Protective effects of melatonin and l-carnitine against methotrexate-induced toxicity in isolated rat hepatocytes
| Autor: | Asser I. Ghoneim, Lamiaa A Khatab, Ihab T. Abdel-Raheem |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Antimetabolites Antineoplastic Anti-Inflammatory Agents Apoptosis Pharmacology Antioxidants Nitric oxide Rats Sprague-Dawley Melatonin Lipid peroxidation chemistry.chemical_compound Carnitine medicine Animals General Medicine Glutathione Rats Methotrexate chemistry Toxicity Hepatocytes Trypan blue Chemical and Drug Induced Liver Injury medicine.drug |
| Zdroj: | Naunyn-Schmiedeberg's Archives of Pharmacology. 395:87-97 |
| ISSN: | 1432-1912 0028-1298 |
| DOI: | 10.1007/s00210-021-02176-1 |
| Popis: | The present study was designed to evaluate the possible protective effects of melatonin (MEL) and/or L-carnitine (L-CAR) against methotrexate (MTX)-induced toxicity in isolated rat hepatocytes. Hepatocytes were prepared using collagenase techniques of perfusion and digestion of rat liver. Trypan blue uptake, as well as, glutathione (GSH), lipid peroxidation (LPO), nitric oxide (NO), and tumor necrosis factor-alpha (TNF-α) levels were measured. Caspase-3 activity was also assessed. Pre-incubation of hepatocytes with MEL (1 mM) and/or L-CAR (10 mM) 30 min prior to intoxication with MTX, significantly protected hepatocytes against toxicity. In addition, LPO, NO, TNF-α levels, and caspase-3 activity were decreased in comparison to the MTX-intoxicated group. Furthermore, the two drugs increased the MTX-depleted GSH level. MEL and L-CAR prevented MTX-induced hepatocytotoxicity, at least partly, by their antioxidative, antiinflammatory, and antiapoptotic effects. Further studies are recommended on the clinical pharmacologic and toxicologic effects of MEL and L-CAR in patients receiving MTX. |
| Databáze: | OpenAIRE |
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