Magnesium Lithospermate B Protects Against Cisplatin-Induced Acute Kidney Injury via Alleviating Mitochondrial Dysfunction

Abstract

Purpose Apoptosis plays a critical role in cisplatin-induced acute kidney injury (AKI) and is related to mitochondrial dysfunction. Magnesium lithospermate B (Mlb), one of the most important components of Salvia miltiorrhiza Bunge, is mainly used to treat cardiovascular diseases because of its anti-apoptotic effects. The mechanism underlying the protective effect of Mlb against cisplatin-induced AKI remains unclear. In this study, we investigated the protective effect of Mlb on mitochondrial function against apoptosis caused by cisplatin-induced renal injury. Methods Renal injury induced by cisplatin in mouse renal tubular epithelial cells (mTECs) was measured by quantifying serum creatinine levels, mitochondrial morphology, cell viability, apoptosis, Dynamin-related protein 1(Drp1) expression, etc. The cells were then administered Mlb to determine its protective effects against cisplatin-induced AKI. Results Mlb treatment significantly reduced serum creatinine levels and pathological injury of renal, inhibited the production of malondialdehyde, and reduced the depletion of superoxide dismutase. In addition, Mlb reduced Bax/Bcl2, cleaved caspase-3/caspase-3, and maintained mitochondrial integrity after AKI. Mlb administration also improved cell viability and reduced the percentage of apoptotic cells in vitro. Furthermore, Mlb reduced mitochondrial reactive oxygen species, improved mitochondrial membrane potential, and ameliorated mitochondrial morphological abnormalities by downregulating Drp1 expression. Conclusion These results indicated that Mlb could protect the kidneys against cisplatin-induced apoptosis by alleviating mitochondrial dysfunction.

The role of Mitochondrial Fission Proteins in Mitochondrial Dynamics in Kidney Disease

“…Meanwhile, curcumin can target FIS1 and prevent elevation of FIS1 as well as prevent decrease in mitochondrial fusion protein; the protective and preventive role of curcumin in cisplatin-induced AKI cannot be ignored [ 135 ]. Emodin is an anthraquinone derivative that significantly prevents increase in DRP1 expression and, thus, promotes reduced renal cell injury in AKI [ 154 ], and magnesium stigmasterate B plays a similar protective role in AKI by targeting DRP1 to renal cells [ 155 ]. High glucose often causes fragmentation of the mitochondrial network and cell death.…”