Effects of low molecular weight hyaluronan combined with carprofen on canine osteoarthritis articular chondrocytes and cartilage explants in vitro

Euppayo, Thippaporn; Siengdee, Puntita; Buddhachat, Kittisak; Pradit, Waranee; Viriyakhasem, Nawarat; Chomdej, Siriwadee; Ongchai, Siriwan; Harada, Yasuji; Nganvongpanit, Korakot

doi:10.1007/s11626-015-9908-9

Cited by 15 publications

(9 citation statements)

References 34 publications

(29 reference statements)

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“…However, in this study, it was found that the combination treatment with CAR with HA (Comb24 and Comb48) did not decrease chondrotoxicity (and did not increase chondrocyte viability). Similar to our previous study involving OA chondrocyte cultures, co-treatment with HA did not decrease chondrotoxicity caused by CAR (Euppayo et al, 2015), triamcinolone acetonide (Euppayo et al, 2016), dexamethasone (Siengdee et al, 2015) and prednisolone (Siengdee et al, 2015). However, some studies have shown that HA could reduce cytotoxicity on chondrocyte viability after cells were exposed to bupivacaine (Onur, Sitron & Dang, 2013), indomethacin (Hashizume & Mihara, 2009), dexamethasone (Hashizume & Mihara, 2009) and celecoxib (Hashizume & Mihara, 2009).…”

Section: Discussionsupporting

confidence: 83%

“…However, HA could lessen the side effects of fluoroquinolones when treatment was given in conjunction with those other drugs (Siengdee et al, 2016). On the contrary, the therapeutic effects of HA could not mitigate the side effects of carprofen (Euppayo et al, 2015), corticosteroid (Siengdee et al, 2015) and triamcinolone acetonide (Euppayo et al, 2016) when subjects were treated with HA at the same time.…”

Section: Introductionmentioning

confidence: 99%

“…However, an adverse effect of CAR on cell survival and proteoglycan synthesis has been identified. Additionally, the induction of hepatic toxicosis in dogs as hepatocellular necrosis, lytic necrosis, and apoptosis can result in a decrease in cell viability in canine chondrocyte cultures (Euppayo et al, 2015). Meanwhile, CAR was found to induce oxidative stress in the mitochondria of the colonic mucosa of dogs (Snow et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Post-treatment of hyaluronan to decrease the apoptotic effects of carprofen in canine articular chondrocyte culture

Nganvongpanit

Euppayo

Siengdee

et al. 2020

PeerJ

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A major concern associated with the use of drugs is their adverse side effects. Specific examples of the drugs of concern include antibiotic agents and non-steroidal anti-inflammatory drugs. Despite the presence of a high degree of efficacy for specific conditions, these drugs may deteriorate the surrounding tissues that are exposed to them. Often, carprofen is used for joint inflammation; however, it may stimulate cartilage degradation which can then lead to osteoarthritis progression. In this study, hyaluronan was combined with carprofen treatment in three different applications (pre-treatment, co-treatment and post-treatment) on normal canine chondrocytes to determine whether Hyaluronan (HA) is capable of mitigating the degree of chondrotoxicity of carprofen. Our findings revealed that carprofen at IC20 (0.16 mg/mL) decreased viability and increased nitric oxide (NO) production. Importantly, carprofen induced the apoptosis of canine chondrocytes via the up-regulation of Bax, Casp3, Casp8, Casp9 and NOS2 as compared to the control group. Although the co-treatment of HA and carprofen appeared not to further alleviate the chondrotoxicity of carprofen due to the presence of a high number of apoptotic chondrocytes, post-treatment with HA (carprofen treatment for 24 h and then changed to HA for 24 h) resulted in a decrease in chondrocyte apoptosis by the down-regulation of Bax, Casp3, Casp8, Casp9, NOS2, along with NO production when compared with the treatment of carprofen for 48 h (P < 0.05). These results suggest that HA can be used as a therapeutic agent to mitigate the degree of chondrotoxicity of carprofen.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Post-treatment of hyaluronan to decrease the apoptotic effects of carprofen in canine articular chondrocyte culture

Nganvongpanit

Euppayo

Siengdee

et al. 2020

PeerJ

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“…Moreover, treatment with HA can activate normal chondrocytes to increase the expression of ACAN , which is a key matrix molecule of cartilage, concomitant with upregulation of inhibitors of the matrix‐destructive enzyme TIMP1 and downregulation of MMP3 , a critical matrix‐degrading enzyme. This evidence suggests that HA has a protective effect on primary canine chondrocytes, similar to other reports (Julovi et al ., ; Peng et al ., ; Euppayo et al ., ). Co‐treatment with HA and Enro was successful in increasing s‐GAG production, which may reflect new matrix synthesis.…”

