N,N'-diacetylcystine ameliorates inflammation in experimental non-alcoholic steatohepatitis by regulating nuclear transcription factor kappa B activation.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases worldwide that has been continuously increasing recently. NAFLD embraces a spectrum of liver histological alterations, ranging from simple steatosis (NAFL) to severe non-alcoholic steatohepatitis (NASH), that is characterized by fat accumulation, lobular inflammation, and ballooning degeneration in the hepatocytes in the absence of alcohol abuse. The innate immune system has an important role in NASH pathogenesis. Among the components of innate immunity, the nuclear factor kappa B (NF-κB) has been closely associated with NASH. N,N'-diacetylcystine (DiNAC), the disulfide dimer of N-acetylcysteine (NAC), is a potent modulator of the immune system. Previous research has confirmed that DiNAC has beneficial effects in liver injury. In this study, we aimed to investigate the effects of DiNAC on high fat diet (HFD)-induced NASH in rats. Male Sprague-Dawley rats were fed with HFD to produce the NASH model and treated with or without DiNAC for 8 weeks. We assessed serum levels of alanine-aminotransferase (ALT), aspartate aminotransferase (AST), inflammatory cytokines, liver histology, and the expression of NF-κB genes in the liver. The results showed that the levels of ALT and AST were significantly increased in the HFD rat model. DiNAC treatment also resulted in a statistically significant reduction of the levels of ALT and AST. Hematoxylin and eosin (H&E) staining revealed that DiNAC alleviated histological injury. Moreover, DiNAC strongly reduced the generation of inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and interleukin-1ß (IL-1ß), through NF-κB downregulation. Taken together, these results indicate that DiNAC treatment effectively delayed the progression of NASH by suppressing the expression of NF-κB mRNA in the liver. Our data suggest that DiNAC protects liver injury in HFD-treated NASH rats, which might be a promising drug for the treatment of NASH.

N-acetylcysteine protects against liver injure induced by carbon tetrachloride via activation of the Nrf2/HO-1 pathway.

Chronic liver injury is an important clinical problem which eventually leads to cirrhosis, hepatocellular carcinoma and end-stage liver failure. It is well known that cell damage induced by reactive oxygen species (ROS) is an important mechanism of hepatocyte injure. N-acetylcysteine (NAC), a precursor of glutathione (GSH), is well-known role as the antidote to acetaminophen toxicity in clinic. NAC is now being utilized more widely in the clinical setting for non-acetaminophen (APAP) related causes of liver injure. However, the mechanisms underlying its beneficial effects are poorly defined. Thus, Aim of the present study was to investigate potential hepatic protective role of NAC and to delineate its mechanism of action against carbon tetrachloride (CCl4)-induced liver injury in models of rat. Our results showed that the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as malondialdehyde (MDA) contents decreased significantly in CCl4-induced rats with NAC treatment. GSH content and superoxide dismutase (SOD) activities remarkably increased in the NAC groups compared with those in CCl4-induced group. Treatment with NAC had been shown to an increase in nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA levels. In conclusion, these results suggested that NAC upregulated HO-1 through the activation of Nrf2 pathway and protected rat against CCl4-induced liver injure. The results of this study provided pharmacological evidence to support the clinical application of NAC.

Protective effects of N-acetylcysteine on cisplatin-induced oxidative stress and DNA damage in HepG2 cells.

Hepatocyte injury is a common pathological effect of cisplatin (CDDP) in various solid tumor therapies. Thus, strategies for minimizing CDDP toxicity are of great clinical interest. N-acetylcysteine (NAC), a known antioxidant, is often used as an antidote for acetaminophen overdose in the clinic due to its ability to increase the levels of glutathione (GSH). In the present study, the aim was to investigate the protective effects of NAC against CDDP-induced apoptosis in human-derived HepG2 cells. The results showed that upon exposure of the cells to CDDP, oxidative stress was significantly induced. DNA damage caused by CDDP was associated with cell apoptosis. NAC pre-treatment significantly reduced the malondialdehyde (MDA) levels and ameliorated the GSH modulation induced by CDDP. NAC also protected against DNA damage and cell apoptosis. These data suggest the protective role of NAC against hepatocyte apoptosis induced by CDDP was achieved through the inhibition of DNA damage and alterations of the redox status in human derived HepG2 cells. These results indicate that NAC administration may protect against CDDP-induced damage.

Clinical application of magnetic resonance imaging in preoperative evaluation of endometrial cancer.

OBJECTIVE: To investigate the value of magnetic resonance imaging (MRI) in the preoperative assessment of endometrial cancer. METHODS: Ninety-four patients with histopathologically confirmed endometrial carcinoma were retrospectively enrolled in this study. MRI findings were compared with the pathologic findings in all cases. The depth of myometrial invasion and lymph node metastasis were evaluated by T2 weighted imaging (T2WI) combined with contrast enhancement or diffusion weighted imaging (DWI). RESULTS: Among these 94 patients,62 had no or superficial myometrial involvement and 32 cases had deep myometrial involvement. Meanwhile, 24 groups of metastatic lymph nodes and 164 groups of non-metastatic lymph nodes were detected. The accuracy, specificity, sensitivity, negative predictive value, and positive predictive value of T2WI combined with contrast enhancement in discriminating no/superficial myometrial involvement from deep myometrial involvement were 88.3%, 90.3%, 84.4%, 91.8%, and 81.8%, whereas those of T2WI combined with DWI were 81.9%, 87.1%, 71.9%, 85.7%, and 74.2%, respectively. The accuracy, specificity, sensitivity, negative predictive value, and positive predictive value of T2WI combined with contrast enhancement in identifying metastatic lymph nodes were 89.4%, 96.8%, 54.5%, 90.9%, and 78.3%, whereas those of T2WI combined with DWI were 91.5%, 95.5%, 72.7%, 94.3%, and 77.4%, respectively. CONCLUSIONS: T2WI combined with contrast enhancement is superior to T2WI combined with DWI in evaluation of the depth of myometrial invasion. However, DWI is more sensitive in identifying lymph node metastasis than T2WI combined with contrast enhancement.