Chondrotoxicity and Toxicokinetics of Sparfloxacin in Juvenile Rats

ABSTRACT Sparfloxacin is a fluoroquinolone with improved antibacterial activity against gram-positive pathogens. Like other quinolones, use of this drug is contraindicated in children and adolescents because of its potential chondrotoxicity in juveniles. We performed histological and immunohistochemical studies on the knee joint cartilage in 5-week-old rats after treatment with 600 or 1,800 mg of sparfloxacin/kg of body weight. Treatment with single or multiple oral doses of 600 mg of sparfloxacin/kg was not sufficient to induce joint cartilage lesions. However, five of eight rats treated with a single oral dose of 1,800 mg of sparfloxacin/kg of body weight showed typical cartilage lesions in the femoral part of the knee joint. The concentrations of the drug in plasma measured 0.25, 0.75, 1.5, 3, 6, 12, and 24 h after the administration of an oral dose of 600 mg of sparfloxacin/kg were 6.3 ± 1.8, 9.2 ± 1.7, 9.6 ± 2.7, 13.0 ± 1.8, 12.3 ± 1.6, 3.4 ± 0.4, and 0.30 ± 0.20 mg/liter, respectively (mean ± standard deviation [SD];n = 5 to 6 per group). The concentrations in plasma measured 0.75, 1.5, 3, 6, 24, and 48 h after the administration of an oral dose of 1,800 mg of sparfloxacin/kg were 10.9 ± 1.5, 15.9 ± 1.6, 19.1 ± 1.7, 14.9 ± 3.1, 4.1 ± 0.6, and 0.46 ± 0.37 mg/liter, respectively (mean ± SD;n = 3 to 4 per group). The concentrations of sparfloxacin in joint cartilage were significantly higher at all time points studied (114.8 ± 80, 99.4 ± 31.5, 84.9 ± 16.8, 44.4 ± 13.9, and 14.2 ± 4.8 mg of sparfloxacin/kg at 1.5, 3, 6, 24, and 48 h after the administration of 1,800 mg/kg, respectively). The range of concentrations in bone were similar to the range of concentrations in cartilage (peak, 115 ± 12 mg/kg after 3 h). Our data indicate that chondrotoxic doses of sparfloxacin in juvenile rats are approximately 300 times higher than the doses of sparfloxacin used therapeutically (1,800 versus approximately 6 mg/kg of body weight), but due to species differences in kinetics, concentrations in plasma differ by a factor of only approximately 15. More data on quinolone concentrations in cartilage from animals and humans could provide a better basis for a reasonable risk assessment.

Download Full-text

Synergistic Effect of Ofloxacin and Magnesium Deficiency on Joint Cartilage in Immature Rats

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.6.1755-1759.2002 ◽

2002 ◽

Vol 46 (6) ◽

pp. 1755-1759 ◽

Cited By ~ 10

Author(s):

Edith Lozo ◽

Kai Riecke ◽

Rudolf Schwabe ◽

Jürgen Vormann ◽

Ralf Stahlmann

Keyword(s):

Synergistic Effect ◽

Magnesium Deficiency ◽

Peak Plasma ◽

Pediatric Population ◽

Standard Diet ◽

Joint Cartilage ◽

Deficient Diet ◽

Cartilage Lesions ◽

Oral Doses ◽

And Cartilage

ABSTRACT Single high oral doses of fluoroquinolones (e.g., 1,200 mg of ofloxacin/kg of body weight) are chondrotoxic in juvenile rats. Characteristic cartilage lesions are detectable as early as 12 h after treatment. Since this dosing regimen does not reflect the therapeutic situation, we studied the effects of a 5- or 7-day treatment with ofloxacin at lower oral doses (10, 30, and 100 mg/kg twice a day [b.i.d.]) on joint cartilage in 4-week-old rats. We additionally investigated whether the effects of ofloxacin under these conditions are enhanced in animals kept on a magnesium-deficient diet during treatment. Knee joints were examined histologically. The concentrations of ofloxacin and magnesium were determined in plasma and cartilage. The lowest ofloxacin dose at which cartilage lesions occurred in animals on a standard diet was 100 mg/kg b.i.d. for 5 days. Peak plasma ofloxacin levels were approximately 10 mg/liter in these rats and thus were in the same range as the levels in the plasma of humans during therapy with high doses of ofloxacin. Treatment with 30 mg of ofloxacin/kg b.i.d. for 7 days caused no cartilage lesions in rats on a standard diet, but lesions did occur in 10 of 12 rats that were simultaneously fed a magnesium-deficient diet. Magnesium concentrations in bone, plasma, and cartilage from animals on an Mg2+-deficient diet were significantly lower than those in the controls. The concentration in plasma from animals on an Mg2+-deficient diet was 0.27 ± 0.03 mmol/liter, whereas it was 0.88 ± 0.08 mmol/liter in plasma from rats on a standard diet (means ± standard deviations). Ofloxacin treatment did not change the total magnesium concentrations in tissues, as determined with ashed samples. The incidence of ofloxacin-induced lesions was higher in the magnesium-deficient animals, suggesting a synergistic effect. These results must be taken into account for a benefit-risk evaluation if ofloxacin is considered for use in the pediatric population.

