S-ALLYL-L-CYSTEINE-INDUCED ANTI-INFLAMMATORY AND ANTI-APOPTOTIC EFFECTS IN CHONDROCYTES IS ASSOCIATED WITH SUPPRESSION OF THE MITOCHONDRIAL INFLAMMATION PATHWAY

Authors

  • H AHMED National Centre of Excellence in Molecular Biology, University of The Punjab, Lahore, Pakistan
  • N FAZAL National Centre of Excellence in Molecular Biology, University of The Punjab, Lahore, Pakistan
  • MR AHMAD Department of Molecular Biology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan
  • B IJAZ National Centre of Excellence in Molecular Biology, University of The Punjab, Lahore, Pakistan
  • AZ BILAL Rahbar Medical and Dental College Lahore, Pakistan
  • S ILYAS Ghurki Trust and Teaching Hospital, Lahore, Pakistan
  • K MALIK National Centre of Excellence in Molecular Biology, University of The Punjab, Lahore, Pakistan
  • N LATIEF National Centre of Excellence in Molecular Biology, University of The Punjab, Lahore, Pakistan

DOI:

https://doi.org/10.54112/bcsrj.v2022i1.179

Keywords:

Osteoarthritis, Chondrocytes, S-Allyl-L-Cysteine (SAC), Antioxidant, Mitochondrial Inflammation, Anti-apoptotic, Anti-inflammation

Abstract

One  major aspects to consider while dealing with osteoarthritis is oxidative stress. This deleterious oxidative stress is responsible for the increased production of Reactive Oxygen Species and triggers several inflammatory pathways, including Mitochondrial Inflammation Pathway (MIP), which leads the cell to apoptosis. Chondrocytes, under oxidative stress, are unable to synthesize cartilage efficiently. S-Allyl-L-Cysteine (SAC) is known to be a potent natural, water-soluble antioxidant derived from garlic whose antioxidant properties have been evaluated in several diseases at the molecular level; other than osteoarthritis. Herein, we investigated the potential of S-Allyl-L-Cysteine (SAC) preconditioning of chondrocytes against oxidative stress-mediated mitochondrial inflammation. SAC priming alleviated oxidative stress-induced injuries by significantly improved cell viability, morphology and activated cell migration. In addition, decreased lactate dehydrogenease,  increased superoxide dismutase release and retention of glycosaminoglycans were observed.SAC preconditioning ameliorated the injurious effects of oxidative stress as revealed by significant downregulation in gene expression of hypoxia-induciblefactor 1α (Hif-1α), Xanthine Oxidase (XO), Caspase-9 (Casp-9), Caspase-3(Casp-3), Interleukin 1 beta (IL-1β) and inducible nitric oxide synthase (iNOS). These findings suggest that SAC preconditioning might enhance the antioxidant and anti-inflammatory efficacy of chondrocytes  by regulating the MIP pathway and improving cellular responses.

Downloads

Download data is not yet available.

References

Ali, F., Khan, M., Khan, S. N., and Riazuddin, S. (2016). N-Acetyl cysteine protects diabetic mouse derived mesenchymal stem cells from hydrogen-peroxide-induced injury: A novel hypothesis for autologous stem cell transplantation. Journal of the Chinese Medical Association 79, 122-129.

Alvarez-Suarez, J. M., Giampieri, F., Gasparrini, M., Mazzoni, L., Forbes-Hernández, T. Y., Afrin, S., and Battino, M. (2018). Guava (Psidium guajava L. cv. Red Suprema) Crude Extract Protect Human Dermal Fibroblasts against Cytotoxic Damage Mediated by Oxidative Stress. Plant Foods for Human Nutrition 73, 18-24.

Bahule, B., Mahajan, R., Patil, B., and Khune, D. (2018). Phytochemical assay and study of antioxidant activity of plant extracts obtained from tridax procumbens employing radical scavenging method. International Journal of Scientific Research 6.

Boyd, J. M., Malstrom, S., Subramanian, T., Venkatesh, L., Schaeper, U., Elangovan, B., D'Sa-Eipper, C., and Chinnadurai, G. (1994). Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins. Cell 79, 341-351.

Brown, G. C. (1999). Nitric oxide and mitochondrial respiration. Biochimica et Biophysica Acta (BBA)-Bioenergetics 1411, 351-369.

Brown, G. C. (2001). Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase. Biochimica et Biophysica Acta (BBA)-Bioenergetics 1504, 46-57.

