N-acetyl cysteine protects cells from chondrocyte death induced by local anesthetics.

Local anesthetics (LA) are among the drugs most frequently used for musculoskeletal problems, in procedures ranging from diagnosis to postoperative pain control. Chondrocyte toxicity induced by LA is an emerging area of concern. The purpose of this study was to determine whether N-acetyl cysteine (NAC), an antioxidant, will exert cytoprotective effects against chondrocyte death induced by LA. Primary cultured human chondrocytes were used for this study. This study used control, NAC, LA, and NAC-LA groups. Cytotoxicity was induced in the LA subgroups and their paired NAC-LA subgroups through exposure to ropivacaine (0.075%), bupivacaine (0.05%), or lidocaine (0.2%) for 24 h. The NAC-LA subgroups were exposed to 10 mM NAC for 1 h, before LA exposure. These study groups were evaluated for rates of cell viability, apoptosis, necrosis, intracellular ROS production, and caspase-3/7 activity. Cell viability in all LA subgroups was significantly lower than in the control group (p < 0.001). Cell viability in the NAC-LA subgroups was significantly higher than in their paired LA subgroups (p < 0.001). In the LA subgroups, rates of apoptosis and necrosis, intracellular ROS production, and caspase-3/7 activity were significantly higher than in the control group (p ≤ 0.029). In the NAC-LA subgroups, rates of apoptosis and necrosis, intracellular ROS production, and caspase-3/7 activity were significantly lower than in their paired LA subgroups (p ≤ 0.023). These results indicate that N-acetyl cysteine, an antioxidant, has cytoprotective effects against LA-induced toxicity to chondrocytes in vitro. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:297-303, 2017.

Comparison of Anti-Oxidant and Anti-Inflammatory Effects between Fresh and Aged Black Garlic Extracts.

Numerous studies have demonstrated that aged black garlic (ABG) has strong anti-oxidant activity. Little is known however regarding the anti-inflammatory activity of ABG. This study was performed to identify and compare the anti-oxidant and anti-inflammatory effects of ABG extract (ABGE) with those of fresh raw garlic (FRG) extract (FRGE). In addition, we investigated which components are responsible for the observed effects. Hydrogen peroxide (H2O2) and lipopolysaccharide (LPS) were used as a pro-oxidant and pro-inflammatory stressor, respectively. ABGE showed high ABTS and DPPH radical scavenging activities and low ROS generation in RAW264.7 cells compared with FRGE. However, inhibition of cyclooxygenase-2 and 5-lipooxygenase activities by FRGE was stronger than that by ABGE. FRGE reduced PGE2, NO, IL-6, IL-1ß, LTD4, and LTE4 production in LPS-activated RAW264.7 cells more than did ABGE. The combination of FRGE and sugar (galactose, glucose, fructose, or sucrose), which is more abundant in ABGE than in FRGE, decreased the anti-inflammatory activity compared with FRGE. FRGE-induced inhibition of NF-κB activation and pro-inflammatory gene expression was blocked by combination with sugars. The lower anti-inflammatory activity in ABGE than FRGE could result from the presence of sugars. Our results suggest that ABGE might be helpful for the treatment of diseases mediated predominantly by ROS.

Antioxidant's cytoprotective effects on rotator cuff tenofibroblasts exposed to aminoamide local anesthetics.

Local anesthetics (LA) are among the drugs most frequently used for musculoskeletal problems, in procedures ranging from diagnosis to postoperative pain control. The cytotoxicity of LA is an emerging area of concern. The purpose of this study was to determine whether cyanidin, an antioxidant, exerts cytoprotective effects against tenofibroblast death induced by LA. Primary cultured human rotator cuff tenofibroblasts were used to evaluate the cytotoxicity of these LA: Ropivacaine (0.075%), Bupivacaine (0.05%), and Lidocaine (0.2%). The effects of cyanidin (100 µg/ml) on the cytotoxicity induced by these LA were investigated. Cell viability, ROS production, caspase-3/7 activity, and expressions of phospho-extracellular signal-regulated kinases (ERK), phospho-p38, phospho-c-Jun N-terminal kinase (JNK), and cleaved PARP-1 were evaluated. Exposure to LA significantly induced cell death (p < 0.001), ROS production (p ≤ 0.04), the activation of caspase-3/7 (p < 0.001), and the increased expressions of phospho-ERK, phospho-p38, phospho-JNK, and cleaved PARP-1. These LA-induced cytotoxic effects were reduced by cyanidin. These data indicate that cyanidin, an antioxidant, has cytoprotective effects against LA-induced cytotoxicity to rotator cuff tenofibroblasts.