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Home / Equine Research Bank / Curr Res Pharmacol Drug Discov / Bupivacaine in combination with sildenafil (Viagra) and vita...
Current research in pharmacology and drug discovery2021; 2; 100066; doi: 10.1016/j.crphar.2021.100066

Bupivacaine in combination with sildenafil (Viagra) and vitamin D3 have anti-inflammatory effects in osteoarthritic chondrocytes.

Abstract: To treat osteoarthritic chondrocytes and thereby reduce the inflammation with a drug combination that primarily affects 5-HT- and ATP-evoked Ca2+ signaling. In osteoarthritic chondrocytes, Ca2+ signaling is elevated, resulting in increased production of ATP and inflammatory mediators. The expression of TLR4 and Na+/K+-ATPase was used to evaluate the inflammatory status of the cells. Methods: Equine chondrocytes were collected from joints with mild structural osteoarthritic changes and cultured in monolayers. The cells were treated with a combination of bupivacaine (1 pM) and sildenafil (1 ​μM) in combination with vitamin D3 (100 ​nM). A high-throughput screening system, the Flexstation 3 microplate reader, was used to measure intra- and extracellular Ca2+ signaling after exposure to 5-HT, glutamate, or ATP. Expression of inflammatory receptors was assessed by Western blotting. Results: Drug treatment substantially reduced 5-HT- and ATP-evoked intracellular Ca2+ release and TLR4 expression compared to those in untreated chondrocytes. The combination of sildenafil, vitamin D3 together with metformin, as the ability to take up glucose is limited, increased Na+/K+-ATPase expression. Conclusions: The combination of these three therapeutic substances at concentrations much lower than usually used, reduced expression of the inflammatory receptor TLR4 and increased the cell membrane enzyme Na+/K+-ATPase, which regulates cell volume and reduces increased intracellular Ca2+ concentrations. These remarkable results indicate that this drug combination has disease-modifying osteoarthritis drug (DMOAD) properties and may be a new clinical therapy for osteoarthritis (OA).
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Publication Date: 2021-10-19 PubMed ID: 34909684PubMed Central: PMC8663929DOI: 10.1016/j.crphar.2021.100066Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the anti-inflammatory effects of Bupivacaine, sildenafil (Viagra), and Vitamin D3 when used in combination as a therapeutic treatment for osteoarthritis, indicating promising results of reduced inflammation and improved cell function.

Research Focus and Background

  • The study aims at treating osteoarthritic chondrocytes (cartilage cells) to reduce inflammation using a unique combination of drugs, as these cells exhibit increased Ca signaling resulting in overproduction of ATP and inflammatory mediators.
  • The inflammation status of these cells is gauged through the expression of Toll-Like Receptor 4 (TLR4) and Sodium-potassium pump (Na/K-ATPase).

Methods Used

  • Horse chondrocytes collected from mild osteoarthritic-affected joints were cultured. Treatment included bupivacaine (a local anaesthetic also used to treat nerve pain), sildenafil (a drug that treats erectile dysfunction and pulmonary arterial hypertension), and vitamin D3.
  • The researchers used a high-throughput screening system, namely a Flexstation 3 microplate reader, to measure intra and extracellular Ca signaling upon exposure to 5-HT (a hormone used by neurons), glutamate (a prime neurotransmitter), or ATP (an energy-carrying molecule).
  • Inflammatory receptor expression was analyzed using Western blotting, an extensively used tool in cell and molecular biology research to detect proteins.

Key Findings

  • Administering the drug combination significantly reduced the impact of 5-HT and ATP in promoting the release of intracellular Ca as well as the expression of TLR4, an inflammation marker, compared to untreated chondrocytes.
  • This drug combination along with metformin, an antidiabetic drug, resulted in an increase in Na/K-ATPase expression. This is significant, as osteoarthritic chondrocytes have limited glucose intake capacity and Na/K-ATPase has a key role in controlling cell volume and reducing intracellular Ca concentrations.

Conclusions

  • The research concluded that significantly lower concentrations of these three substances, together, minimized the expression of TLR4, an inflammatory receptor, and enhanced the presence of Na/K-ATPase in the cell membrane, leading to a regulation of cell volume and decrease in intracellular Ca concentrations.
  • The significant effectiveness of this combination suggests that it may possess properties similar to disease-modifying osteoarthritis drugs (DMOAD), and could potentially be considered a new therapeutic approach for treating osteoarthritis patients.

Cite This Article

APA
Hansson E, Skiöldebrand E. (2021). Bupivacaine in combination with sildenafil (Viagra) and vitamin D3 have anti-inflammatory effects in osteoarthritic chondrocytes. Curr Res Pharmacol Drug Discov, 2, 100066. https://doi.org/10.1016/j.crphar.2021.100066

Publication

Current research in pharmacology and drug discovery
ISSN: 2590-2571
NlmUniqueID: 9918300982506676
Country: Netherlands
Language: English
Volume: 2
Pages: 100066

Researcher Affiliations

Hansson, Elisabeth
  • Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Skiöldebrand, Eva
  • Department of Pathology, Institute of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
  • Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.

Conflict of Interest Statement

The authors declare no potential conflicts of interest with respect to the research, authorship, or publication of this article.

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