Colín-González, A. L., Ali, S. F., Túnez, I., and Santamaría, A. (2015). On the antioxidant, neuroprotective and anti-inflammatory properties of S-allyl cysteine: an update. Neurochemistry international 89, 83-91.

Colín-González, A. L., Santana, R. A., Silva-Islas, C. A., Chánez-Cárdenas, M. E., Santamaría, A., and Maldonado, P. D. (2012). The antioxidant mechanisms underlying the aged garlic extract-and S-allylcysteine-induced protection. Oxidative medicine and cellular longevity 2012.

Escames, G., López, L. C., Ortiz, F., López, A., García, J. A., Ros, E., and Acuña‐Castroviejo, D. (2007). Attenuation of cardiac mitochondrial dysfunction by melatonin in septic mice. The FEBS Journal 274, 2135-2147.

Esteban, F. J., Pedrosa, J. A., Jiménez, A., Fernández, A. P., Bentura, M. a. L., Martı́nez-Murillo, R., Rodrigo, J., and Peinado, M. a. A. (1997). Distribution of neuronal nitric oxide synthase in the rat liver. Neuroscience letters 226, 99-102.

Fosang, A. J., and Beier, F. (2011). Emerging frontiers in cartilage and chondrocyte biology. Best practice & research Clinical rheumatology 25, 751-766.

Fulda, S., Meyer, E., and Debatin, K.-M. (2000). Metabolic inhibitors sensitize for CD95 (APO-1/Fas)-induced apoptosis by down-regulating Fas-associated death domain-like interleukin 1-converting enzyme inhibitory protein expression. Cancer research 60, 3947-3956.

Gitto, E., Karbownik, M., Reiter, R. J., Tan, D. X., Cuzzocrea, S., Chiurazzi, P., Cordaro, S., Corona, G., Trimarchi, G., and Barberi, I. (2001). Effects of melatonin treatment in septic newborns. Pediatric research 50, 756-760.

Gouze, J., Bianchi, A., Becuwe, P., Dauca, M., Netter, P., Magdalou, J., Terlain, B., and Bordji, K. (2002). Glucosamine modulates IL‐1‐induced activation of rat chondrocytes at a receptor level, and by inhibiting the NF‐κB pathway. FEBS letters 510, 166-170.

Greijer, A., and Van der Wall, E. (2004). The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis. Journal of clinical pathology 57, 1009-1014.

Guo, L., Liu, J., and Xia, Z. (2009). Geniposide inhibits CoCl2-induced PC12 cells death via the mitochondrial pathway. Chinese medical journal 122, 2886-2892.

Hejazi, I. I., Khanam, R., Mehdi, S. H., Bhat, A. R., Rizvi, M. M. A., Islam, A., Thakur, S. C., and Athar, F. (2017). New insights into the antioxidant and apoptotic potential of Glycyrrhiza glabra L. during hydrogen peroxide mediated oxidative stress: an in vitro and in silico evaluation. Biomedicine & Pharmacotherapy 94, 265-279.

Javed, H., Khan, M. M., Khan, A., Vaibhav, K., Ahmad, A., Khuwaja, G., Ahmed, M. E., Raza, S. S., Ashafaq, M., and Tabassum, R. (2011). S-allyl cysteine attenuates oxidative stress associated cognitive impairment and neurodegeneration in mouse model of streptozotocin-induced experimental dementia of Alzheimer's type. Brain research 1389, 133-142.

Jung, J.-Y., and Kim, W.-J. (2004). Involvement of mitochondrial-and Fas-mediated dual mechanism in CoCl 2-induced apoptosis of rat PC12 cells. Neuroscience letters 371, 85-90.

Khan, I., Gilbert, S., Caterson, B., Sandell, L., and Archer, C. (2008). Oxidative stress induces expression of osteoarthritis markers procollagen IIA and 3B3 (−) in adult bovine articular cartilage. Osteoarthritis and cartilage 16, 698-707.

King, K., and Rosenthal, A. (2015). The adverse effects of diabetes on osteoarthritis: update on clinical evidence and molecular mechanisms. Osteoarthritis and cartilage 23, 841-850.

Lan, A.-P., Xiao, L.-C., Yang, Z.-L., Yang, C.-T., Wang, X.-Y., Chen, P.-X., Gu, M.-F., and Feng, J.-Q. (2012). Interaction between ROS and p38MAPK contributes to chemical hypoxia-induced injuries in PC12 cells. Molecular medicine reports 5, 250-255.

