Heng Fan1, Jian-Wei Le1, Jian-Hua Zhu2. 1. Department of Intensive Care Unit, Ningbo First Hospital, Ningbo, Zhejiang Province, P.R China. 2. Department of Intensive Care Unit, Ningbo First Hospital, Ningbo, Zhejiang Province, P.R China. Electronic address: zhujianhua201107@163.com.
Abstract
BACKGROUND: The aim of this study is to investigate the protective effect of N-acetylcysteine (NAC) pretreatment on acute kidney injury in septic rats. METHODS: We constructed a septic rat model by cecal ligation and perforation (CLP) and assessed kidney tissue pathologic damage, renal function changes, and inflammatory factor levels. Meanwhile, we also assessed oxide and antioxidant enzyme levels in kidney tissues, observed apoptosis of kidney tissues, and evaluated mitochondrial membrane activity in renal cortical cells. RESULTS: Pretreatment of NAC significantly alleviated pathologic damage of kidney tissues in septic rats; decreased the levels of serum creatinine, blood urea nitrogen, plasma neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1; and reduced the expression of tumor necrosis factor a, interleukin [IL]-1β, IL-6, and IL-8. Furthermore, NAC pretreatment reduced the level of protein-nitrotyrosine adducts and malondialdehyde in CLP-induced kidney tissues, while elevated the levels of superoxide dismutase, glutathione peroxidase, and catalase. Moreover, pretreatment of NAC reduced the number of apoptosis in kidney tissues induced by CLP, decreased the mRNA levels of caspase-3, caspase-9, cytochrome c, and poly ADP-ribose polymerase, and increased mitochondrial membrane activity in renal cortical cells (complex I/II/III/IV). CONCLUSIONS: NAC pretreatment has protective effects on acute kidney injury induced by CLP, and its mechanism is closely related to anti-inflammatory, antioxidation, antiapoptosis, and regulation of mitochondrial function.
BACKGROUND: The aim of this study is to investigate the protective effect of N-acetylcysteine (NAC) pretreatment on acute kidney injury in septic rats. METHODS: We constructed a septic rat model by cecal ligation and perforation (CLP) and assessed kidney tissue pathologic damage, renal function changes, and inflammatory factor levels. Meanwhile, we also assessed oxide and antioxidant enzyme levels in kidney tissues, observed apoptosis of kidney tissues, and evaluated mitochondrial membrane activity in renal cortical cells. RESULTS: Pretreatment of NAC significantly alleviated pathologic damage of kidney tissues in septic rats; decreased the levels of serum creatinine, blood ureanitrogen, plasma neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1; and reduced the expression of tumor necrosis factor a, interleukin [IL]-1β, IL-6, and IL-8. Furthermore, NAC pretreatment reduced the level of protein-nitrotyrosine adducts and malondialdehyde in CLP-induced kidney tissues, while elevated the levels of superoxide dismutase, glutathione peroxidase, and catalase. Moreover, pretreatment of NAC reduced the number of apoptosis in kidney tissues induced by CLP, decreased the mRNA levels of caspase-3, caspase-9, cytochrome c, and poly ADP-ribose polymerase, and increased mitochondrial membrane activity in renal cortical cells (complex I/II/III/IV). CONCLUSIONS:NAC pretreatment has protective effects on acute kidney injury induced by CLP, and its mechanism is closely related to anti-inflammatory, antioxidation, antiapoptosis, and regulation of mitochondrial function.