scholarly journals Effect of selected nonsteroidal anti-inflammatory drugs on the viability of canine osteosarcoma cells of the D-17 line: in vitro studies

2019 ◽  
Vol 63 (3) ◽  
pp. 399-403 ◽  
Author(s):  
Dominik Poradowski ◽  
Bożena Obmińska-Mrukowicz

Abstract Introduction Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in veterinary medicine. They are used in pain control and in anti-inflammatory and antipyretic therapies. Some NSAIDs, e.g piroxicam, also have a documented anticancer effect. The objective of this study was to evaluate which of the commonly used NSAIDs (etodolac, flunixin, tolfenamic acid, carprofen, and ketoprofen) are cytotoxic to the D-17 cell line of canine osteosarcoma. Material and Methods The viability of the cells was evaluated using the MTT assay. Four independent repetitions were performed and the results are given as the average of these values; EC50 values (half maximal effective concentration) were also calculated. Results The analysis of results showed that carprofen and tolfenamic acid displayed the highest cytotoxicity. Other drugs either did not provide such effects or they were very poor. For carprofen, it was possible to determine an EC50 which fell within the limits of concentrations obtainable in canine serum after the administration of routinely used doses. Conclusion The results are promising but further studies should be conducted to confirm them, since this study is only preliminary. The possibility of introducing carprofen and tolfenamic acid into the routine treatment of osteosarcoma in dogs should be considered.

Author(s):  
Juan Ramón Zapata-Morales ◽  
Angel Josabad Alonso-Castro ◽  
Gloria Sarahí Muñoz-Martínez ◽  
María Mayela Martínez-Rodríguez ◽  
Mónica Esther Nambo-Arcos ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3303
Author(s):  
Amina M. G. Zedan ◽  
Mohamed I. Sakran ◽  
Omar Bahattab ◽  
Yousef M. Hawsawi ◽  
Osama Al-Amer ◽  
...  

The use of insects as a feasible and useful natural product resource is a novel and promising option in alternative medicine. Several components from insects and their larvae have been found to inhibit molecular pathways in different stages of cancer. This study aimed to analyze the effect of aqueous and alcoholic extracts of Vespa orientalis larvae on breast cancer MCF7 cells and investigate the underlying mechanisms. Our results showed that individual treatment with 5% aqueous or alcoholic larval extract inhibited MCF7 proliferation but had no cytotoxic effect on normal Vero cells. The anticancer effect was mediated through (1) induction of apoptosis, as indicated by increased expression of apoptotic genes (Bax, caspase3, and p53) and decreased expression of the anti-apoptotic gene Bcl2; (2) suppression of intracellular reactive oxygen species; (3) elevation of antioxidant enzymes (CAT, SOD, and GPx) and upregulation of the antioxidant regulator Nrf2 and its downstream target HO-1; (4) inhibition of migration as revealed by in vitro wound healing assay and downregulation of the migration-related gene MMP9 and upregulation of the anti-migratory gene TIMP1; and (5) downregulation of inflammation-related genes (NFκB and IL8). The aqueous extract exhibited the best anticancer effect with higher antioxidant activities but lower anti-inflammatory properties than the alcoholic extract. HPLC analysis revealed the presence of several flavonoids and phenolic compounds with highest concentrations for resveratrol and naringenin in aqueous extract and rosmarinic acid in alcoholic extract. This is the first report to explain the intracellular pathway by which flavonoids and phenolic compounds-rich extracts of Vespa orientalis larvae could induce MCF7 cell viability loss through the initiation of apoptosis, activation of antioxidants, and inhibition of migration and inflammation. Therefore, these extracts could be used as adjuvants for anticancer drugs and as antioxidant and anti-inflammatory agents.


2017 ◽  
Vol 45 (14) ◽  
pp. 3345-3350 ◽  
Author(s):  
Geoffrey D. Abrams ◽  
Wenteh Chang ◽  
Jason L. Dragoo