Download Full-text

Effects of the Des-F(6)-Quinolone Garenoxacin (BMS-284756), in Comparison to Those of Ciprofloxacin and Ofloxacin, on Joint Cartilage in Immature Rats

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.10.3320-3322.2002 ◽

2002 ◽

Vol 46 (10) ◽

pp. 3320-3322 ◽

Cited By ~ 15

Author(s):

Eva Maria Kappel ◽

Mehdi Shakibaei ◽

Akintunde Bello ◽

Ralf Stahlmann

Keyword(s):

Body Weight ◽

Peak Plasma ◽

Joint Cartilage ◽

Once Daily ◽

Cartilage Lesions ◽

Human Risk ◽

Immature Rats ◽

Pediatric Use

ABSTRACT We did not observe signs of chondrotoxicity in immature rats treated orally with garenoxacin (BMS-284756) at doses up to five times 600 mg/kg of body weight or with ciprofloxacin, whereas ofloxacin induced typical cartilage lesions. The peak plasma garenoxacin concentration was 25.5 mg/liter after administration of a dose of 600 mg/kg once daily for 5 days. Assuming that this model is predictive of human risk, BMS-284756 and ciprofloxacin should be more suitable for pediatric use than ofloxacin.

Download Full-text

Obesity Factors on The Incidence of Joint Pain of Elderly

Jurnal Ners dan Kebidanan (Journal of Ners and Midwifery) ◽

10.26699/jnk.v8i2.art.p206-210 ◽

2021 ◽

Vol 8 (2) ◽

pp. 206-210

Author(s):

Eny Masruroh ◽

Erry Setyadhani

Keyword(s):

Body Weight ◽

Knee Joint ◽

Joint Pain ◽

Cartilage Damage ◽

The Elderly ◽

The Body ◽

Bivariate Analysis ◽

Physical Aspect ◽

Excess Body Weight ◽

Joint Cartilage

Aging is a process that will be experienced by humans according to the cycle of growth and development. Changes both physically and psychologically often cause disorders and health problems that must be resolved. Problems with the physical aspect of the elderly, one of which is a decrease in musculoskeletal function, especially in the joints, often manifest the appearance of joint pain. The presence of joint cartilage damage due to inflammation, as well as an increase in the load on the joints due to excess body weight (obesity) is other factors that often arise. The hip, lumbal, cervical and knee joints are the parts that support the body's weight, so they experience the most problems. The purpose of this study was to determine the correlation between obesity and the incidence of knee joint pain in the elderly. The design of the study was correlational analytic with a cross sectional approach. The sampling was purposive sampling with 50 respondents as the sample. The instrument used was an observation sheet to measure the respondent's obesity variable and to determine the presence of joint pain using an interview form. The measurement results were then processed and bivariate analysis was carried out using the chi square test. The results of the research analysis Showed the value of p = 0.004 and α = 0.05, this meant that p < 0.05, so there was a correlation between the level of obesity and the occurrence of joint pain. This was because not only age but also increasing body weight cause joint paint. The ability of the knee joint to support the body as a whole was getting heavier due to friction of the joint cartilage. From these studies, it can be concluded that in the elderly, excess body weight can affect to the ability of bones and joints and result in joint pain. The health workers should support the elderly so that the elderly avoid the stress.

Download Full-text

Magnesium deficiency induces joint cartilage lesions in juvenile rats which are identical to quinolone-induced arthropathy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.39.9.2013 ◽

1995 ◽

Vol 39 (9) ◽

pp. 2013-2018 ◽

Cited By ~ 57

Author(s):

R. Stahlmann ◽

C. Forster ◽

M. Shakibaei ◽

J. Vormann ◽

T. Gunther ◽

...

Keyword(s):

Magnesium Deficiency ◽

Joint Cartilage ◽

Juvenile Rats ◽

Cartilage Lesions

Download Full-text

Knee joint cartilage visualization and quantification in normal and osteoarthritis

2010 International Conference on Systems in Medicine and Biology ◽

10.1109/icsmb.2010.5735360 ◽

2010 ◽

Cited By ~ 4

Author(s):

M. S. Mallikarjuna Swamy ◽

M. S. Holi

Keyword(s):

Knee Joint ◽

Joint Cartilage

Download Full-text

Toxic effect and oral acute LD50 study of Nerium oleander in male guineapigs

Bangladesh Journal of Veterinary Medicine ◽

10.3329/bjvm.v2i2.2562 ◽

1970 ◽

Vol 2 (2) ◽

pp. 159-161 ◽

Cited By ~ 1

Author(s):

MGA Chowdhury ◽

A Azizunnesa ◽

MA Hossain ◽

ML Rahman ◽

Q Hasan

Keyword(s):

