Melatonin protects against tenofovir-induced nephrotoxicity in rats by targeting multiple cellular pathways
| Autor: | Premila Abraham, Hemalatha Ramamoorthy, Bina Isaac |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Antioxidant Side effect Health Toxicology and Mutagenesis Poly ADP ribose polymerase medicine.medical_treatment HIV Infections Pharmacology Toxicology medicine.disease_cause Antiviral Agents Nephrotoxicity Melatonin 03 medical and health sciences 0302 clinical medicine Hepatitis B Chronic medicine Animals Humans Renal Insufficiency Tenofovir Reverse-transcriptase inhibitor business.industry General Medicine Rats 030104 developmental biology Apoptosis Models Animal business 030217 neurology & neurosurgery Oxidative stress Metabolic Networks and Pathways medicine.drug |
| Zdroj: | Humanexperimental toxicology. 40(5) |
| ISSN: | 1477-0903 |
| Popis: | Nephrotoxicity is a dose-limiting side effect of long-term use of tenofovir, a reverse transcriptase inhibitor that is used for the treatment of HIV infection and chronic hepatitis B infection. Identifying an agent that prevents tenofovir disoproxil fumarate (TDF)-induced renal injury can lead to its better tolerance, and a more effective treatment can be achieved. The present study is aimed at investigating whether melatonin, a potent antioxidant and anti-inflammatory agent, protects against TDF nephrotoxicity in rats and to determine its cellular targets. Rats were divided into groups and treated as follows. Group I (control): Rats in this group (n = 6) received sterile water only by gavage for 35 days. Group II: Rats (n = 6) in this group received 600 mg/kg body weight TDF in sterile water by gavage for 35 days. Group III: Rats (n = 6) in this group received once daily 20 mg/kg bodyweight melatonin i.p. 2 h before the administration of 600 mg/kg body weight TDF in sterile water by gavage for 35 days. Group IV: Rats were pretreated daily with 20 mg/kg body weight melatonin i.p. 2 h before the administration of sterile water by gavage. All the rats were sacrificed on the 36th day, after overnight fast. Melatonin pretreatment protected the rats against TDF nephrotoxicity both histologically and biochemically. Biochemically, melatonin pretreatment attenuated TDF-induced, oxidative stress, nitrosative stress, mitochondrial pathway of apoptosis, PARP overactivation and preserved proximal tubular function (p < 0.01). This suggests that melatonin may be useful in ameliorating TDF nephrotoxicity. |
| Databáze: | OpenAIRE |
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