Lan, A., Liao, X., Mo, L., Yang, C., Yang, Z., Wang, X., Hu, F., Chen, P., Feng, J., and Zheng, D. (2011). Hydrogen sulfide protects against chemical hypoxia-induced injury by inhibiting ROS-activated ERK1/2 and p38MAPK signaling pathways in PC12 cells. PLoS One 6, e25921.

Lawson, L. D. (1998). Garlic: a review of its medicinal effects and indicated active compounds. ACS Publications.

Lee, D. Y., Li, H., Lim, H. J., Lee, H. J., Jeon, R., and Ryu, J.-H. (2012). Anti-inflammatory activity of sulfur-containing compounds from garlic. Journal of medicinal food 15, 992-999.

Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., and Wang, X. (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-489.

Li, W., Jiang, B., Cao, X., Xie, Y., and Huang, T. (2017). Protective effect of lycopene on fluoride-induced ameloblasts apoptosis and dental fluorosis through oxidative stress-mediated Caspase pathways. Chemico-biological interactions 261, 27-34.

Lind, M., Hayes, A., Caprnda, M., Petrovic, D., Rodrigo, L., Kruzliak, P., and Zulli, A. (2017). Inducible nitric oxide synthase: good or bad? Biomedicine & Pharmacotherapy 93, 370-375.

Maldonado, P. D., Barrera, D., Rivero, I., Mata, R., Medina-Campos, O. N., Hernández-Pando, R., and Pedraza-Chaverrí, J. (2003). Antioxidant S-allylcysteine prevents gentamicin-induced oxidative stress and renal damage. Free Radical Biology and Medicine 35, 317-324.

Mathy-Hartert, M., Hogge, L., Sanchez, C., Deby-Dupont, G., Crielaard, J.-M., and Henrotin, Y. (2008). Interleukin-1β and interleukin-6 disturb the antioxidant enzyme system in bovine chondrocytes: a possible explanation for oxidative stress generation. Osteoarthritis and Cartilage 16, 756-763.

Medina-Campos, O. N., Barrera, D., Segoviano-Murillo, S., Rocha, D., Maldonado, P. D., Mendoza-Patiño, N., and Pedraza-Chaverri, J. (2007). S-allylcysteine scavenges singlet oxygen and hypochlorous acid and protects LLC-PK1 cells of potassium dichromate-induced toxicity. Food and Chemical Toxicology 45, 2030-2039.

Musumeci, G., Loreto, C., Carnazza, M. L., and Martinez, G. (2011). Characterization of apoptosis in articular cartilage derived from the knee joints of patients with osteoarthritis. Knee Surgery, Sports Traumatology, Arthroscopy 19, 307-313.

Nagata, S., and Golstein, P. (1995). The Fas death factor. Science 267, 1449-1456.

Najeeb, Q., and Aziz, R. (2015). Comparison of Alkaline phosphatase, Lactate Dehydrogenase and Acid Phosphatase Levels in Serum and Synovial Fluid between Patients with Rheumatoid Arthritis and Osteoarthritis. Int. J. Sci. Res. 4, 4.

Nicholson, D. W., and Thornberry, N. A. (1997). Caspases: killer proteases. Trends in biochemical sciences 22, 299-306.

Orozco-Ibarra, M., Muñoz-Sánchez, J., Zavala-Medina, M. E., Pineda, B., Magaña-Maldonado, R., Vázquez-Contreras, E., Maldonado, P. D., Pedraza-Chaverri, J., and Chánez-Cárdenas, M. E. (2016). Aged garlic extract and S-allylcysteine prevent apoptotic cell death in a chemical hypoxia model. Biological research 49, 7.

Osman, W., Nurfarahin, W., Lau, S. F., and Mohamed, S. (2017). Scopoletin‐standardized Morinda elliptica leaf extract suppressed inflammation and cartilage degradation to alleviate osteoarthritis: A preclinical study. Phytotherapy Research 31, 1954-1961.

Pfander, D., and Gelse, K. (2007). Hypoxia and osteoarthritis: how chondrocytes survive hypoxic environments. Current opinion in rheumatology 19, 457-462.

Prime, T. A., Blaikie, F. H., Evans, C., Nadtochiy, S. M., James, A. M., Dahm, C. C., Vitturi, D. A., Patel, R. P., Hiley, C. R., and Abakumova, I. (2009). A mitochondria-targeted S-nitrosothiol modulates respiration, nitrosates thiols, and protects against ischemia-reperfusion injury. Proceedings of the National Academy of Sciences 106, 10764-10769.

