Alpha-lipoic acid attenuates lipopolysaccharide-induced kidney injury
Clinical and experimental nephrology(2014)
Abstract
Background Kidney is one of the major target organs in sepsis, while effective prevention of septic acute kidney injury has not yet been established. α-Lipoic acid (LA) has been known to exert beneficial effects against lipopolysaccharide (LPS)-induced damages in various organs such as heart, lung, and liver. We investigated the protective effect of LA on LPS-induced kidney injury. Methods Two groups of rats were treated with LPS (20 mg/kg, i.p.), one of which being co-treated with LA (50 mg/kg), while the control group was treated with vehicle alone. Human renal proximal tubular epithelial cells (HK-2 cells) were cultured with or without LPS (10 μg/ml) in the presence or absence of LA (100 μg/ml) for 3 h prior to LPS treatment. Results Serum creatinine level was increased in LPS-treated rats, which was attenuated by LA co-treatment. LPS treatment induced cleaved caspase-3 expression in the kidney, which was counteracted by LA. Terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells increased in the kidneys of LPS-treated rats compared with controls, which was counteracted by LA treatment. Protein expression of inducible nitric oxide synthase and cyclooxygenase-2 detected by immunoblotting and/or immunohistochemical staining, along with mRNA levels of pro-inflammatory cytokines detected by real-time polymerase chain reaction, was increased in the kidney with LPS administration, which was ameliorated with LA treatment. LA also protected LPS-induced tubular dysfunction, preserving type 3 Na + /H + exchanger and aquaporin 2 expressions in the kidney. Suppression of LPS-induced expression of cleaved caspase-3 by LA was also observed in HK-2 cells. Increased protein expression of phospho-extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinases by LPS treatment was attenuated by LA pretreatment, while p38 was not affected by either LPS or LA treatment. MitoTracker Red demonstrated LA prevented LPS-induced increment of mitochondrial oxidative stress, where concurrent 4′,6-diamidino-2-phenylindole staining also revealed marked fragmentation and condensation of nuclei in HK-2 cells treated with LPS, which was prevented by LA. Conclusion LA treatment attenuates LPS-induced kidney injury, such as renal tubular dysfunction, by suppression of apoptosis, and inflammation.
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Key words
Alpha-lipoic acid,Apoptosis,Inflammation,Kidney,Lipopolysaccharide
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