The ultrastructural features of quinolone-induced arthropathy were studied in' the humeral and femoral heads of nine skeletally immature Beagle dogs (3 months old) that were dosed orally with difloxacin at 300 mg/kg body weight and euthanatized 24, 36, or 48 hours later in groups of three. Three age-matched dogs were given a placebo and euthanatized after 48 hours. Mitochondria in chondrocytes had significantly greater cross-sectional areas (P < 0.05) in electron micrographs from dogs euthanatized after 48 hours of treatment than did those in other groups. There was also a significantly greater percentage of chondrocytes with swollen mitochondria in treated dogs than in the controls (P < 0.05). These changes preceded the necrosis observed in some chondrocytes in the dogs of the 48-hour group. Disruption of extracellular matrix was first observed in the pericellular matrix of necrotic chondrocytes, indicating that this change was secondary to the changes in chondrocytes. Fissures within cartilages apparently resulted from the loss of the normal association of proteoglycans with collagen fibrils.
BaileyRRKirkJAPeddieBA:
Norfloxacin-induced rheumatic disease.
NZ Med J96:
590,
1983.
2.
BaileyRRNataleRLintonAL:
Nalidixic acid arthralgia.
Can Med Assoc J107:
604, 607,
1972.
3.
BendeleAMHulmanJFHarveyAKHrubeyPSChandrasekharS:
Passive role of articular chondrocytes in quinolone-induced arthropathy in guinea pigs.
Toxicol Pathol18:
304–312,
1990.
4.
BouissouHCaujolleDCaujolleFMilhaudG:
Toxicologic experimentale-tissue cartilagineux et acide nalidixique.
C R Acad Sci Ser III Sic Vie286:
1743–1746,
1978.
5.
BroomND:
An enzymatically induced structural transformation in articular cartilage. Its significance with respect to matrix breakdown.
Arthritis Rheum31:
210–218,
1988.
6.
BurkhardtJEHillMACarltonWWKestersonJW:
Histologic and histochemical changes in articular cartilages of immature Beagle dogs dosed with difloxacin, a fluoroquinolone.
Vet Pathol27:
162–170,
1990.
7.
CastoraFJVisseringFFSimpsonMV:
The effect of bacterial DNA gyrase inhibitors on DNA synthesis in mammalian mitochondria.
Biochim Biophys Acta740:
417–427,
1983.
8.
ChevilleNF:
Cell Pathology,
2nd ed.,
pp. 75–129.
Iowa State University Press, Ames, IA,
1983.
9.
DingleJTBlowAMJBarrettAJMartinPE:
Proteoglycan-degrading enzymes. A radiochemical assay method and the detection of a new enzyme, cathepsin F.
Biochem J167:
775–785,
1977.
10.
FarnumCEWilsmanNJ:
Pericellular matrix of growth plate chondrocytes: a study using postfixation with os-mium-ferrocyanide.
J Histochem Cytochem31:
765–775,
1983.
11.
GoughABarsoumNJMitchellLMcGuireEJde la IglesiaFA:
Juvenile canine drug-induced arthropathy: clinicopathological studies on articular lesions caused by oxolinic and pipemidic acids.
Toxicol Appl Pharmacol51:
177–187,
1979.
12.
GoughAWBarsoumNJRenlundRCSturgessJMde la IglesiaFA:
Fine structural changes during reparative phase of canine drug-induced arthropathy.
Vet Pathol22:
82–84,
1985.
13.
GoughAWde la IglesiaFA:
A semiquantitative method to evaluate drug-induced juvenile arthropathy in the canine.
Toxicol Pathol7:
6–9,
1979.
14.
HascallGK:
Cartilage proteoglycans: comparison of sectioned and spread whole molecules.
J Ultrastruct Res70:
369–375,
1980.
15.
HeinegardDOldbergA:
Structure and biology of cartilage and bone matrix non-collagenous macromolecules.
Fed Am Soc Exp Biol J3:
2042–2051,
1989.
JeandelCManclauxAMBannwarthBPerePPeninFNetterPCunyG:
Arthritis induced by norfloxacin.
J Rheum16:
560–561,
1989.
19.
KatoMOnoderaT:
Effect of ofloxacin on the uptake of [3H]thymidine by articular cartilage cells in the rat.
Toxicol Lett44:
131–142,
1988.
20.
KatoMOnoderaT:
Morphological investigation of cavity formation in articular cartilage induced by ofloxacin in rats.
Fundam Appl Toxicol11:
110–119,
1988.
21.
KincaidSAVan SickleDCWilsmanNJ:
Histochemical evidence of a functional heterogeneity of the chondrocytes of adult canine articular cartilage.
Histochem J4:
237–243,
1972.
22.
KirbyCP:
Treatment of simple urinary tract infections in general practice with a 3-day course of norfloxacin.
J Antimicrob Chemo13
(Suppl B):
107–112,
1984.
23.
PelletierJMartel-PelletierJMalemudC:
Canine ostoarthritis: effects of endogenous neutral metalloproteoglycanases on articular cartilage proteoglycans.
J Orthop Res6:
379–388,
1988.
24.
ReiterCPfeifferMHullmanRN:
Brief report: safety of ciprofloxacin based upon phase IV studies (“anwendungs-beobachtung”) in the Federal Republic of Germany.
Am J Med87
(Suppl 5A):
103S–106S,
1989.
25.
SchachtPArcieriGHullmanR:
Safety of ciprofloxacin.
Am J Med87(Suppl 5A):98S-102S, 1989.
26.
ShenLLKohlbrennerWEWeiglDBaranowskiJ:
Mechanism of quinolone inhibition of DNA gyrase.
J Biol Chem264:
2973–2978,
1989.
27.
StahlmannRMerkerHJHinzNChahoudIWebbJHegerWNeubertD:
Ofloxacin in juvenile non-human primates and rats. Arthropathia and drug plasma concentrations.
Arch Toxicol64:
193–204,
1990.
28.
TatsumiHSendaHYateraSTakemotoYYamayoshiMOhnishiK:
Toxicological studies on pipemidic acid. V. Effect on diarthrodial joints of experimental animals.
J Toxicol Sci3:
357–367,
1978.
29.
ZanettiMRatcliffeAWattF:
Two subpopulations of differentiated chondrocytes identified with a monoclonal antibody to keratan sulfate.
J Cell Biol101:
53–59,
1985.