Body Weight ◽

Abdominal Pain ◽

Oral Dose ◽

Respiratory Distress ◽

Toxic Effect ◽

Single Oral Dose ◽

Nerium Oleander ◽

Male Adult ◽

Experimental Animals ◽

Group A

The toxic effect of Nerium oleander was studied in 36 male adult guineapigs during the period from July to December 1994. These 36 animals were divided into six equal groups (A to F), each consisting of six animals. Each animal of groups B to F was administered with a single oral dose of crude watery extract of sheath oleander @ 300, 450, 600, 750 and 900 mg / kg body weight, respectively whereas animals of group A served as control. Each of the experimental animals was carefully observed and the toxic signs recorded as nausea, anorexia, dullness, depression, restlessness, abdominal pain, salivation, reluctant to move, tremor, resting of chin on the ground, respiratory distress, paralysis of the limbs, recumbency, convulsion followed by death with characteristic groaning. It may be concluded that the lowest dose 300 mg / kg body weight is non lethal to the male guineapigs and the dose of 450, 600, 750 and 900 mg / kg body weight caused 17%, 50%, 83% and 100% mortality, respectively and the LD50 is 540 mg / kg body weight.Key words: Nerium oleander; toxic signs; oral acute LD50; guineapigsdoi: 10.3329/bjvm.v2i2.2562Bangl. J. Vet. Med. (2004). 2 (2): 159-161

Download Full-text

Light and electron microscopical immunohistochemical localization of the small proteoglycan core proteins decorin and biglycan in human knee joint cartilage

The Histochemical Journal ◽

10.1007/bf02388571 ◽

1994 ◽

Vol 26 (12) ◽

pp. 939-945 ◽

Cited By ~ 45

Author(s):

N. Miosge ◽

K. Flachsbart ◽

W. Goetz ◽

W. Schultz ◽

H. Kresse ◽

...

Keyword(s):

Knee Joint ◽

Immunohistochemical Localization ◽

Joint Cartilage ◽

Human Knee ◽

Human Knee Joint ◽

Core Proteins ◽

Electron Microscopical ◽

Small Proteoglycan

Download Full-text

Increase in Cell Number as a Factor in the Growth of the Organs and Tissues of the Young Male Rat

Development ◽

10.1242/dev.10.4.530 ◽

1962 ◽

Vol 10 (4) ◽

pp. 530-562

Author(s):

M. Enesco ◽

C. P. Leblond

Keyword(s):

Body Weight ◽

Weight Gain ◽

Room Temperature ◽

Young Male ◽

Cell Number ◽

The Body ◽

Male Rat ◽

The Past ◽

Old Rats ◽

Young Rat

While the organs and tissues of the young rat are known to increase in size with age (Donaldson, 1924), little is known of the role played by the component cells in this increase. There is evidence that cells enlarge (Levi, 1906; Plenk, 1911) and new cells are added (Strasburger, 1893), but we do not know to what extent the enlargement and proliferation of the cells cause the growth of organs and tissues. The present work is an attempt to clarify this problem. In the past, the growth of organs and tissues has often been measured by weight gain (Donaldson, 1924). However, this approach might be misleading, since the body-weight may increase in the absence of growth, for instance as a result of fat-storage in old rats, of pregnancy in females, and even of changes in room temperature.

Download Full-text

Effects of Body Weight Modification on Internal Knee Contact Forces During Gait

Volume 1A: Abdominal Aortic Aneurysms; Active and Reactive Soft Matter; Atherosclerosis; BioFluid Mechanics; Education; Biotransport Phenomena; Bone, Joint and Spine Mechanics; Brain Injury; Cardiac Mechanics; Cardiovascular Devices, Fluids and Imaging; Cartilage and Disc Mechanics; Cell and Tissue Engineering; Cerebral Aneurysms; Computational Biofluid Dynamics; Device Design, Human Dynamics, and Rehabilitation; Drug Delivery and Disease Treatment; Engineered Cellular Environments ◽

10.1115/sbc2013-14727 ◽

2013 ◽

Author(s):

Allison L. Kinney ◽

Heather K. Vincent ◽

Melinda K. Harman ◽

James Coburn ◽

Darryl D. D’Lima ◽

...

Keyword(s):

Body Weight ◽

Risk Factor ◽

Knee Joint ◽

Inverse Dynamics ◽

Contact Forces ◽

Weight Changes ◽

Body Weight Changes ◽

Total Knee ◽

Knee Joint Loading ◽

Knee Load

Obesity is commonly considered a risk factor for the development of knee osteoarthritis [1]. Previous studies have shown that reductions in body weight correspond to reductions in total knee joint compressive forces (as calculated by inverse dynamics) [2–4]. A recent study showed that external knee load measurements are not strong predictors of internal knee contact forces [5]. Therefore, direct measurement of knee contact force is important for understanding how body weight changes impact knee joint loading. Force-measuring knee implants can directly measure internal knee contact forces [6].

Download Full-text