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

2002 ◽  
Vol 46 (6) ◽  
pp. 1755-1759 ◽  
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.

scholarly journals Chondrotoxicity and Toxicokinetics of Sparfloxacin in Juvenile Rats

1998 ◽  
Vol 42 (6) ◽  
pp. 1470-1475 ◽  
Author(s):  
Ralf Stahlmann ◽  
Uta Zippel ◽  
Christian Förster ◽  
Rudolf Schwabe ◽  
Mehdi Shakibaei ◽  
...  
Keyword(s):  
Body Weight ◽  
Oral Dose ◽  
Knee Joint ◽  
Species Differences ◽  
Joint Cartilage ◽  
Juvenile Rats ◽  
Cartilage Lesions ◽  
Old Rats ◽  
Immunohistochemical Studies ◽  
Oral Doses

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.

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

2002 ◽  
Vol 46 (10) ◽  
pp. 3320-3322 ◽  
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.

Dietary magnesium deficiency affects gut microbiota and anxiety-like behaviour in C57BL/6N mice

2015 ◽  
Vol 27 (5) ◽  
pp. 307-311 ◽  
Author(s):  
Bettina Pyndt Jørgensen ◽  
Gudrun Winther ◽  
Pernille Kihl ◽  
Dennis S. Nielsen ◽  
Gregers Wegener ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Magnesium Deficiency ◽  
Standard Diet ◽  
Microbiota Composition ◽  
Deficient Diet ◽  
Anxiety Test ◽  
Dietary Magnesium ◽  
Gradient Gel Electrophoresis ◽  
The Impact ◽  
Gut Microbiota Composition

ObjectiveMagnesium deficiency has been associated with anxiety in humans, and rodent studies have demonstrated the gut microbiota to impact behaviour.MethodsWe investigated the impact of 6 weeks of dietary magnesium deficiency on gut microbiota composition and anxiety-like behaviour and whether there was a link between the two. A total of 20 C57BL/6 mice, fed either a standard diet or a magnesium-deficient diet for 6 weeks, were tested using the light-dark box anxiety test. Gut microbiota composition was analysed by denaturation gradient gel electrophoresis.ResultsWe demonstrated that the gut microbiota composition correlated significantly with the behaviour of dietary unchallenged mice. A magnesium-deficient diet altered the gut microbiota, and was associated with altered anxiety-like behaviour, measured by decreased latency to enter the light box.ConclusionMagnesium deficiency altered behavior. The duration of magnesium deficiency is suggested to influence behaviour in the evaluated test.

Dietary magnesium deficiency alters gut microbiota and leads to depressive-like behaviour

2015 ◽  
Vol 27 (3) ◽  
pp. 168-176 ◽  
Author(s):  
Gudrun Winther ◽  
Betina M Pyndt Jørgensen ◽  
Betina Elfving ◽  
Denis Sandris Nielsen ◽  
Pernille Kihl ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Magnesium Deficiency ◽  
Forced Swim Test ◽  
Tolerance Test ◽  
Standard Diet ◽  
Restricted Diet ◽  
Microbial Composition ◽  
Deficient Diet ◽  
Significant Difference ◽  
Dietary Magnesium

ObjectiveGut microbiota (GM) has previously been associated with alterations in rodent behaviour, and since the GM is affected by the diet, the composition of the diet may be an important factor contributing to behavioural changes. Interestingly, a magnesium restricted diet has been shown to induce anxiety and depressive-like behaviour in humans and rodents, and it could be suggested that magnesium deficiency may mediate the effects through an altered GM.MethodsThe present study therefore fed C57BL/6 mice with a standard diet or a magnesium deficient diet (MgD) for 6 weeks, followed by behavioural testing in the forced swim test (FST) to evaluate depressive-like behaviour. An intraperitoneal glucose tolerance test (GTT) was performed 2 day after the FST to assess metabolic alterations. Neuroinflammatory markers were analysed from hippocampus. GM composition was analysed and correlated to the behaviour and hippocampal markers.ResultsIt was found that mice exposed to MgD for 6 weeks were more immobile than control mice in the FST, suggesting an increased depressive-like behaviour. No significant difference was detected in the GTT. GM composition correlated positively with the behaviour of undisturbed C57BL/6 mice, feeding MgD diet altered the microbial composition. The altered GM correlated positively to the hippocampal interleukin-6.ConclusionIn conclusion, we hypothesise that imbalances of the microbiota–gut–brain axis induced by consuming a MgD diet, contributes to the development of depressive-like behaviour.

