Translocation of heme oxygenase-1 to mitochondria is a novel cytoprotective mechanism against non-steroidal anti-inflammatory drug-induced mitochondrial oxidative stress, apoptosis, and gastric mucosal injury.

A number of diseases that lead to injury of the central nervous system are caused by oxidative stress and inflammation in the brain. In this study, NNMBS275, consisting of the ethanol extract ofViola patrinii, showed potent antioxidative and anti-inflammatory activity in murine hippocampal HT22 cells and BV2 microglia. NNMBS275 increased cellular resistance to oxidative injury caused by glutamate-induced neurotoxicity and reactive oxygen species generation in HT22 cells. In addition, the anti-inflammatory effects of NNMBS275 were demonstrated by the suppression of proinflammatory mediators, including proinflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-αand interleukin-1β). Furthermore, we found that the neuroprotective and anti-inflammatory effects of NNMBS275 were linked to the upregulation of nuclear transcription factor-E2-related factor 2-dependent expression of heme oxygenase-1 in HT22 and BV2 cells. These results suggest that NNMBS275 possesses therapeutic potential against neurodegenerative diseases that are induced by oxidative stress and neuroinflammation.

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Prevention of Nonsteroidal Anti-inflammatory Drug—Induced Gastrointestinal Mucosal Injury

Archives of Internal Medicine ◽

10.1001/archinte.1996.00440190069008 ◽

1996 ◽

Vol 156 (20) ◽

pp. 2321 ◽

Cited By ~ 64

Author(s):

Maurizio Koch

Keyword(s):

Mucosal Injury ◽

Drug Induced ◽

Inflammatory Drug ◽

Anti Inflammatory

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Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. A meta-analysis of randomized controlled clinical trials

Archives of Internal Medicine ◽

10.1001/archinte.156.20.2321 ◽

1996 ◽

Vol 156 (20) ◽

pp. 2321-2332 ◽

Cited By ~ 24

Author(s):

M. Koch

Keyword(s):

Clinical Trials ◽

Meta Analysis ◽

Mucosal Injury ◽

Controlled Clinical Trials ◽

Drug Induced ◽

Inflammatory Drug ◽

Randomized Controlled Clinical Trials ◽

Randomized Controlled ◽

Anti Inflammatory

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Salvianolic Acid C against Acetaminophen-Induced Acute Liver Injury by Attenuating Inflammation, Oxidative Stress, and Apoptosis through Inhibition of the Keap1/Nrf2/HO-1 Signaling

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/9056845 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 10

Author(s):

Chien-Ta Wu ◽

Jeng-Shyan Deng ◽

Wen-Chin Huang ◽

Po-Chou Shieh ◽

Mei-Ing Chung ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Liver Failure ◽

Acute Liver Failure ◽

Heme Oxygenase 1 ◽

Molecular Evidence ◽

Related Factor ◽

Drug Induced ◽

Mitochondrial Oxidative Stress ◽

Salvianolic Acid

Acetaminophen (APAP) overdose is one of the most common causes of drug-induced acute liver failure in humans. To investigate the hepatoprotective effect of salvianolic acid C (SAC) on APAP-induced hepatic damage, SAC was administered by daily intraperitoneal (i.p.) injection for 6 days before the APAP administration in mice. SAC prevented the elevation of serum biochemical parameters and lipid profile including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), and triacylglycerol (TG) against acute liver failure. Additionally, SAC reduced the content of malondialdehyde (MDA), the cytochrome P450 2E1 (CYP2E1), and the histopathological alterations and inhibited the production of proinflammatory cytokines in APAP-induced hepatotoxicity. Importantly, SAC effectively diminished APAP-induced liver injury by inhibiting nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR4), and mitogen-activated protein kinases (MAPKs) activation signaling pathway. Moreover, SAC enhanced the levels of hepatic activities of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in APAP-induced mice. SAC mainly inhibited the activation of apoptotic pathways by reduction of cytochrome c, Bax, and caspase-3 protein expression. Taken together, we provide the molecular evidence that SAC protected the hepatocytes from APAP-induced damage by mitigating mitochondrial oxidative stress, inflammatory response, and caspase-mediated antiapoptotic effect through inhibition of the Keap1/Nrf2/HO-1 signaling axis.

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