Background: A variety of medications are administered to the intra-articular space for the relief of joint pain. While amide-type local anesthetics have been extensively studied, there is minimal information regarding the potential chondrotoxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid medications. Purpose: To investigate the in vitro chondrotoxicity of single-dose equivalent concentrations of ketorolac, morphine, meperidine, and fentanyl on human chondrocytes. Study Design: Controlled laboratory study. Methods: Human cartilage was arthroscopically harvested from the intercondylar notch and expanded in vitro. Gene expression of cultured chondrocytes before treatment was performed with quantitative polymerase chain reaction for type I collagen, type II collagen, aggrecan, and SOX9. Chondrocytes were then exposed to 0.01%, 0.02%, and 0.04% morphine sulfate; 0.3% and 0.6% ketorolac tromethamine; 0.5%, 1.0%, and 1.5% meperidine hydrochloride; 0.0005% and 0.001% fentanyl citrate; and saline. A custom bioreactor was used to constantly deliver medications, with the dosage of each medication and the duration of exposure based on standard dose equivalents, medication half-lives, and differences in the surface area between the 6-well plates and the native joint surface. After treatment, a live/dead assay was used to assess chondrocyte viability and if minimal cell death was detected. A subset of samples after treatment was maintained to analyze for possible delayed cell death. Results: All tested concentrations of ketorolac and meperidine caused significantly increased cell death versus the saline control, demonstrating a dose-response relationship. The morphine and fentanyl groups did not show increased chondrotoxicity compared with the saline group, even after 2 weeks of additional culture. Conclusion: In vitro exposure of chondrocytes to single-dose equivalent concentrations of either ketorolac or meperidine demonstrated significant chondrotoxicity, while exposure to morphine or fentanyl did not lead to increased cell death.


Author(s):  
JAMES P. FARESE ◽  
JENNA ASHTON ◽  
ROWAN MILNER ◽  
LINDA-LEE AMBROSE ◽  
JAMES VAN GILDER

2021 ◽  
Vol 12 ◽  
Author(s):  
Rodrigo Cuiabano Paes Leme ◽  
Raquel Bandeira da Silva

It has been demonstrated that some non-steroidal anti-inflammatory drugs (NSAIDs), like acetylsalicylic acid, diclofenac, and ibuprofen, have anti-biofilm activity in concentrations found in human pharmacokinetic studies, which could fuel an interest in repurposing these well tolerated drugs as adjunctive therapies for biofilm-related infections. Here we sought to review the currently available data on the anti-biofilm activity of NSAIDs and its relevance in a clinical context. We performed a systematic literature review to identify the most commonly tested NSAIDs drugs in the last 5 years, the bacterial species that have demonstrated to be responsive to their actions, and the emergence of resistance to these molecules. We found that most studies investigating NSAIDs’ activity against biofilms were in vitro, and frequently tested non-clinical bacterial isolates, which may not adequately represent the bacterial populations that cause clinically-relevant biofilm-related infections. Furthermore, studies concerning NSAIDs and antibiotic resistance are scarce, with divergent outcomes. Although the potential to use NSAIDs to control biofilm-related infections seems to be an exciting avenue, there is a paucity of studies that tested these drugs using appropriate in vivo models of biofilm infections or in controlled human clinical trials to support their repurposing as anti-biofilm agents.


2021 ◽  
Author(s):  
Sven Fengler ◽  
Birgit Kurkowsky ◽  
Sanjeev Kumar Kaushalya ◽  
Wera Roth ◽  
Philip Denner ◽  
...  

Optimizing drug candidates for blood-brain barrier (BBB) penetration in humans remains one of the key challenges and many devastating brain diseases including neurodegenerative diseases still do not have adequate treatments. So far, it has been difficult to establish state-of-the-art human stem cell derived in vitro models that mimic physiological barrier properties including a 3D microvasculature in a format that is scalable enough to screen drugs for BBB penetration in early drug development phases. To address this challenge, we established human induced pluripotent stem cell (iPSC)-derived brain endothelial microvessels in a standardized and scalable multi-well plate format. iPSC-derived brain microvascular endothelial cells (BMECs) were supplemented with primary cell conditioned media and grew to intact microvessels in 10 days of culturing. Produced microvessels show a typical BBB phenotype including endothelial protein expression, tight-junctions and polarized localization of efflux transporter. Microvessels exhibited physiological relevant trans-endothelial electrical resistance (TEER), were leak tight for 10 kDa dextran-Alexa 647 and strongly limited the permeability of sodium fluorescein (NaF). Permeability tests with reference compounds confirmed the suitability of our model as platform to identify potential BBB penetrating anti-inflammatory drugs. In summary, the here presented brain microvessel platform recapitulates physiological properties and allows rapid screening of BBB permeable anti-inflammatory compounds that has been suggested as promising substances to cure so far untreatable neurodegenerative diseases.


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