N-Acetylcysteine Amide (NACA) Reduces Cell Death after Oxidative Stress in a Porcine Embryonic Kidney Cell Line
- 1 Department of Pediatrics, Vestre Viken Hospital Trust, Drammen, Norway
- 2 Department of Pediatric Research, Division of Pediatric and Adolescent Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- 3 Department of Women’s and Children’s Health, Division of Paediatric Endocrinology, Karolinska Institutet, Stockholm, Sweden
- 4 Department of Pediatrics, Vestfold Hospital Trust, Tønsberg, Norway
- 5 Department of Pediatric Research, Division of Pediatric and Adolescent Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- 6 Department of Pediatric Research, Division of Pediatric and Adolescent Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
Abstract
Introduction: Oxidative stress may have detrimental effects on different structures of the cells, such as the DNA. Recently, we have published a study demonstrating that N-Acetylcysteine amide (NACA) displayed anti-inflammatory properties on the brain after exposure to oxidative stress in an established neonatal piglet model, imitating perinatal asphyxia. As different clinical studies have shown an association between the severity of hypoxic-ischemic encephalopathy and damage of the kidneys, we investigated a possible protective effect of NACA against H 2 O 2 -induced oxidative stress using a porcine epithelial-like embryonic kidney cell line (EFN-R). Objective: To investigate a potential protective effect of NACA on cells of a porcine embryonic kidney cell line exposed to H 2 O 2 . Methods: We subjected the cells to different concentrations of H 2 O 2 for variable time periods, seeking the optimal dose-response for the experiments. Based on the results of these investigations, we exposed the cells to 100 μMol of H 2 O 2 and/or 750 μM of NACA for 24 hours. Some of the cells would receive NACA either one hour before or one hour after exposure to H 2 O 2 . Results: The viability of the investigated EFN-R cells revealed that both, the group treated with NACA before exposure to H 2 O 2 and the group treated with NACA after exposure to H 2 O 2 , exhibited significantly higher cell viability compared to the H 2 O 2 group (p < 0.001 and p < 0.01, respectively). Discussion: The increased viability of the cells may indicate that NACA could play an important role in reducing oxidative stress. Taking the results from our previous study into consideration, our findings may strengthen the theory that NACA may have organ protective properties for neonates exposed to oxidative stress.
- Devasagayam, T.P., Tilak, J.C., Boloor, K.K., Sane, K.S., Ghaskadbi, S.S. and Lele, R.D. (2004) Free Radicals and Antioxidants in Human Health: Current Status and Future Prospects. The Journal of the Association of Physicians of India, 52, 794-804.
- Benterud, T., Ystgaard, M.B., Manueldas, S., Pankratov, L., Alfaro-Cervello, C., Florholmen, G., Ahmed, M.S., Sandvik, L., Norgren, S., Bjoras, M., et al. (2016) N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia. Neonatology, 111, 12-21. https://doi.org/10.1159/000447255
- Osterholt, H.C., Dannevig, I., Wyckoff, M.H., Liao, J., Akgul, Y., Ramgopal, M., Mija, D.S., Cheong, N., Longoria, C., Mahendroo, M., et al. (2012) Antioxidant Protects against Increases in Low Molecular Weight Hyaluronan and Inflammation in Asphyxiated Newborn Pigs Resuscitated with 100% Oxygen. PloS ONE, 7, e38839. https://doi.org/10.1371/journal.pone.0038839
- Gupta, B.D., Sharma, P., Bagla, J., Parakh, M. and Soni, J.P. (2005) Renal Failure in Asphyxiated Neonates. Indian Pediatrics, 42, 928-934.
- Alaro, D., Bashir, A., Musoke, R. and Wanaiana, L. (2014) Prevalence and Outcomes of Acute Kidney Injury in Term Neonates with Perinatal Asphyxia. African Health Sciences, 14, 682-688. https://doi.org/10.4314/ahs.v14i3.26
- Gong, X., Celsi, G., Carlsson, K. and Norgren, S. (2012) Protective Effects of N-Acetylcysteine Amide (NACA) on Gentamicin-Induced Apoptosis in LLC-PK1 Cells. Renal Failure, 34, 487-494. https://doi.org/10.3109/0886022X.2012.655684
- Gong, X., Celsi, G., Carlsson, K., Norgren, S. and Chen, M. (2010) N-Acetylcysteine Amide Protects Renal Proximal Tubular Epithelial Cells against Iohexol-Induced Apoptosis by Blocking p38 MAPK and iNOS Signaling. American Journal of Nephrology, 31, 178-188. https://doi.org/10.1159/000268161
- Mosmann, T. (1983) Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays. Journal of Immunological Methods, 65, 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
- Penugonda, S., Mare, S., Goldstein, G., Banks, W.A. and Ercal, N. (2005) Effects of N-Acetylcysteine Amide (NACA), a Novel Thiol Antioxidant against Glutamate-Induced Cytotoxicity in Neuronal Cell Line PC12. Brain Research, 1056, 132-138. https://doi.org/10.1016/j.brainres.2005.07.032
- Sunitha, K., Hemshekhar, M., Thushara, R.M., Santhosh, M.S., Yariswamy, M., Kemparaju, K. and Girish, K.S. (2013) N-Acetylcysteine Amide: A Derivative to Fulfill the Promises of N-Acetylcysteine. Free Radical Research, 47, 357-367. https://doi.org/10.3109/10715762.2013.781595