The Assessment of Meloxicam Phototoxicity in Human Normal Skin Cells: In Vitro Studies on Dermal Fibroblasts and Epidermal Melanocytes

Karkoszka, Marta; Rok, Jakub; Banach, Klaudia; Kowalska, Justyna; Rzepka, Zuzanna; Wrześniok, Dorota

doi:10.3390/molecules27134215

Cited by 3 publications

(7 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the phototoxic action of HCT and FUR led to genetic material damage and DNA fragmentation as evidenced by an increase in the percentage of cells in the subG1 phase. Similar changes in the cell cycle were caused by phototoxic action of meloxicam in melanocytes and fibroblasts-the drug caused a decrease in the percentage of cells in the G1/G0 phase [45]. The analysis of the effect of lomefloxacin and UVAR on the fibroblast cell cycle showed similar results relating to the percentage of cells in the G1/G0 and G2/M phases as the HCT and FUR studies.…”

Section: Discussionmentioning

confidence: 53%

“…The obtained results allow us to conclude that HCT is the drug causing greater oxidationreduction disorders than furosemide, while fibroblasts are more sensitive cells to oxygen homeostasis disorder than melanocytes. Many drugs with high phototoxic potential, i.e., lomefloxacin or meloxicam, induced disturbances of redox homeostasis in skin cells which resulted in an increase in ROS levels, a decrease in the percentage of cells with high levels of reduced thiols, similar to the tested HCT and FUR [45,48].…”

Section: Discussionmentioning

confidence: 80%

“…A similar experimental model was previously used to investigate the phototoxicity of fluoroquinolones and meloxicam against human normal skin cells. It has been shown that the tested drugs used in combination with UVA inhibit the proliferation of fibroblasts and melanocytes, and the obtained effect depends on the concentration of the analysed substances [45,46]. The presented results showing phototoxic properties of HCT and FUR was obtained during various analysis, including the number and viability of cells as well as microscopic images.…”

Section: Discussionmentioning

confidence: 83%

“…The mitochondrial potential analysis was performed using the NucleoCounter ®® NC-3000™ imaging cytometer according to the procedure described earlier [45,56]. The ability of JC-1 to accumulate in the mitochondrial matrix of cells with high transmembrane mitochondrial potential and the emission of red fluorescence allowed to determine the percentage of normal cells.…”

Section: Mitochondrial Potential Analysismentioning

confidence: 99%

“…Intracellular reduced thiol levels in melanocytes and fibroblasts were measured using the image cytometer NucleoCounter ®® NC-3000™ following the protocol described previously [45,56]. The analysis is based on the use of VitaBright-48™ dye, which reacts with reduced thiols to create a fluorescent product.…”

Section: The Assessment Of the Intracellular Content Of Reduced Thiolsmentioning

confidence: 99%

See 4 more Smart Citations

Phototoxic Reactions Inducted by Hydrochlorothiazide and Furosemide in Normal Skin Cells—In Vitro Studies on Melanocytes and Fibroblasts

Karkoszka,

Rok,

Rzepka

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

Hypertension is known to be a multifactorial disease associated with abnormalities in neuroendocrine, metabolic, and hemodynamic systems. Poorly controlled hypertension causes more than one in eight premature deaths worldwide. Hydrochlorothiazide (HCT) and furosemide (FUR), being first-line drugs in the treatment of hypertension, are among others the most frequently prescribed drugs in the world. Currently, many pharmacoepidemiological data associate the use of these diuretics with an increased risk of adverse phototoxic reactions that may induce the development of melanoma and non-melanoma skin cancers. In this study, the cytotoxic and phototoxic potential of HCT and FUR against skin cells varied by melanin pigment content was assessed for the first time. The results showed that both drugs reduced the number of metabolically active normal skin cells in a dose-dependent manner. UVA irradiation significantly increased the cytotoxicity of HCT towards fibroblasts by approximately 40% and melanocytes by almost 20% compared to unirradiated cells. In the case of skin cells exposed to FUR and UVA radiation, an increase in cytotoxicity by approximately 30% for fibroblasts and 10% for melanocytes was observed. Simultaneous exposure of melanocytes and fibroblasts to HCT or FUR and UVAR caused a decrease in cell viability, and number, which was confirmed by microscopic assessment of morphology. The phototoxic effect of HCT and FUR was associated with the disturbance of redox homeostasis confirming the oxidative stress as a mechanism of phototoxic reaction. UVA-irradiated drugs increased the generation of ROS by 10–150%, and oxidized intracellular thiols. A reduction in mitochondrial potential of almost 80% in melanocytes exposed to HCT and UVAR and 60% in fibroblasts was found due to oxidative stress occurrence. In addition, HCT and FUR have been shown to disrupt the cell cycle of normal skin cells. Finally, it can be concluded that HCT is the drug with a stronger phototoxic effect, and fibroblasts turn out to be more sensitive cells to the phototoxic effect of tested drugs.

