine Valproic acid Chemical and drug induced liver injury Hepatic encephalopathy Carnitine |
| title | Carnitine in Alleviation of Complications Caused by Acute Valproic Acid Toxicity; an Exprimental Study on Mice |
| title_full | Carnitine in Alleviation of Complications Caused by Acute Valproic Acid Toxicity; an Exprimental Study on Mice |
| title_fullStr | Carnitine in Alleviation of Complications Caused by Acute Valproic Acid Toxicity; an Exprimental Study on Mice |
| title_full_unstemmed | Carnitine in Alleviation of Complications Caused by Acute Valproic Acid Toxicity; an Exprimental Study on Mice |
| title_short | Carnitine in Alleviation of Complications Caused by Acute Valproic Acid Toxicity; an Exprimental Study on Mice |
| title_sort | carnitine in alleviation of complications caused by acute valproic acid toxicity an exprimental study on mice |
| topic | Valproic acid Chemical and drug induced liver injury Hepatic encephalopathy Carnitine |
| url | https://journals.sbmu.ac.ir/aaem/index.php/AAEM/article/view/2146 |
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