Alterations in mitochondrial homeostasis in a potassium dichromate model of acute kidney injury and their mitigation by curcumin

Curcumin has protective effects in several acute kidney injury models, including that induced by potassium dichromate (K2Cr2O7). The protective effect of curcumin in this experimental model has been associated to the preservation of mitochondrial bioenergetics. This study is aimed at evaluating whet...

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Veröffentlicht in:Food and chemical toxicology 2020-11, Vol.145, p.111774, Article 111774
Hauptverfasser: Avila-Rojas, Sabino Hazael, Aparicio-Trejo, Omar Emiliano, Briones-Herrera, Alfredo, Medina-Campos, Omar Noel, Reyes-Fermín, Laura María, Martínez-Klimova, Elena, León-Contreras, Juan Carlos, Hernández-Pando, Rogelio, Tapia, Edilia, Pedraza-Chaverri, José
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Sprache:eng
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Zusammenfassung:Curcumin has protective effects in several acute kidney injury models, including that induced by potassium dichromate (K2Cr2O7). The protective effect of curcumin in this experimental model has been associated to the preservation of mitochondrial bioenergetics. This study is aimed at evaluating whether or not curcumin's protective effect in mitochondrial bioenergetics is related to the modulation of mitochondrial dynamics and biogenesis. Wistar rats were treated with a single subcutaneous dose of K2Cr2O7 (12.5 mg/kg) or received curcumin (400 mg/kg/day) by oral gavage 10 days before and one day after the K2Cr2O7 injection. K2Cr2O7 induced kidney dysfunction and increased mitochondrial hydrogen peroxide production, while decreasing the respiration directly attributable to oxidative phosphorylation and mitochondrial membrane potential. In mitochondria, K2Cr2O7 increased fission and reduced fusion. Structural analysis of mitochondria in the proximal tubular cells corroborated their fragmentation and loss of crests' integrity. Regarding mitochondrial biogenesis, K2Cr2O7 decreased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) levels. Conversely, curcumin treatment mitigated the aforementioned alterations and increased the expression of the mitochondrial transcription factor A (TFAM). Taken together, our results suggest that curcumin can protect against renal injury by modulating mitochondrial homeostasis, mitigating alterations in bioenergetics and dynamics, possibly by stimulating mitochondrial biogenesis. [Display omitted] •K2Cr2O7-induced acute kidney injury model is associated with altered mitochondrial homeostasis.•Curcumin mitigates renal mitochondrial dynamics alterations induced by K2Cr2O7.•Curcumin induces mitochondrial biogenesis in K2Cr2O7-induced acute kidney injury model.•Curcumin mitigates mitochondrial uncoupling/depolarization in K2Cr2O7-induced acute kidney injury.
ISSN:0278-6915
1873-6351
DOI:10.1016/j.fct.2020.111774