Vitamin D Metabolism Alteration in Acromegaly and Its Impact on Calcium-Phosphorus Metabolism

Abstract Objective: to evaluate metabolism of vitamin D and calcium-phosphorus metabolism in patients with an active phase of acromegaly in comparison with healthy individuals. Materials and Methods: The study included 44 patients with an active acromegaly (IGF-1 788 [521; 963] ng/mL), as well as 49 conditionally healthy individuals. There were more men in the Acromegaly group (41% vs. 20%, p <0.05), patients were older (median age 42.7 [35.5; 26.5] vs. 26.3 [25; 33.5] years, p <0.05) and had a higher BMI (28.4 [25.2; 30.2] vs. 22.2 [20.1; 26.1] kg/m2, p <0.05) in a minor way compared with the control group. All participants were tested for vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3) by UPLC-MS/MS, free 25(OH)D and vitamin D-binding protein by ELISA, PTH by electrochemiluminescence immunoassay, as well as routine biochemical parameters of blood serum (calcium, phosphorus, creatinine, albumin, magnesium) and urine (calcium and phosphorus-creatinine ratio in spot urine). Results: In the Acromegaly group, we observed significantly higher levels of serum total calcium (2.46 [2.37; 2.56] vs. 2.38 [2.33; 2.45] mmol/L, p <0.05), albumin-corrected calcium (2.33 [2.28; 2.42] vs. 2.26 [2.21; 2.31] mmol/L, p <0.05) and phosphorus (1.39 [1.25; 1.55] vs. 1.15 [1.06; 1.23] mmol/L, p <0.05) as well as lower levels of serum albumin (45 [44; 47] vs. 46 [45; 48] g/L, p <0.05). The rest of the studied biochemical parameters and PTH levels did not differ significantly between the groups. The IGF-1 level in patients with acromegaly positively correlated with the level of total calcium (r = 0.49, p <0.05), albumin-corrected calcium (r = 0.49, p <0.05) and phosphorus (r = 0.55, p <0.05). The Acromegaly group showed lower levels of 25(OH)D3 (14.8 [11.8; 20.5] vs. 20.5 [14.8; 24.6] ng/mL, p <0.05), 3-epi-25(OH)D3 (1.0 [0.7; 1.4] vs. 1.4 [0.9; 1.8] ng/mL, p <0.05), 24,25(OH)2D3 (0.8 [0.4; 1.2] vs. 1.7 [0.9; 2.6] ng/ml, p <0.05) and free 25(OH)D (4.6 [3.7; 5.6] vs. 5.9 [4.0; 7.5] pg/mL, p <0.05), higher levels of 1,25(OH)2D3 (50 [42; 63] vs. 39 [34; 45] pg/mL, p <0.05), a lower 25(OH)D3/1,25(OH)2D3 ratio (289 [226; 443] vs. 517 [340; 641], p <0.05) and a higher 25(OH)D3/24,25(OH)2D3 ratio (19.3 [15.4; 27.7] vs. 11.9 [9.6; 15.2], p <0.05). Conclusion: Our data suggest that high levels of the active vitamin D metabolite (1,25(OH)2D3) resulting from an increase in 1α-hydroxylase activity may contribute to the elevation of calcium and phosphorus serum levels in patients with acromegaly. Our results also indicate a decrease in 24-hydroxylase activity in patients with acromegaly, which may be due to lower levels of 25(OH)D3 in these patients. The results obtained should be evaluated taking into account the observed differences in age, gender and BMI between groups.

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MON-390 Vitamin D Metabolism in Patients with Acromegaly: A Case-Control Pilot Study

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1824 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Alexandra Povaliaeva ◽

Ekaterina Pigarova ◽

Artem Zhukov ◽

Larisa Dzeranova ◽

Victor Bogdanov ◽

...

