Exposure to endocrine disruptors and alterations in mineralized tissues: a narrative review / Exposición a disruptores endocrinos y alteraciones en tejidos mineralizados: revisión narrativa

Background: Endocrine Disrupting Chemicals (EDCs) would cause alterations in organs/systems of exposed individuals or their progeny. Objetive: To identify and analyze the main published findings on the effects of exposure to EDCs on teeth, cartilage, and bone. Material and Methods: Two databases were analyzed: Medline and Web of Science. Only observational studies analyzing the effect of EDCs on mineralized tissues published since 2006 were included in the study. Results: 25 articles were selected, most of them involving EDCs pesticides, plasticizers, or personal care products, highlighting organochlorine compounds, bisphenols, phthalates, dioxins, parabens, and perfluoroalkyls. Thirty-six per cent of the studies reported an accumulation of EDCs in teeth or bones, while 64% reported alterations in their development or morphology, mainly at the bone level, primarily affecting their mineral density and size, as well as that of the bones of exposed individuals or their progeny. The type of effect observed was related to the EDCs analyzed, and it seemed to depend on variables such as age, sex, ethnicity/race, and even the metabolic status of the individuals in the different species analyzed. No evidence associated with effects on cartilage was found. Conclusion: EDCs in the environment, at work, or at home, under different exposure routes, are capable of accumulating in teeth and bone, particularly affecting the latter. It is necessary to study the effect of EDCs on mineralized tissues in agro-industrial areas, especially on teeth.

Antecedentes: Los Químicos Disruptores Endocrinos (EDCs) causarían alteraciones en órganos/sistemas de individuos expuestos, o su progenie. Objetivo: Identificar y analizar los principales hallazgos publicados sobre el efecto de la exposición a EDCs en dientes, cartílago y hueso. Material y Métodos: Se analizaron dos bases de datos: Medline y Web of Science, incluyendo solo estudios observacionales publicados desde el 2006, analizando el efecto de los EDCs sobre tejidos mineralizados. Resultados:25 artículos fueron seleccionados, siendo la mayoría de los EDCs pesticidas, plastificantes o productos de cuidado personal, destacando los compuestos Organo-clorados, Bisfenoles, Ftalatos, Dioxinas, Parabenos y los Perfluoroalquilos. Un 36% de los estudios reportaron un acúmulo de EDCs en dientes o huesos, mientras que un 64% informaron de alteraciones en su desarrollo o morfología, particularmente a nivel de huesos, afectando principalmente su densidad mineral y su tamaño, así como el de los individuos expuestos o su progenie. El tipo de efecto observado tuvo relación con el EDCs analizado, pareciendo depender de variables tales como edad, sexo, etnia/raza e incluso el estado metabólico de los individuos, en las diferentes especies analizadas. No se encontraron evidencias asociadas a efectos en el cartílago. Conclusión: Los EDCs en el medio ambiente, ámbito laboral o doméstico, bajo distintas rutas de exposición, son capaces de acumularse en diente y hueso, afectando particularmente a este último. Es necesario estudiar el efecto de los EDCs en los tejidos mineralizados en zonas agroindustriales, particularmente a nivel de dientes.

[ harmful effect of quinolone [pefloxacine] on immature cartilage in juvenile rat]

The aim of our study was definition of the exact mechanism by which quinolone harm the immature cartilage causing arthropathy, and upon these results we can determine the suitable treatment for this damage. This effect was studied in four groups of juvenile wistar rats as following:1- normal group.2- the group of pefloxacine with a dose 15 mg/kg per day for one month. 3- the group of pefloxacine 15mg/kg per day for one month with addition of the magnesium ions with compensate amount 84mg/kg per art. 4- the group of pefloxacine 15mg/kg per day for one month with addition of vitamin E with compensate amount75mg/kg per rat. The drugs were administered by incubation tube for one months, and at the end of the experiment blood samples were took from animals hearts preparing for measuring malondialdehide, then animals were scarified and the maximum extension angle of the knee joints was measured, then we put the joints in the formol for the histological study. Pefloxacine increased the values of maximum extension angle significantly in compare to the normal group and the control group, with significant improvement in the group of magnesium ions and the group of vitamin E but non of each group could return the cartilage to the normal condition. The results of malondiadehyde assay inssure the effect of free radicals in this arthropathy. Histological study: pefloxacine damage significantly the cartilage and the damage was decreased in the addition of magnesium or vitamin E. There is a lot of factors participate in causing the arthropathy which induced by taking quinolone and this pathology don't confine on the participate of magnesium ions or oxidative stress.