Ramalingam, L., Menikdiwela, K., LeMieux, M., Dufour, J. M., Kaur, G., Kalupahana, N., and Moustaid-Moussa, N. (2017). The renin angiotensin system, oxidative stress and mitochondrial function in obesity and insulin resistance. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1863, 1106-1114.

Roughley, P. J., and Mort, J. S. (2014). The role of aggrecan in normal and osteoarthritic cartilage. Journal of experimental orthopaedics 1, 8.

Rousset, F., Hazane-Puch, F., Pinosa, C., Nguyen, M. V. C., Grange, L., Soldini, A., Rubens-Duval, B., Dupuy, C., Morel, F., and Lardy, B. (2015). IL-1beta mediates MMP secretion and IL-1beta neosynthesis via upregulation of p22phox and NOX4 activity in human articular chondrocytes. Osteoarthritis and cartilage 23, 1972-1980.

Schild, L., Reinheckel, T., Reiser, M., Horn, T. F., Wolf, G., and Augustin, W. (2003). Nitric oxide produced in rat liver mitochondria causes oxidative stress and impairment of respiration after transient hypoxia. The FASEB journal 17, 2194-2201.

Sun, W., Depping, R., and Jelkmann, W. (2014). Interleukin-1β promotes hypoxia-induced apoptosis of glioblastoma cells by inhibiting hypoxia-inducible factor-1 mediated adrenomedullin production. Cell death & disease 5, e1020.

Takemura, S., Minamiyama, Y., Inoue, M., Kubo, S., Hirohashi, K., and Kinoshita, H. (2000). Nitric oxide synthase inhibitor increases hepatic injury with formation of oxidative DNA damage and microcirculatory disturbance in endotoxemic rats. Hepato-gastroenterology 47, 1364-1370.

Tsai, S.-J., Chiu, C. P., Yang, H.-T., and Yin, M.-C. (2011). s-Allyl cysteine, s-ethyl cysteine, and s-propyl cysteine alleviate β-amyloid, glycative, and oxidative injury in brain of mice treated by D-galactose. Journal of agricultural and food chemistry 59, 6319-6326.

Wang, G., Hazra, T. K., Mitra, S., Lee, H.-M., and Englander, E. W. (2000). Mitochondrial DNA damage and a hypoxic response are induced by CoCl2 in rat neuronal PC12 cells. Nucleic acids research 28, 2135-2140.

Wei, M. C., Zong, W.-X., Cheng, E. H.-Y., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B., and Korsmeyer, S. J. (2001). Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292, 727-730.

Weydert, C. J., and Cullen, J. J. (2010). Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nature protocols 5, 51.

Würstle, M. L., Laussmann, M. A., and Rehm, M. (2012). The central role of initiator caspase-9 in apoptosis signal transduction and the regulation of its activation and activity on the apoptosome. Experimental cell research 318, 1213-1220.

Yudoh, K., Nakamura, H., Masuko-Hongo, K., Kato, T., and Nishioka, K. (2005). Catabolic stress induces expression of hypoxia-inducible factor (HIF)-1α in articular chondrocytes: involvement of HIF-1α in the pathogenesis of osteoarthritis. Arthritis research & therapy 7, R904.

Zhao, Z.-y., Gao, Y.-y., Gao, L., Zhang, M., Wang, H., and Zhang, C.-h. (2017). Protective effects of bellidifolin in hypoxia-induced in pheochromocytoma cells (PC12) and underlying mechanisms. Journal of Toxicology and Environmental Health, Part A 80, 1187-1192.

Zou, W., Zeng, J., Zhuo, M., Xu, W., Sun, L., Wang, J., and Liu, X. (2002). Involvement of caspase‐3 and p38 mitogen‐activated protein kinase in cobalt chloride‐induced apoptosis in PC12 cells. Journal of neuroscience research 67, 837-843.

Downloads

Published

2022-12-30

How to Cite

AHMED, H., FAZAL, N., AHMAD, M., IJAZ, B., BILAL, A., ILYAS, S., MALIK, K., & LATIEF, N. (2022). S-ALLYL-L-CYSTEINE-INDUCED ANTI-INFLAMMATORY AND ANTI-APOPTOTIC EFFECTS IN CHONDROCYTES IS ASSOCIATED WITH SUPPRESSION OF THE MITOCHONDRIAL INFLAMMATION PATHWAY. Biological and Clinical Sciences Research Journal, 2022(1). https://doi.org/10.54112/bcsrj.v2022i1.179

Issue

Section

Original Research Articles