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

1995 ◽  
Vol 39 (9) ◽  
pp. 2013-2018 ◽  
Author(s):  
R. Stahlmann ◽  
C. Forster ◽  
M. Shakibaei ◽  
J. Vormann ◽  
T. Gunther ◽  
...  
Keyword(s):  
Magnesium Deficiency ◽  
Joint Cartilage ◽  
Juvenile Rats ◽  
Cartilage Lesions

scholarly journals Diminished Ciprofloxacin-Induced Chondrotoxicity by Supplementation with Magnesium and Vitamin E in Immature Rats

2007 ◽  
Vol 51 (3) ◽  
pp. 1022-1027 ◽  
Author(s):  
Kerstin Pfister ◽  
Dago Mazur ◽  
Jürgen Vormann ◽  
Ralf Stahlmann
Keyword(s):  
Vitamin E ◽  
Wistar Rats ◽  
Diet Group ◽  
Standard Diet ◽  
Joint Cartilage ◽  
Cartilage Lesions ◽  
Immature Rats ◽  
Group A ◽  
Group B ◽  
Group D

ABSTRACT Quinolone-induced chondrotoxicity in juvenile rats and multiple other species has been demonstrated previously. Identical damages can be induced in immature rats by feeding them a magnesium-deficient diet. The objective of the present study was to investigate whether, in reverse, oral supplementation with magnesium, vitamin E, or both can diminish the typical quinolone-induced arthropathy in juvenile Wistar rats. Four groups of 12 (6 male, 6 female) 24-day-old Wistar rats were each fed either normal feed (group A), a vitamin E-enriched diet (group B), a magnesium-enriched diet (group C), or a diet enriched with both vitamin E and magnesium (group D) for 10 days. All rats received two subcutaneous ciprofloxacin doses of 600 mg/kg of body weight on postnatal day 32. Two days later, the rats were sacrificed and cartilage samples from knee joints were examined under a light microscope for the presence of typical quinolone-induced joint cartilage lesions. In addition, magnesium, calcium, and vitamin E concentrations in cartilage and plasma were determined. In the samples from rats fed a normal diet (group A), 17 quinolone-induced joint cartilage lesions were observed. In groups fed an enriched diet, the incidence of specific lesions (n) was significantly lower: group B, n = 10 (41% reduction compared to the incidence for group A; P < 0.05); group C, n = 6 (65% reduction; P < 0.01); and group D, n = 3 (82% reduction; P < 0.01). In comparison to the standard diet, diets with magnesium and vitamin E supplementation resulted in significantly higher magnesium and vitamin E concentrations in plasma and articular cartilage. Supplementation with magnesium and vitamin E alone or in combination may relevantly diminish joint cartilage lesions induced by quinolones in immature rats, with an additive effect of combined supplementation. The data further support the proposed pathomechanism of quinolone-induced arthropathy and the crucial role of magnesium in immature joint cartilage.

scholarly journals Magnesium Deficiency Alters Expression of Genes Critical for Muscle Magnesium Homeostasis and Physiology in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2169
Author(s):  
Dominique Bayle ◽  
Cécile Coudy-Gandilhon ◽  
Marine Gueugneau ◽  
Sara Castiglioni ◽  
Monica Zocchi ◽  
...  
Keyword(s):  
Gastrocnemius Muscle ◽  
Magnesium Deficiency ◽  
Mitochondrial Dynamics ◽  
Body Weight Gain ◽  
Whole Body ◽  
Muscle Physiology ◽  
Deficient Diet ◽  
Muscle Weight ◽  
Magnesium Homeostasis ◽  
Expression Of Genes

Chronic Mg2+ deficiency is the underlying cause of a broad range of health dysfunctions. As 25% of body Mg2+ is located in the skeletal muscle, Mg2+ transport and homeostasis systems (MgTHs) in the muscle are critical for whole-body Mg2+ homeostasis. In the present study, we assessed whether Mg2+ deficiency alters muscle fiber characteristics and major pathways regulating muscle physiology. C57BL/6J mice received either a control, mildly, or severely Mg2+-deficient diet (0.1%; 0.01%; and 0.003% Mg2+ wt/wt, respectively) for 14 days. Mg2+ deficiency slightly decreased body weight gain and muscle Mg2+ concentrations but was not associated with detectable variations in gastrocnemius muscle weight, fiber morphometry, and capillarization. Nonetheless, muscles exhibited decreased expression of several MgTHs (MagT1, CNNM2, CNNM4, and TRPM6). Moreover, TaqMan low-density array (TLDA) analyses further revealed that, before the emergence of major muscle dysfunctions, even a mild Mg2+ deficiency was sufficient to alter the expression of genes critical for muscle physiology, including energy metabolism, muscle regeneration, proteostasis, mitochondrial dynamics, and excitation–contraction coupling.