[Investigation of the preventive effect of glucosamine, chondroitin alone and in combination on cartilage insult caused by quinolone in juvenile rats]

Osteoarthritis is considered the most common joint disease in the world, especially among the aged population. But it may affect the kids as a secondary type when kids were administered some groups of drugs such as quinolones which cause cartilage deformations and predispose to secondary type of osteoarthritis. This study aims to investigate the protective effect of glucosamine and chondroitin alone and in combination in the treatment of arthritis in Juvenile Rats. This study was applied on 5 groups of juvenile wistar rats, which divided as: normal group, control group, the group of GA, group of CS, the group of combination between GA+CS. At the end of the study all of rats were killed, then measurement of maximum extension of the right knee were performed, also histological and functional analysis of the articular cartilage of the knee were performed. Control group showed the degenerative changes as compared to the normal group, which is improved into the groups of GA, CS, which distinguished from the combination group. This study shows that GA and CS have protective effect able to opposite the destructive effect of quinolone on immature cartilages

Effects of Risedronate on Osteoarthritis of the Knee

The purpose of the present study was to discuss the effects of risedronate on osteoarthritis (OA) of the knee by reviewing the existing literature. The literature was searched with PubMed, with respect to prospective, double-blind, randomized placebo-controlled trials (RCTs), using the following search terms: risedronate, knee, and osteoarthritis. Two RCTs met the criteria. A RCT (n = 231) showed that risedronate treatment (15 mg/day) for 1 year improved symptoms. A larger RCT (n = 1,896) showed that risedronate treatment (5 mg/day, 15 mg/day, 35 mg/week, and 50 mg/week) for 2 years did not improve signs or symptoms, nor did it alter radiological progression. However, a subanalysis study (n = 477) revealed that patients with marked cartilage loss preserved the structural integrity of subchondral bone by risedronate treatment (15 mg/day and 50 mg/week). Another subanalysis study (n = 1,885) revealed that C-terminal crosslinking telopeptide of type II collagen (CTX-II) decreased with risedronate treatment in a dose-dependent manner, and levels reached after 6 months were associated with radiological progression at 2 years. The results of these RCTs show that risedronate reduces the marker of cartilage degradation (CTX-II), which could contribute to attenuation of radiological progression of OA by preserving the structural integrity of subchondral bone. The review of the literature suggests that higher doses of risedronate (15 mg/day) strongly reduces the marker of cartilage degradation (CTX-II), which could contribute to attenuation of radiological progression of OA by preserving the structural integrity of subchondral bone.

The Protective Effect of Sodium Hyaluronate on the Cartilage of Rabbit Osteoarthritis by Inhibiting Peroxisome Proliferator-Activated Receptor-Gamma Messenger RNA Expression

PURPOSE: The purpose of this study was to study the protective effect and influence of sodium hyaluronate (Na-HA) on mRNA expression of peroxisome proliferators-activated receptor gamma (PPAR-gamma) in cartilage of rabbit osteoarthritis (OA) model. MATERIALS AND METHODS: Forty eight white rabbits were randomly divided into A, B, and C groups. Group A was normal control group, B and C groups underwent unilateral anterior cruciate ligament transection (ACLT). The rabbits in group B were injected normal saline after ACLT; and Group C received intraarticular1% sodium hyaluronate (HA) injection 5 weeks after surgery, 0.3 mL once a week. At 11th week after surgery, all the rabbits were sacrificed. The cartilage changes on the medial femoral condyles were graded separately. Cartilage sections were stained with safranin-O and HE, and messenger RNA (mRNA) expression of PPAR-gamma was detected by using real time polymerase chain reaction (Real Time-PCR). RESULTS: Cartilage degeneration in group B was significantly more severe than in A and C injection group. The grey value of Safranin-O of B group was higher than A and C groups. Expression of PPAR-gamma mRNA in group B was higher than group A and C. CONCLUSION: This study shows that Na-HA has a protective effect on articular cartilage degeneration, and the inhibitory effect on the PPAR-gamma mRNA expression may be one of therapeutic mechanism of Na-HA.

