CIPROFLOXACIN INDUCED CHONDROTOXICITY AND TENDINOPATHY

Elias Adikwu ,Barnaby Nelson

doi:10.3844/ajptsp.2012.94.100

Elias Adikwu , Barnaby Nelson

Open Access

https://doi.org/10.3844/ajptsp.2012.94.100

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Abstract

Ciprofloxacin is one of the fluoroquinolones with a wide clinical acceptability. Rescently there are increasing reports on Ciprofloxacin induce Chondrotoxicity and Tendinopathy in Animal experiment and clinical experience which is of great clinical concern. A comprehensive survey and review of literaure on reported ciprofloxacin induced Chondrotoxicity and Tendinopathy in Humans and Animals was performed. It was observd that ciprofloxacin is a potential inducer of Chrondrotoxicity and Tendinopathy which could be potentiated by coadministration with corticosteroids.This conditions were reported to be characterised by cartilage lesion, matrix swelling, inhibition of chondrocytes proliferation, secretion of soluble proteoglycan, modification of the metabolism and integrity of extracellular proteins, decrease in epiphyseal growth plate, humerus and femur.The mechanism behind this phenomenon is said to be multifactoral. Ciprofloxacin induced Chrondrotoxicity and Tendinopathy in growing animals is attributed to oxidative stress (lipid peroxidation, Deoxyribonucleic Acid (DNA) oxidative stress). Ciprofloxacin induced cartilage damage may also be attributed to formation of Ciprofloxacin chelates and complexes which possesses the potential to induce a deficiency of functionally available divalent ions resulting in cytoskeletal changes. Animal studies showed that oxidative damage or metabolism of tissues was also found suggesting the involvement of a reactive oxygen species. Administration of magnesium, zinc chloride and vitamin E (α tocopherol) were found to prevent or reverse ciprofloxacin induced Chrondrotoxicity and Tendinopathy. Through excess formation of collagen, increase osteoblastic activity, increase bone growth, inhibition of free oxidation radicals’ formation thereby preventing DNA oxidation and oxidative stress. Zinc also directly stimulates DNA synthesis either by enzyme stimulation or altering, the binding of f1 and f3 histones to DNA so as to affect RNA synthesis. Patient medical history should be considered before Ciprofloxacin recommendation. Coadministration with corticosteroid should be done with caution. Further evaluation of antioxidants effect in Ciprofloxacin induce Chonrotoxicity, Tendinopathy in humans could be of clinical importance as observed in Animal studies.

Highlights

The first Quinolone, nalidixic acid was first isolated as a byproduct of the synthesis of chloroquine in early 1960s (Hall et al, 2011) Later in the 1980s fluorinated derivatives e.g., ciprofloxacin were synthesized (Stahlmann, 2002)
Several cartilage lesions marked by matrix swelling and loss of chondrocytes were observed when 400, 800 and 1200 mg kg−1 of Ciprofloxacin was administered to 4 week-old rats for 7 days consecutively
These reports are at variance with the study of Kashida and Kato (1997), who observed that 200mg and 900 m kg−1 of Ciprofloxacin administered to rats did not induce Achilles tendon toxicity

Summary

INTRODUCTION

The first Quinolone, nalidixic acid was first isolated as a byproduct of the synthesis of chloroquine in early 1960s (Hall et al, 2011) Later in the 1980s fluorinated derivatives e.g., ciprofloxacin were synthesized (Stahlmann, 2002). Ciprofloxacin is a second generation fluoroquinolone with a broad spectrum of antibacterial activity It has a good bioavailability after oral administration, good to excellent tissue penetration and relative safe (Ball and Tillotson, 1995; Papich, 1998). It is very active against wide variety of pathogenic bacteria including some gram-positive and most grain-negative organism (Hooper and Wolfson, 1985). Despite its safe profile there are reported cases of Ciprofloxacin induced chrondrotoxicity, Tendinopathy and tendon rupture in animals and humans (Khaliq and Zhanel 2003; Channa et al, 2008). This study reviews reported Ciprofloxacin induced Chrondrotoxicity, Tendinopathy and tendon rupture in humans and animals due to rising trend

Animal Studies

Human Studies

Pathogenesis