Mitochondrial dysfunction and oxidative stress are involved in the mechanism of methotrexate-induced renal injury and electrolytes imbalance - 20/09/18
pages | 7 |
Iconographies | 5 |
Vidéos | 0 |
Autres | 0 |
Graphical abstract |
A schematic representation of the effect of methotrexate-induced mitochondrial dysfunction and oxidative stress in the kidney and its relevance to renal injury and proximal tubular reabsorption defect.
Highlights |
• | Renal injury is a clinical complication associated with methotrexate (MTX) therapy. |
• | MTX-induced renal injury is characterized as tissue damage and serum electrolytes imbalance. |
• | There is no precise mechanism for MTX-induced renal injury. |
• | Mitochondrial dysfunction, energy crisis, and oxidative stress seems to be fundamental mechanisms of MTX nephrotoxicity. |
Abstract |
Methotrexate is a folate analog used against a wide range of diseases including malignancies and autoimmune disorders. On the other hand, clinical use of the MTX is associated with kidney injury and renal failure. There is no clear mechanism for MTX-induced renal injury. The current investigation was designed to evaluate the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of MTX-induced renal injury. Rats received MTX (a single dose of 20 or 30 mg/kg, i.p). Five days after MTX administration, serum biomarkers of kidney injury and tissue markers of oxidative stress were assessed. Moreover, kidney mitochondria were isolated, and several mitochondrial indices were determined. MTX-treated animals developed biochemical evidence of renal injury as judged by elevated serum blood urea nitrogen (BUN), creatinine (Cr) and along with hypokalemia, hypophosphatemia, hypocalcemia, and a decrease in serum glucose, and uric acid. Moreover, MTX caused an increase in kidney reactive oxygen species and lipid peroxidation. Renal glutathione reservoirs were also depleted, and tissue antioxidant capacity was decreased in MTX-treated animals. Kidney histopathological changes including interstitial inflammation, renal tubular degeneration, retraction glomeruli, and vascular congestion were also evident in MTX-treated rats. On the other hand, it was found that mitochondrial parameters including mitochondrial membrane potential, mitochondrial dehydrogenases activity, and mitochondrial glutathione and ATP content were decreased, while lipid peroxidation and mitochondrial permeabilization were increased with MTX treatment. These data suggest a role for mitochondrial dysfunction and oxidative stress in the mechanism of MTX nephrotoxicity.
Le texte complet de cet article est disponible en PDF.Keywords : Cancer chemotherapy, Energy metabolism, Fanconi syndrome, Mitochondria, Oxidative stress
Plan
Vol 107
P. 834-840 - novembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’achat d’article à l’unité est indisponible à l’heure actuelle.
Déjà abonné à cette revue ?