Comparison of the effects of cefazolin and ceftriaxone on canine chondrocyte culture

Abstract

Cephalosporins (CEFs) are antibiotics frequently used to treat bone infections and septic arthritis. The effects of CEFs on chondrocytes have not been studied until now. Cefazolin (cef1) and ceftriaxone (cef3), first-and third-generation CEFs, were selected to investigate their direct effects on normal and osteoarthritic (OA) primary canine chondrocytes, which were either nonstimulated or stimulated with the pro-inflammatory cytokine IL-1β. In our results, treatment with CEFs increased the negative effects on both conditioned normal and OA chondrocytes, especially when applied to IL-1β-stimulated cells (inflammatory stimulus). CEFs significantly decreased cell viability and induced apoptotic cell death in both normal and OA chondrocytes; moreover, treatment with cef1 caused necrotic cell death in OA chondrocytes. Cef3 treatment could increase s-GAG synthesis in normal cells preincubated with IL-1β, while cef1 had no significant effect. The expression of TNF was clearly downregulated after cef3 treatments, whereas it was upregulated after cef1 treatments. However, cef3 induced stronger downregulation of TIMP1 and the extracellular matrix component genes COL2A1 and ACAN. In conclusion, these results suggest both the cytotoxic effects of CEFs and their adverse effects on chondrogenic marker genes at the transcriptional level, which provide additional insight into the clinical application of cef1 and cef3.

Review of Intra-Articular Use of Antibiotics and Antiseptic Irrigation and Their Systematic Association with Chondrolysis

“…From the four included studies on the cephalosporin class, cefazolin doses ranging from 0.39 to 50 mg/mL demonstrated dose-dependent chondrotoxicity. 20,26,28 Ceftazidime in doses ranging from 0.39 to 25 mg/mL also demonstrated dose-dependent chondrotoxicity. 20,26 Although Gunal et al 29 did not find ceftriaxone to be chondrotoxic in a leporine model, they did not report a dosage used.…”

“…In addition, ceftriaxone at 4.17 -50 mg/mL in a canine model did demonstrate dose-dependent chondrotoxicity. 28 Aminoglycosides. Four out of the eight aminoglycoside studies assessed amikacin, which demonstrated dose-dependent chondrotoxicity in canine and equine models.…”

Sefazolinin değişen dozlarının in vitro 3T3-Fare fibroblast kültürü üzerine etkisi

“…Sonuçlarımız, bakterisit olarak etkin doz olan 100 µg/ml'nin oldukça üzerinde kalan 250 µg/ml ve 500 µg/ml doz aralığında dahi sefazolin kullanımının, fibroblast hücrelerinin çoğalma hızı üzerinde negatif bir etkisi olmadığını ortaya koymaktadır. (18). Çalışmamızda ayrıca sefazolinin 500 µg/ml olarak uygulandığı gruplarda oksidatif stresi az da olsa arttırdığı gözlemlense de bu artış istatistiksel olarak anlamlı değildi ve literatürde bu verimizi destekleyecek başka bir yayına da rastlamadık.…”

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

“…Several drugs, such as local anesthetic drugs (10 mg/mL of lidocaine or 7.5 mg/mL of ropivacaine in human chondrocyte culture), corticosteroids (25 mm of dextramethasone, 25 mg/mL of prednisolone or 7 mg/mL of betamethasone in human chondrocyte culture), cefazolin (2.0-3.33 mg/mL in canine chondrocyte culture) and fluoroquinolones (182 mg/mL of enrofloxacin or 295 mg/mL of marbofloxacin), have been shown to produce adverse effects on articular cartilage including apoptosis and the inhibition of growth of chondrocyte cells (Chrysis et al, 2005;Farkas et al, 2010;Nakazawa et al, 2002;Siengdee et al, 2016;Siengdee et al, 2017). This phenomenon can result in a loss of extra-cellular matrix formation and the progressive degradation of articular cartilage (Farkas et al, 2010).…”

“…This phenomenon can result in a loss of extra-cellular matrix formation and the progressive degradation of articular cartilage (Farkas et al, 2010). For example, antibiotics such as cefazolin (2.0-3.33 mg/mL) may cause apoptosis and necrosis of chondrocytes by inducing the alpha tumor necrosis factor (TNF-a) and matrix metelloproteinase (MMP) production, decreasing the expression of key matrix molecules of the cartilage encoded by aggrecan (ACAN) and type II collagen COL2A1, and by downregulating the tissue inhibitors of the matrix metalloproteinase-1 (TIMP1) (Siengdee et al, 2017). Fluoroquinolone treatment has also been widely associated with certain side effects, including the development of severe musculoskeletal disorders, for example, tendinitis and tendon ruptures in humans after a 1-week course of ciprofloxacin, 250 mg twice daily (Akali & Niranjan, 2008), cartilage deformities after receiving ofloxacin, 20 mg/kg once daily for 7 consecutive days in 3-month-old male beagle dogs (Yabe et al, 1997), along with the altering of inflammatory mediators and extracellular matrix (ECM) components, as well as the MMP encoding genes in chondrocyte cultures in vitro (Siengdee et al, 2016).…”