Rajendraparsad Hurchund, Sinegugu E Sibiya, Bernard O Owaga, Peter M O Owira
{"title":"Tenofovir alafenamide compared to tenofovir disoproxil fumarate, induces dysglycemia, and dyslipidemia in Wistar rats.","authors":"Rajendraparsad Hurchund, Sinegugu E Sibiya, Bernard O Owaga, Peter M O Owira","doi":"10.1097/QAD.0000000000003987","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To determine the metabolic effects of tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF) in vivo.</p><p><strong>Design and methods: </strong>Male Wistar rats (Rattus novergicus, 250-300 g body weight) were divided into 3 groups (n = 8) and orally treated daily with 1.0 ml distilled water (group 1), TAF (0.42 mg/kg) (group 2), or TDF (5.0 mg/kg) (group 3), respectively, for 56 days. Glucose tolerance tests were done before the animals were sacrificed by halothane overdose, and blood was collected by cardiac puncture for the analysis of plasma lipids, electrolytes, and insulin. The kidney and pancreatic tissues were excised and homogenized to measure oxidative stress. Compartmentation of TAF and TDF was determined in NRK-52 and Peripheral Blood Mononuclear Cells (PBMC).</p><p><strong>Results: </strong>There were no significant differences in weight gain among controls, TAF- or TDF-treated rats. TAF-treated rats had significantly increased fasting blood glucose (FBG), fasting plasma insulin (FPI), insulin resistance, impaired glucose tolerance, and dyslipidemia compared to control or TDF-treated rats, respectively. There was increased lipid peroxidation in the pancreas of TAF-treated compared to TDF-treated or control animals, respectively. TDF- treated rats presented with symptoms of Fanconi syndrome compared to TAF-treated or control animals, respectively. Kidney homogenates from TDF-treated animals had significantly reduced antioxidant enzyme activity compared to TAF-treated animals or controls, respectively. Intracellular concentrations of TAF were significantly higher than TDF in both NRK-52E cells and PBMC, respectively.</p><p><strong>Conclusions: </strong>TAF treatment is weight-neutral and causes dysglycemia, and dyslipidemia but not Fanconi syndrome compared to TDF.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"AIDS","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/QAD.0000000000003987","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: To determine the metabolic effects of tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF) in vivo.
Design and methods: Male Wistar rats (Rattus novergicus, 250-300 g body weight) were divided into 3 groups (n = 8) and orally treated daily with 1.0 ml distilled water (group 1), TAF (0.42 mg/kg) (group 2), or TDF (5.0 mg/kg) (group 3), respectively, for 56 days. Glucose tolerance tests were done before the animals were sacrificed by halothane overdose, and blood was collected by cardiac puncture for the analysis of plasma lipids, electrolytes, and insulin. The kidney and pancreatic tissues were excised and homogenized to measure oxidative stress. Compartmentation of TAF and TDF was determined in NRK-52 and Peripheral Blood Mononuclear Cells (PBMC).
Results: There were no significant differences in weight gain among controls, TAF- or TDF-treated rats. TAF-treated rats had significantly increased fasting blood glucose (FBG), fasting plasma insulin (FPI), insulin resistance, impaired glucose tolerance, and dyslipidemia compared to control or TDF-treated rats, respectively. There was increased lipid peroxidation in the pancreas of TAF-treated compared to TDF-treated or control animals, respectively. TDF- treated rats presented with symptoms of Fanconi syndrome compared to TAF-treated or control animals, respectively. Kidney homogenates from TDF-treated animals had significantly reduced antioxidant enzyme activity compared to TAF-treated animals or controls, respectively. Intracellular concentrations of TAF were significantly higher than TDF in both NRK-52E cells and PBMC, respectively.
Conclusions: TAF treatment is weight-neutral and causes dysglycemia, and dyslipidemia but not Fanconi syndrome compared to TDF.
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Publishing the very latest ground breaking research on HIV and AIDS. Read by all the top clinicians and researchers, AIDS has the highest impact of all AIDS-related journals. With 18 issues per year, AIDS guarantees the authoritative presentation of significant advances. The Editors, themselves noted international experts who know the demands of your work, are committed to making AIDS the most distinguished and innovative journal in the field. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
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