show abstract

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 83%

Section: Mitochondrial Potential Analysismentioning

confidence: 99%

Section: The Assessment Of the Intracellular Content Of Reduced Thiolsmentioning

confidence: 99%

See 3 more Smart Citations

Phototoxic Reactions Inducted by Hydrochlorothiazide and Furosemide in Normal Skin Cells—In Vitro Studies on Melanocytes and Fibroblasts

Karkoszka,

Rok,

Rzepka

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

Phototoxic action of meloxicam contributes to dysregulation of redox homeostasis in normal human skin cells – Molecular and biochemical analysis of antioxidant enzymes in melanocytes and fibroblasts

Karkoszka,

Rok,

Kowalska

et al. 2024

Toxicology in Vitro

View full text Add to dashboard Cite

Exploring COX-Independent Pathways: A Novel Approach for Meloxicam and Other NSAIDs in Cancer and Cardiovascular Disease Treatment

Cheng,

Hu,

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

As a fundamental process of innate immunity, inflammation is associated with the pathologic process of various diseases and constitutes a prevalent risk factor for both cancer and cardiovascular disease (CVD). Studies have indicated that several non-steroidal anti-inflammatory drugs (NSAIDs), including Meloxicam, may prevent tumorigenesis, reduce the risk of carcinogenesis, improve the efficacy of anticancer therapies, and reduce the risk of CVD, in addition to controlling the body’s inflammatory imbalances. Traditionally, most NSAIDs work by inhibiting cyclooxygenase (COX) activity, thereby blocking the synthesis of prostaglandins (PGs), which play a role in inflammation, cancer, and various cardiovascular conditions. However, long-term COX inhibition and reduced PGs synthesis can result in serious side effects. Recent studies have increasingly shown that some selective COX-2 inhibitors and NSAIDs, such as Meloxicam, may exert effects beyond COX inhibition. This emerging understanding prompts a re-evaluation of the mechanisms by which NSAIDs operate, suggesting that their benefits in cancer and CVD treatment may not solely depend on COX targeting. In this review, we will explore the potential COX-independent mechanisms of Meloxicam and other NSAIDs in addressing oncology and cardiovascular health.

show abstract

The Assessment of Meloxicam Phototoxicity in Human Normal Skin Cells: In Vitro Studies on Dermal Fibroblasts and Epidermal Melanocytes

Cited by 3 publications

References 50 publications

Phototoxic Reactions Inducted by Hydrochlorothiazide and Furosemide in Normal Skin Cells—In Vitro Studies on Melanocytes and Fibroblasts

Phototoxic Reactions Inducted by Hydrochlorothiazide and Furosemide in Normal Skin Cells—In Vitro Studies on Melanocytes and Fibroblasts

Phototoxic action of meloxicam contributes to dysregulation of redox homeostasis in normal human skin cells – Molecular and biochemical analysis of antioxidant enzymes in melanocytes and fibroblasts

Exploring COX-Independent Pathways: A Novel Approach for Meloxicam and Other NSAIDs in Cancer and Cardiovascular Disease Treatment

Contact Info

Product

Resources

About