Local Disappearance of Epiphyseal Growth Plates in Rats with Hypervitaminosis A.

Kodaka, Tetsuo; Takaki, Hisashi; Soeta, Satoshi; Mori, Ryoichi; Naito, Yoshihisa

doi:10.1292/jvms.60.815

Cited by 18 publications

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“…In the present study, the highly calcified cartilage matrix, which was distinguished as granular high BSE signals [11] or the basophilic granules by HE staining [14], was detected within the epiphyseal growth plate in VA rats on Day 12. Such calcified cartilage matrix contained large calcospherulites in VA rats, but did not contain them in the hypertrophic zone in control rats.…”

Section: Discussionmentioning

confidence: 82%

“…The focal disappearance of the epiphyseal growth plate, i.e., premature closure of the epiphyseal growth plate, is regarded as the characteristic conformational feature in bovine Hyena disease and hypervitaminosis A [2-5, 18, 20]. In our previous study [11], we suggested that the high calcification of cartilage matrix in the epiphyseal growth plate was closely related to the focal disappearances of the epiphyseal growth plate, although the detailed process of the focal disappearance still remains unclear. In our recent study [17], we, therefore, experimentally administered a high dose of vitamin A to young rats to investigate the cellular and matrical alterations chronologically and demonstrated that initial disorders in the epiphyseal growth plate were attributed to the disturbance caused by a high dose of VA in the differentiation of chondrocytes.…”

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confidence: 99%

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Histological Disorders Related to the Focal Disappearance of the Epiphyseal Growth Plate in Rats Induced by High Dose of Vitamin A.

Soeta

Mori

Kodaka

et al. 2000

The Journal of Veterinary Medical Science

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ABSTRACT. The histological disorders related to the focal disappearance of the epiphyseal growth plate were examined histochemically in the proximal tibia of rats administered a high dose of vitamin A. Animals were given 100,000 IU/100 g body weight/day of vitamin A for 5 days from 4 weeks after birth (VA rats) or given deionized water as control and sacrificed on Day 12 and 19 of the experiment. Tibiae were examined by immunohistochemistry for type I, II and X collagens, lectin-histochemistry for Helix pomatia and backscattered electron imaging. On Day 12, the abnormally developed calcified cartilage matrix was detected within the epiphyseal growth plate in VA rats. The uncalcified cartilage matrix contained type I collagen but lacked type II collagen. In addition, the eroded regions accompanied with numerous osteoclasts and osteoblasts were detected in the epiphyseal growth plate. On day 19, eroded regions penetrated the epiphyseal growth plate to result in its focal disappearances with the eroded surfaces entirely covered with bone tissue in VA rats. These findings suggested that the cartilage matrix of the epiphyseal growth plate was abnormally calcified and showed the phenotypes like bone matrix. The eroded regions of the epiphyseal growth plate seemed to be caused by the invasion of osteoclasts into the altered cartilage matrix and might develop to the focal disappearances by the modeling or remodeling due to action of osteoclasts and osteoblasts. MATERIALS AND METHODS Animals and experiments:Wistar rats born in our laboratory were bred under conditions as described in our previous report [17]. Ten male rats aged 4 weeks, weighing 80-100 g, were given orally 100,000 IU/100 g body weight/ day of VA suspended in deionized water (VA rats) for 5 days. Similarly, another 10 male rats were given deionized water and used as control. Five VA rats as well as control rats were sacrificed on 7 days and 14 days after the end of the administration period (Day 12 and 19, respectively).Tissue preparation: The animals were perfused cardiacly with saline, followed by 4% paraformaldehyde in 0.1 M phosphate buffer at pH 7.4 under ether anesthesia. Proximal parts of tibiae were removed, cut into halves longitudinally and fixed in the same solution at 4°C overnight. A half of each tibia was decalcified in 10% EDTA in 0.01 M phosphate buffer at pH 7.4 at 4°C for 1 week. After dehydration through a graded series of ethanol at 4°C, decalcified tissues were embedded in paraffin and sectioned at 5 µm. The sections were stained by hematoxylin and eosin (HE) or processed for immunohistochemistry and lectin-histochemistry. The remaining half of each tibia was embedded without decalcification in methylmethacrylate and processed for backscattered electron (BSE) imaging.Immunohistochemistry: The imunohistochemistry for collagens was performed according to Mizoguchi et al. [12]. Rabbit antisera against rat type I collagen, bovine type II collagen and rat type X collagen were purchased from LSL (Tokyo, Japan). The procedure of the immunos...

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Section: Discussionmentioning

confidence: 82%

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confidence: 99%

Histological Disorders Related to the Focal Disappearance of the Epiphyseal Growth Plate in Rats Induced by High Dose of Vitamin A.

Soeta

Mori

Kodaka

et al. 2000

The Journal of Veterinary Medical Science

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“…In rats, vitamin A toxicity causes calcification of the epiphyseal-resting zone, with subsequent, complete disappearance of the growth plate [7,9]. In calves, vitamin A toxicity results in “hyena disease,” where premature epiphyseal closure of the hind limbs and the ensuing abnormal growth results in a gait disturbance resembling hyenas [3,8].…”

Section: Discussionmentioning

confidence: 99%

“…These defects manifest as an acquired chondrodysplasia in experimental animal models given high doses of vitamin A, with growth plate thinning, premature ossification of column cartilage and markedly reduced longitudinal bone growth even before premature growth plate closure [3,7-9], likely through wnt/catenin pathway activation or antagonizing Fibroblast Growth Factor Receptor (FGFR) signaling.…”