Keyword(s):

Vitamin D ◽

Biochemical Parameters ◽

Reference Interval ◽

Control Group ◽

Vitamin D Metabolites ◽

Phosphorus Metabolism ◽

Creatinine Ratio ◽

Healthy Individuals ◽

Blood Calcium ◽

Calcium Phosphorus

Abstract Objective: to study the differences in the metabolism of vitamin D and calcium-phosphorus metabolism in patients with an active phase of acromegaly in comparison with healthy individuals. Materials and methods: The study included 8 patients with an active acromegaly, median age 36.5 ± 6.25 years, BMI 27.9 ± 1.95 kg/m2, IGF-1 907.3 ± 239 ng/ml, as well as 8 conditionally healthy individuals selected by age, sex and level of 25(OH)D determined by the immunochemiluminescent method (DEQAS certified). All participants were tested for calcium-phosphorus metabolism, PTH, and vitamin D metabolites by HPLC/MS-MS (25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3 and 24,25(OH)2D3) before oral administration of 150 000 IU of an aqueous solution of cholecalciferol and 7 days after administration. Results: In the Acromegaly group, on the 7th day after taking the drug, there was a statistically significant increase in 25(OH)D3 (89.8 ± 10.5 vs. 54.1 ± 14.8 nmol/L), 3-epi-25(OH)D3 (9.0 ± 2.6 vs. 3.3± 1.1 nmol/L) and 24,25(OH)2D3 (8.3 ± 1.9 vs. 6.4 ± 2.1 nmol/L), and a decrease of 25(OH)D2 (0.8 ± 0.2 vs. 1.1 ± 0.3 nmol/L) and a ratio of 24,25(OH)2D3 to 25(OH)D3 (0.1 ± 0.02 vs. 0.13 ± 0.03). A statistically significant increase in albumin-adjusted calcium was also noted (2.39 ± 0.14 vs. 2.31 ± 0.13 mmol/L). The medians of the levels of PTH and phosphorus initially were 27.1 ± 13.5 pg/ml and 1.6 ± 0.3 mmol/l and did not change by day 7 after taking the drug; creatinine and magnesium levels also remained the same. The level of calcium-creatinine ratio in a single portion of urine (CCR) was initially within the reference interval for all patients, its median did not change by day 7, however, in two patients there was a clinically insignificant increase higher than the upper limit of the reference interval; the phosphorus-creatinine ratio in a single portion of urine increased significantly. In the control group, after taking cholecalciferol similar changes in the levels of the studied vitamin D metabolites were observed, the levels of PTH also remained the same, however, there were no changes in the median biochemical parameters of blood and urine by day 7 after drug intake. Among the studied vitamin D metabolites, there were initially no significant differences between the groups; on day 7 a difference was recorded for the level of 3-epi-25(OH)D3 (9.0 ± 2.6 in the Acromegaly group vs. 18.8 ± 8.9 nmol/L in the control group). Among the biochemical parameters in the Acromegaly group higher levels of ionized blood calcium (1.14 ± 0.05 vs 1.1 ± 0.03 mmol/L), blood phosphorus (1.61 ± 0.26 vs 1.15 ± 0.09 mmol/L) and CCR were observed. Conclusion: Loading dose of cholecalciferol in patients with acromegaly is associated with less production of 3-epi-25(OH)D3, and results in lower inactive fraction of vitamin D than in healthy controls. More studies are needed to evaluate the effect of 1.25(OH)2D3 level on calcium-phosphorus metabolism in acromegaly.

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OR13-01 Comparison of Vitamin D Metabolism in Deficient and Sufficient States

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1869 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Artem Zhukov ◽

Alexandra Povaliaeva ◽

Ekaterina Pigarova ◽

Larisa Dzeranova ◽

Victor Bogdanov ◽

...