Preventive role of zinc chloride against toxicity of ciprofloxacin on the growing cartilage of wistar albino rat litter

To assess the preventive role of zinc chloride on toxicity of ciprofloxacin administration in wistar albino rat litter. It was a Prospective experimental study. The study was carried out in the department of Anatomy, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi, Pakistan during March 2002 to February 2003 one year study. Ciprofloxacin and zinc chloride were administered to newly born albino rat litters separately and simultaneously at a dose of 20 mg/kg body weight and 1200 micro g/Kg body weight respectively, intraperitonealy twice daily from 1-14 day after birth. The animals were sacrificed by deep ether anaesthesia. The fore and hind limbs were dis-articulated from the axial skeleton, soft tissue was removed and bones were fixed in 10% buffered formalin. Decalcification was done in 10% nitric acid and 10% formic acid changes. After paraplast embedding, 4 micro m thick longitudinal sections of proximal and distal ends of long bones were cut by a rotary microtome. Routine staining with haemotoxylin and eosin was performed. Histomorphometery was done to measure the thickness of epiphyseal cartilage and was compared with similar values of the control animals. The results were statistically analyzed to evaluate the significance. Our study revealed that ciprofloxacin administration in new born albino rat litter decreased the width of epiphyseal growth plate cartilage by 13.7 +/- 0.42 micro m, 10.43% in humerus and 6.6 +/- 1.2 micro m 4.72% in femur as compared to control, whereas, simultaneous zinc chloride administration restricted the decrease to 1.27 micro m +/- SD in humerus and 2.05 micro m +/- SD in femur. Simultanous zinc chloride administration minimized the epiphseal cartilage damage induced by ciprofloxacin in Wistar albino rat litter

Effects of glucosamine on the tibial epiphyseal disk of ovariectomized rats: morphologic and morphometric analysis

OBJECTIVE: The aim of this study was to analyze the effect of glucosamine sulfate on the tibial epiphyseal disk of the ovariectomized rats. METHODS: After ovariectomy (OVx), 28 female rats were randomly divided into 4 experimental groups with 7 animals each, treated as follows: OVx 21 - vehicle (NaCl 0.9 percent) 0.5 mL/day) for 21 days; OVx GS21 - 230 mg/kg/day glucosamine sulphate for 21 days; OVx 45 - treated with NaCl 0.9 percent as above for 45 days; and OVx - GS45230 mg/kg/day glucosamine sulphate for 45 days. Seven intact animals in the proestrous phase were used as controls (CG). Upon treatment completion, the animals were sacrificed and the left knee joint was dissected and prepared for histological analysis. RESULTS: The percentage of remaining cartilage in new bone of the CG; that found in THE OVx GS45 group was significantly less than that of the OVx 21, OVx GS21, and OVx 45 groups. The percentage of trabecular bone in proestrous animals was the highest. The OVx GS45 group showed higher values compared with the other ovariectomized groups. These results were paralleled by the findings regarding the cells of the proliferative zone, since the CG had the highest values, and the values of the OVx GS45 group were greater than those of the OVx 21, OVx GS21, and OVx 45 groups. CONCLUSION: Our studies suggested that glucosamine may stimulate tibial cartilage and bone growth after ovariectomy in rats.

OBJETIVO: O alvo deste estudo foi analisar o efeito do sulfato de glicosamina no disco epifisário da tíbia em ratas ooforectomizadas. MÉTODOS: Após a ooforectomia (OVx), 28 ratas foram aleatoriamente divididas em 4 grupos experimentais de 7 animais cada, tratados da seguinte maneira: OVx 21 - veículo (0,5ml de NaCl 0.9 por cento ip uma vez ao dia) por 21 dias; OVx GS21 230 - mg/kg peso corporal por dia de sulfato de glicosamina, 21 dias; OVx 45 - tratados com NaCl 0.9 por cento igual ao grupo OVx 21, por 45 dias; e OVx GS45 - 230 mg/kg peso corporal por dia com sulfato de glicosamina, 45 dias. Sete animais intactos, na fase de proestro, foram usados como controle (CG). Ao completar o tratamento, os animais foram sacrificados e a articulação do joelho esquerdo foi dissecada e preparada para análise histológica. RESULTADOS: A porcentagem de cartilagem remanescente no novo osso do CG foi a menor. Os achados no grupo OVx GS45 foi significantemente menor do que no grupo OVx 21, OVx GS21 e OVx 45. A porcentagem de osso trabecular nos animais em pró-estro foi a maior. O grupo OVx GS45 mostrou valores maiores em relação aos outros grupos ooforectomizados. Esses resultados foram correspondentes aos achados em relação às células da zona proliferativa, desde que o CG teve os maiores valores e os valores do grupo OVx GS45 foram superiores aos dos grupos OVx 21, OVx GS21 e OVx 45. CONCLUSÃO: Nossos estudos sugerem que a glicosamina pode estimular o crescimento da cartilagem e do osso tibial após a ooforectomia em ratas.

