Fluoroquinolone exposure in utero did not affect articular cartilage of resulting foals

Abstract

Background: Recent studies have shown that fluoroquinolones, specifically, enrofloxacin and its active metabolite (ciprofloxacin), cross the equine placenta without causing gross or histological lesions in the first and third trimester fetuses or resulting foal. However, it is possible that in utero exposure to fluoroquinolones may cause subtle lesions not detectable by standard means; thus, a more in-depth assessment of potential toxicity is warranted. Objectives: To use quantitative magnetic resonance imaging (qMRI), biomechanical testing, and chondrocyte gene expression to evaluate the limbs of foals exposed to enrofloxacin during the third trimester of pregnancy. Study design: In vivo and control terminal experiment. Methods: Healthy mares at 280 days gestation were assigned into three groups: untreated (n = 5), recommended therapeutic (7.5 mg/kg enrofloxacin, PO, SID, n = 6) or supratherapeutic (15 mg/kg, PO, SID, n = 6) doses for 14 days. Mares carried and delivered to term and nursed their foals for ~30 days. Two additional healthy foals born from untreated mares were treated post-natally with enrofloxacin (10 mg/kg PO, SID, for 5 days). By 30 days, foal stifles, hocks, elbows, and shoulders were radiographed, foals were subjected to euthanasia, and foal limbs were analysed by quantitative MRI, structural MRI, biomechanical testing and chondrocyte gene expression. Results: Osteochondral lesions were detected with both radiography and structural MRI in foals from both enrofloxacin-treated and untreated mares. Severe cartilage erosions, synovitis and joint capsular thickening were identified in foals treated with enrofloxacin post-natally. Median cartilage T2 relaxation times differed between joints but did not differ between treatment groups. Main limitations: A small sample size was assessed and there was no long-term follow-up. Conclusion: While further research is needed to address long-term foal outcomes, no differences were seen in advanced imaging, biomechanical testing or gene expression by 30 days of age, suggesting that enrofloxacin may be a safe and useful antibiotic for select bacterial infections in pregnant mares.

The Research Status, Potential Hazards and Toxicological Mechanisms of Fluoroquinolone Antibiotics in the Environment

“…For example, ciprofloxacin significantly reduced the hydrophobicity index of the bile acid pool of male Wistar rats, reduced secondary bile acids, and increased taurine-conjugated primary bile acids in both the serum and large intestine compared with moxifloxacin [ 88 ]. Severe cartilage erosions, synovitis, and joint capsular thickening were identified in foals postnatally treated with enrofloxacin, indicating that in utero exposure to FQs may cause subtle lesions [ 89 ]. Tang et al (2017) found that FQ antibiotics were enriched in the dorsal-epaxial muscle of living puffer fish, thus causing health risks for humans [ 90 ].…”

The research status, potential hazards and toxicological mechanisms of fluoroquinolone antibiotics in the environment

“…For example, cipro oxacin signi cantly reduced the hydrophobicity index of the bile acid pool of male Wistar rats, reduced secondary bile acids, and increased taurine-conjugated primary bile acids in both the serum and large intestine compared with moxi oxacin(Wang et al 2020). Severe cartilage erosions, synovitis and joint capsular thickening were identi ed in foals treated with enro oxacin postnatally, indicating that utero exposure to FQs may cause subtle lesions(Ellerbrock et al 2020). Li et al (2018) found that a 125 mg/kg dose of enro oxacin induced catalase and glutathione peroxidase and increased CYP450 content in pig liver microsomes.Twenty-ve and 125 mg/kg doses of enro oxacin elevated the activity of microsomal NADPHcytochrome C reductase Tang et al (2017).…”