Section: Introductionmentioning

confidence: 99%

Premature Epiphyseal Closure of the Lower Extremities Contributing to Short Stature after <b><i>cis</i></b>-Retinoic Acid Therapy in Medulloblastoma: A Case Report

Noyes¹,

Levine

Belasco³

et al. 2015

Horm Res Paediatr

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Background: Prolonged cis-retinoic acid (RA) exposure contributes to premature epiphyseal closure. cis-RA is administered in various treatment regimens for pediatric cancers, thus increasing the risk for bone deformities and compromised growth. Results: We present a case of premature epiphyseal closure in a 9-year-old female with a history of medulloblastoma and treatment with a multimodal regimen including cis-RA. She was subsequently diagnosed with radiation-induced endocrine late effects including hypothyroidism and growth hormone deficiency (GHD). Seven months after initiation of GH therapy, an increased prominence of the wrists and knees combined with a deceleration in growth velocity prompted further evaluation; radiographs revealed bilateral premature closure of the distal femur and proximal tibia growth plates despite normal left wrist bone age. Conclusion: High doses of vitamin A and its analogs are linked to premature closure of the lower-extremity growth plates in animals and children. Pediatric brain tumor patients are at increased risk of growth failure due to concurrent radiation-induced GHD, damage to the spinal bones, and cis-RA-associated premature closure of the lower-extremity growth plates, with significant reduction in adult stature. A better appreciation of the detrimental effect of cis-RA on the growing skeleton is needed to monitor at-risk patients and to provide timely interventions.

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“…Outras pesquisas também descreveram uma diminuição do disco epifisário mediante um excesso de vitamina A (CLARK, 1970;CLARK;SEAWRIGHT, 1968;CLARK;GARTNER, 1970;DOIGE;SCHOONDERWOERD, 1988;KODAKA et al, 1998;SOETA et al, 1999). Soeta et al (1999) demonstrou que doses elevadas de vitamina A em ratos ocasiona uma disfunção dos condrócitos resultando na deformação e na diminuição da espessura do disco epifisário.…”

Section: Resultsunclassified

Efeitos da Hipervitaminose A sobre o Disco Epifisário de Fêmures de Ratos

et al. 2015

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RESUMO:A vitamina A (C20H30O) é um álcool (retinol) isoprenóide, insaturado, termoestável, lipossolúvel e insolúvel na água. Pode ser encontrado na forma precursora de β-caroteno, sendo transformada posteriormente nas suas formas ativas (ou pré-formadas) denominadas retinol, ácido retinóico e éster retilínicos. A vitamina A exerce diversas funções no desenvolvimento do ser humano, entretanto, o seu excesso causa várias manifestações, como sonolência, irritabilidade, dermatite escamativa, unhas frágeis, gengivite, fadiga, hipertensão, cefaléias intensas, fraqueza generalizada e fragilidade óssea. Sabendo que a vitamina A influencia no crescimento ósseo, o presente estudo propôs avaliar eventuais alterações produzidas no disco epifisário do fêmur de ratos em crescimento, submetidos a uma hipervitaminose A. Foram administradas, em ratos Wistar, doses na concentração de 150.000 UI (0,5 ml / 100g de peso) por via intraperitoneal e comparados com um grupo controle. Cada grupo composto por 8 animais foi sacrificado com 10, 20, 30 e 40 dias após a injeção e os fêmures foram removidos para obtenção de cortes histológicos. A morfometria dos discos epifisários demonstrou que os animais que receberam as doses elevadas de vitamina A apresentaram uma diminuição na espessura dos discos epifisários, condizente com uma maturação mais acelerada. Dessa forma, os resultados sugerem que excesso de vitamina A pode levar a um aumento no amadurecimento dos discos epifisários. PALAVRAS-CHAVE:Disco epifisário; Hipervitaminose A; Osteogênese. EFFECTS OF HYPERVITAMINOSIS ON THE EPIPHYSARY DISC IN RATS´ FEMURSABSTRACT: Vitamin A (C20H30O) is an isoprenoid, unsaturated, thermostable, lipid-soluble alcohol (retinol), insoluble in water which may be found in the precursory form of beta-carotene and later transformed in its active forms (or pre-formed) called retinol, retinoic acid and rectilinic ester. Although Vitamin A has several functions in human development, its excess causes several phenomena, such as sleepiness, irritability, squamous dermatitis, weak nails, gingivitis, fatigue, hypertension, intense headache, general weakness and bone fragility. Since Vitamin A affects bone growth, current analysis evaluates eventual changes in the epiphysary disc of growing rats´ femur when submitted to hypervitaminosis A. Doses at concentration 150.000 UI (0.5 ml / 100g weight) were administered in Wistar rats by intraperitoneal pathway and compared to control group. Each group composed of 8 animals was killed after 10, 20, 30 and 40 days after the injection, and femurs were removed for histological cuts. The morphometry of epiphysary discs showed that animals which received high doses of Vitamin A decreased the thickness of the epiphysary discs due to faster maturation. Results suggest that excess of Vitamin A may increase the maturity of the epiphysary discs.

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Local Disappearance of Epiphyseal Growth Plates in Rats with Hypervitaminosis A.

Cited by 18 publications

References 18 publications

Histological Disorders Related to the Focal Disappearance of the Epiphyseal Growth Plate in Rats Induced by High Dose of Vitamin A.

Histological Disorders Related to the Focal Disappearance of the Epiphyseal Growth Plate in Rats Induced by High Dose of Vitamin A.

Premature Epiphyseal Closure of the Lower Extremities Contributing to Short Stature after <b><i>cis</i></b>-Retinoic Acid Therapy in Medulloblastoma: A Case Report

Efeitos da Hipervitaminose A sobre o Disco Epifisário de Fêmures de Ratos

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