Effect of Ciprofloxacin on growing cartilage in albino Rat pups

Administration of quinolone therapy is controversial during growing age as stated by earlier worker. The flroquinolones are currently not indicated for young children, because of arthropathy and adverse effect on growing cartilage shown by studies. However the effects of ciprofloxacin on epiphyseal growth plate has remained undocumented. This study is therefore, undertaken to determine the risk of ciprofloxacin administration an growing cartilage by prospective experimental animal study model using Wistar albino rat pups. Ciprofloxacin was administered to newly born Wistar albino rat pups with a doze of 20mg/kg body weight intraperitonealy twice a day from day-1 to day-14 after birth. The animals were sacrificed by deep ether anesthesia. The limbs were disarticulated from axial skeleton, soft tissue was removed. The intact bone mean length in millimeter of right and left humerus and femur was measured with the help of electronic vernier caliper and bones were fixed in 10% buffered farmalin. Decalcification was done in 10% nitric acid and 10% formic acid changes. After paraplast embeding, 4 mm thick longitudinal sections of the proximal long bones were cut by a rotary microtome. Routine staining with haemotoxylin and eosin was performed. Histomorphometry was done measuring the thickness of epiphyseal cartilage and was compared with similar value of control animals. The results were statistically analysed to find out the significance. The ciprofloxacin induces a mordanting effect as abviated by increased basophilia. Our study reveales that cirprofloxacin administration in the newly born pups decreased the width of epiphyseal growth plate cartilage by 10.43% in humerus and 4.72% in femur as compared to the growth of control cartilage. The decrease in the width was brought about mainly by the reduced count of the proliferative cells in the proliferative zone and the diminuation in the average size of the hypertrophic condryocytes in the hypertrophic zone. The reserve zone has become markedly reduced in thickness. The ciprofloxacin post-natal administration effected growth plate retardation by inhibiting the mitosis in the proliferative zone and also effected the mean length of humora and femora leading to reduction in limb length of rat pups

Safety profile of ciprofloxacin used for neonatal septicemia.

We conducted a case matched control study to observe the adverse effects of ciprofloxacin used in neonatal septicemia We enrolled 30 neonates with multidrug-resistant septicemia who were treated with intravenous ciprofloxacin for 14 days. Thirty matched neonates with septicemia treated with other antibiotics were enrolled as controls There was no difference in the mean serum electrolytes, hepatic, renal and hematologic parameters of the two groups. Serial ultrasonographic measurements of the cartilage of the knee after 1 and 6 months showed no difference in the two groups. The femoral cartilage showed an increase of 78.8% in the mean longitudinal area after 6 months in the study group. In the control group, the femoral cartilage showed a 78.4% increase after 6 months. Similarly, the tibial cartilage showed no difference in the percentage increase in size of the study and control group at the end of 6 months. When controlled for birth weight and gestation, cartilage size was not affected by ciprofloxacin.

Alteraciones en la matriz organica del hueso y cartilago de rata por el uso prolongado de fluoruno de sodio / Alterations in the organic matrix of bone and cartilage after prolonged administration of sodium fluoride in the rat

Los fluoruros, por mecanismos aun no aclarados, estimulan la formación ósea y son, en consecuencia, usados en el tratamiento de las osteoporosis. Desde un punto de vista terapéutico, uno de los efectos más esperados por la ingesta de fluoruro en pacientes osteoporóticos es la disminución en el índice de fracturas. Si bien esto ocurre, observaciones clínicas sugieren que este efecto es menor que el esperado por el aumento de la masa ósea (ej.: la resistencia por unidad de tejido estaría disminuida en el hueso fluorótico). El o los mecanismos por los cuales el fluoruro conduce a las alteraciones mencionadas, todavía no son bien conocidos, pero como el componente inorgánico ha sido extensamente estudiado, hemos llevado a cabo este trabajo con el objeto de caracterizar cuali y cuantitativamente a los GAG y el colágeno de hueso y cartílafo de rata, en función de la ingesta prolongada de fluoruro de sodio. Las variaciones producidas por la ingesta de fluoruro implican un aumento significativo en la concentracicón de GAG, después de dos meses de tratamiento, debidas a un incremento en las fracciones correspondentes al condroitín-6-sulfato y dermatán sulfato. Esta modificación en el patrón de distribución de los GAG no es atribuible a variaciones en el peso de las moléculas. Aunque otros estudios han informado que no se observan efectos sobre la síntesis de colágeno o de DNA, como consecuencia de la ingesta de fluoruro, nuestros resultados muestran que el contenido de OH-Pro se halla aumentado significativamente luego de 2 meses de tratamiento. Los datos presentados sugieren que las alteraciones óseas inducidas por el fluoruro, podrían se, al menos en parte, debidas a cambios en la concentración y distribución de los GAG y el colágeno en la matriz calcificable de hueso y cartílago de rata