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Volume 25
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10.3390/ijms25021286
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Article

Buffering Mitigates Chondrocyte Oxidative Stress, Metabolic Dysfunction, and Death Induced by Normal Saline: Formulation of a Novel Arthroscopic Irrigant

by
Arman Hlas
1,
Venkateswaran Ganesh
2,3,
Jaison Marks
2,3,
Rui He
4,
Aliasger K. Salem
4,
Joseph A. Buckwalter
2,
Kyle R. Duchman
2,
Kyungsup Shin
5,
James A. Martin
2,3,* and
Dongrim Seol
2,5,*
1
Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
2
Department of Orthopedics and Rehabilitation, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
3
Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242, USA
4
Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA
5
Department of Orthodontics, College of Dentistry and Dental Clinics, University of Iowa, Iowa City, IA 52242, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(2), 1286; https://doi.org/10.3390/ijms25021286
Submission received: 21 December 2023 / Revised: 12 January 2024 / Accepted: 17 January 2024 / Published: 20 January 2024
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Oxidative Stress-Related Diseases 3.0)
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Abstract

For decades, surgeons have utilized 0.9% normal saline (NS) for joint irrigation to improve visualization during arthroscopic procedures. This continues despite mounting evidence that NS exposure impairs chondrocyte metabolism and compromises articular cartilage function. We hypothesized that chondrocyte oxidative stress induced by low pH is the dominant factor driving NS toxicity, and that buffering NS to increase its pH would mitigate these effects. Effects on chondrocyte viability, reactive oxygen species (ROS) production, and overall metabolic function were assessed. Even brief exposure to NS caused cell death, ROS overproduction, and disruption of glycolysis, pentose phosphate, and tricarboxylic acid (TCA) cycle pathways. NS also stimulated ROS overproduction in synovial cells that could adversely alter the synovial function and subsequently the entire joint health. Buffering NS with 25 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) significantly increased chondrocyte viability, reduced ROS production, and returned metabolite levels to near control levels while also reducing ROS production in synovial cells. These results confirm that chondrocytes and synoviocytes are vulnerable to insult from the acidic pH of NS and demonstrate that adding a buffering agent to NS averts many of its most harmful effects.
Keywords: arthroscopic irrigation; normal saline; acidity; oxidative stress; metabolic dysfunction; cell death; HEPES; reactive oxygen species; chondrocyte; synoviocyte arthroscopic irrigation; normal saline; acidity; oxidative stress; metabolic dysfunction; cell death; HEPES; reactive oxygen species; chondrocyte; synoviocyte

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MDPI and ACS Style

Hlas, A.; Ganesh, V.; Marks, J.; He, R.; Salem, A.K.; Buckwalter, J.A.; Duchman, K.R.; Shin, K.; Martin, J.A.; Seol, D. Buffering Mitigates Chondrocyte Oxidative Stress, Metabolic Dysfunction, and Death Induced by Normal Saline: Formulation of a Novel Arthroscopic Irrigant. Int. J. Mol. Sci. 2024, 25, 1286. https://doi.org/10.3390/ijms25021286

AMA Style

Hlas A, Ganesh V, Marks J, He R, Salem AK, Buckwalter JA, Duchman KR, Shin K, Martin JA, Seol D. Buffering Mitigates Chondrocyte Oxidative Stress, Metabolic Dysfunction, and Death Induced by Normal Saline: Formulation of a Novel Arthroscopic Irrigant. International Journal of Molecular Sciences. 2024; 25(2):1286. https://doi.org/10.3390/ijms25021286

Chicago/Turabian Style

Hlas, Arman, Venkateswaran Ganesh, Jaison Marks, Rui He, Aliasger K. Salem, Joseph A. Buckwalter, Kyle R. Duchman, Kyungsup Shin, James A. Martin, and Dongrim Seol. 2024. "Buffering Mitigates Chondrocyte Oxidative Stress, Metabolic Dysfunction, and Death Induced by Normal Saline: Formulation of a Novel Arthroscopic Irrigant" International Journal of Molecular Sciences 25, no. 2: 1286. https://doi.org/10.3390/ijms25021286

APA Style

Hlas, A., Ganesh, V., Marks, J., He, R., Salem, A. K., Buckwalter, J. A., Duchman, K. R., Shin, K., Martin, J. A., & Seol, D. (2024). Buffering Mitigates Chondrocyte Oxidative Stress, Metabolic Dysfunction, and Death Induced by Normal Saline: Formulation of a Novel Arthroscopic Irrigant. International Journal of Molecular Sciences, 25(2), 1286. https://doi.org/10.3390/ijms25021286

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