Section: Discussionmentioning

confidence: 99%

Two fluoroquinolones and their combinations with hyaluronan: comparison of effects on canine chondrocyte culture

Siengdee

Euppayo

Buddhachat

et al. 2016

Vet Pharm & Therapeutics

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Fluoroquinolones (FQs) are frequently used for septic arthritis. Increased antibacterial activity has been associated with mammalian cell cytotoxicity that may increase the risk of developing osteoarthritis. This study compared the direct effects of two different FQs, enrofloxacin (Enro) and marbofloxacin (Mar), on normal primary canine chondrocytes and inflammatory-stimulated chondrocytes, in addition to their administration in combination with hyaluronan (HA). Cell viability, cell apoptosis, s-GAG production, and expression patterns of inflammatory, extracellular matrix (ECM) component and protease genes were measured. Enro co-culturing with HA could modify s-GAG synthesis compared with the negative control group. Co-treatment with both FQs and HA significantly decreased cell viability and induced more total apoptotic cell death compared with the negative control and pre-IL-1β-stimulated group. Enro regulated IL-1β-stimulated cells to overexpress IL-1β, TNF, and MMP3, whereas Mar induced upregulation of PTGS2 and NFKB1 and enhanced the expression of ECM component genes HAS1, COL2A1, and ACAN as well as TIMP1 and MMP9. Simultaneous use of HA with Enro can effectively reduce the expression of IL-1β, TNF, and MMP3 in pre-IL-1β-stimulated chondrocytes. These results suggest the beneficial effects of HA in reducing the adverse effects of Enro treatment at the transcriptional level.

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“…Part III, in vitro studies — There were five studies [ 22 , 23 , 38 – 40 ], including anabolic gene ( ACAN and COL2A1 ) expression, catabolic gene ( ADAMTS5 , COX-2 , IL-1β , MMP2 , MMP3 , and MMP13 ) expression, and GAG remaining in chondrocyte pellets or cartilage explants.…”

Section: Resultsmentioning

confidence: 99%

Effects of hyaluronic acid combined with anti-inflammatory drugs compared with hyaluronic acid alone, in clinical trials and experiments in osteoarthritis: a systematic review and meta-analysis

Euppayo¹,

Punyapornwithaya²,

Chomdej³

et al. 2017

BMC Musculoskelet Disord

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BackgroundThe objectives are to compare the efficacy of intra-articular hyaluronic acid (IA-HA) alone and in combination with anti-inflammatory drugs (IA-HA + AI), corticosteroids (CS) or non-steroidal anti-inflammatory drugs (NSAIDs) in clinical trials and in vivo and in vitro studies of osteoarthritis (OA).MethodsData in the BIOSIS, CINAHL, Cochrane Library, EMBASE and Medline databases were collected and analyzed. Random effects models were used to compute the effect size (ES) of the mean difference in pain reduction scores from baseline and the relative risk (RR) of adverse events. The ES of histological scores in vivo and cartilage metabolism in vitro were also calculated. We conducted sensitivity analysis of blinding and intention-to-treat (ITT), compared IA-HA combined with CS vs. IA-HA alone in trials, and compared the effects of HA + AI vs. AI alone in vitro, including anabolic and catabolic gene expression.ResultsThirteen out of 382 papers were included for data analysis. In clinical trials, the ES of pain reduction scores within the 1st month was −4.24 (−6.19, −2.29); 2nd–12th month, −1.39 (−1.95, −0.82); and within one year, −1.63 (−2.19, −1.08), favoring IA-HA + AI (P < 0.001). The ES of RR was 1.08 (0.59, 1.98), and histological scores was 1.38 (−0.55, 3.31). The ES of anabolic gene expression was 1.22 (0.18, 2.25), favoring HA alone (P < 0.05); catabolic gene expression was 0.74 (−0.44, 1.53), favoring HA alone; and glycosaminoglycans remaining was −2.45 (−5.94, 1.03).ConclusionsIA-HA + AI had greater efficacy for pain relief than IA-HA alone within a one-year period. However, HA + AI down-regulated the ACAN gene when compared with HA alone in vitro.

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Effects of low molecular weight hyaluronan combined with carprofen on canine osteoarthritis articular chondrocytes and cartilage explants in vitro

Cited by 15 publications

References 34 publications

Post-treatment of hyaluronan to decrease the apoptotic effects of carprofen in canine articular chondrocyte culture

Post-treatment of hyaluronan to decrease the apoptotic effects of carprofen in canine articular chondrocyte culture

Two fluoroquinolones and their combinations with hyaluronan: comparison of effects on canine chondrocyte culture

Effects of hyaluronic acid combined with anti-inflammatory drugs compared with hyaluronic acid alone, in clinical trials and experiments in osteoarthritis: a systematic review and meta-analysis

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