scholarly journals Iberian pig adaptation to acorn consumption: I. Net portal appearance of metabolites

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5861 ◽  
Author(s):  
Ignacio Fernández-Fígares ◽  
Jose Miguel Rodríguez-López ◽  
Lucrecia González-Valero ◽  
Manuel Lachica
Keyword(s):  
Sampling Period ◽  
Metabolic Energy ◽  
Blood Collection ◽  
Standard Diet ◽  
Deficient Diet ◽  
Protein Energy ◽  
Sampling Session ◽  
Protein Deficient Diet ◽  
Portal Plasma ◽  
Set Up

Most valuable cured products from Iberian pigs come from pure bred animals raised for a final grazing-fattening period where pigs eat mainly acorns, a low protein energy rich fruit. This is a nutritional challenge for animals fed equilibrated diets from weaning. The aim of the study was to determine net portal appearance (NPA) of metabolites in gilts fed acorns and evaluate adaptational changes after one week of feeding. Two sampling periods were carried out (after one day and after one week of acorn feeding) with six gilts (34 kg average BW) set up with three catheters: in carotid artery and portal vein for blood sampling, and ileal vein for para-aminohippuric acid (PAH) infusion to measure portal plasma flow (PPF). Pigs were fed at 2.5 × ME for maintenance a standard diet in two portions, at 09:00 (0.25) and 15:00 h (the remaining 0.75). On the day prior to the first sampling period, pigs were fed 2.4 kg of oak acorns. After feeding 0.25 of ration a 6 h serial blood collection was initiated. Following an identical protocol, a second sampling session was performed 1 week later. Adaptation to acorn consumption decreased NPA of ammonia (47%,P < 0.001). Although there was a transfer of urea from the gastrointestinal tract to the circulation in both sampling periods, no differences in NPA of urea was found (P > 0.05). NPA of glucose was not influenced by sampling period (P > 0.05), but NPA of lactate was greatly increased (231%,P < 0.001). There was a negative NPA of albumin although adaptation to acorn feeding did not alter it. Although NPA of triglycerides and cholesterol were unchanged, a subtle increase in arterial and portal cholesterol was noticed (9.6%,P < 0.01). Pigs fed a protein deficient diet for one week adapted decreasing NPA of ammonia for saving metabolic energy as less ammonia would become available for conversion to urea.

The ACL-deficient knee and the prevalence of meniscus and cartilage lesions: a systematic review and meta-analysis (CRD42017076897)

2019 ◽  
Vol 139 (6) ◽  
pp. 819-841 ◽  
Author(s):  
Julian Mehl ◽  
Alexander Otto ◽  
Joshua B. Baldino ◽  
Andrea Achtnich ◽  
Ralph Akoto ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Cartilage Lesions ◽  
Acl Deficient ◽  
Deficient Knee ◽  
And Cartilage

scholarly journals FGF2: a key regulator augmenting tendon-to-bone healing and cartilage repair

2020 ◽  
Vol 15 (9) ◽  
pp. 2129-2142
Author(s):  
Jun Zhang ◽  
Ziming Liu ◽  
Yuwan Li ◽  
Qi You ◽  
Jibin Yang ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Blood Vessels ◽  
Cartilage Repair ◽  
Bone Healing ◽  
Common Diseases ◽  
Cartilage Injuries ◽  
New Type ◽  
And Cartilage

Ligament/tendon and cartilage injuries are clinically common diseases that perplex most clinicians. Because of the lack of blood vessels and nerves, their self-repairing abilities are rather poor. Therefore, surgeries are necessary and also widely used to treat ligament/tendon or cartilage injuries. However, after surgery, there are still many problems that affect healing. In recent years, it has been found that exogenous FGF2 plays an important role in the repair of ligament/tendon and cartilage injuries and exerts a synergistic effect with endogenous FGF2. Therefore, FGF2 can be used as a new type of biomolecule to accelerate tendon-to-bone healing and cartilage repair after injury.

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