Keyword(s):

Vitamin D ◽

Biochemical Parameters ◽

Oral Intake ◽

Vitamin D Metabolites ◽

Loading Dose ◽

Healthy Individuals ◽

Vitamin D Metabolism ◽

Calcium Phosphorus ◽

Group A ◽

Group B

Abstract Objective: to study the differences in calcium-phosphorus and vitamin D metabolism in healthy individuals with deficient and sufficient baseline state of vitamin D. Materials and methods: The study included 16 young conditionally healthy individuals, divided into two equal groups: with levels of 25(OH)D below and above 30 ng/ml determined by the immunochemiluminescent method (Group A and Group B respectively; DEQAS certified). All participants were evaluated for the biochemical parameters of blood and urine, characterizing calcium-phosphorus metabolism, PTH by commercial methods, and vitamin D metabolites (25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3 and 24,25(OH)2D3) by HPLC/MS-MS before oral intake of 150 000 IU of an aqueous solution of cholecalciferol and 7 days after administration. Results: At baseline, the level of vitamin D metabolite 25(OH)D2 in Group B was lower with no significant differences in other studied parameters. In group A, strong positive correlations were observed between levels 25(OH)D3 and 3-epi-25(OH)D3, 24,25(OH)2D3, while in group B there were no such associations. After taking a loading dose of cholecalciferol, the groups showed generally similar changes in the studied vitamin D metabolites: a statistically significant increase in 25(OH)D3, 3-epi-25(OH)D3, a decrease in 25(OH)D2, and a ratio of 24,25(OH)2D3 to 25(OH)D3. However, the level of 24,25(OH)2D3 did not change in group B, with a significant increase in group A. The medians of the studied biochemical parameters in blood/urine, as well as PTH, remained unchanged in both groups. Conclusion: In patients with inadequate baseline levels of 25(OH)D, after a loading dose of cholecalciferol, there is a tendency to formation of more inactive forms of vitamin D. These deviations in the metabolism of vitamin D need to be clarified, since they can potentially affect the effectiveness of cholecalciferol therapy.

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CHARACTERISTICS OF EFFECTS PRODUCED BY OSTEOTROPIC DRUGS ON BONE REGENERATION OBTAINED FROM THE ANALYSIS OF CALCIUM-PHOSPHORUS METABOLISM IN THE EXPERIMENT AND CLINICAL FINDINGS OF RADIOLOGICAL EXAMINATIONS

Актуальні проблеми сучасної медицини Вісник Української медичної стоматологічної академії ◽

10.31718/2077-1096.20.4.124 ◽

2020 ◽

Vol 20 (4) ◽

pp. 124-129

Author(s):

I.V. Han ◽

A.I. Furdychko ◽

M.P. Ilchyshyn ◽

I.R. Fedun ◽

N.V. Porokhovska

Keyword(s):

Comparison Group ◽

Root Apex ◽

Calcium Hydroxyapatite ◽

Control Group ◽

Tooth Root ◽

Phosphorus Metabolism ◽

Periodontal Tissues ◽

Calcium Phosphorus ◽

Calcium And Phosphorus ◽

Experimental Group

The treatment of patients with chronic periodontitis is one of the important and is still not completely solved problems of modern dentistry due to its high prevalence and the number of complications, which may follow the treatment. Long-term asymptomatic course of chronic forms of periodontitis promotes the progression of destructive processes not only in periodontal tissues and alveolar bone, but also stimulates the resorption of cementum and the root dentin, which causes the formation of the acquired wide dental root apex. This prompted the search for new and more effective methods of the treatment. The aim of our study was to evaluate the effectiveness of the effect produced by calcium hydroxyapatite-based composition based on the intensity of regenerative processes in bone tissue in the experiment, analyzing the results of calcium-phosphorus metabolism, and to study the effectiveness of the treatment of patients with chronic granulating periodontitis with an acquired wide tooth root apex using the developed composition, and then to compare with the results of using the generally applied mineral trioxide aggregate (MTA) material. All animals were divided into 4 experimental groups, and the modelled destruction of their bone tissues was filled with the studied material, except for the comparison group. The test animals were killed on 14th and 90th days of the experiment. The content of calcium and phosphorus in the bone tissue homogenate was investigated. Then we divided 59 patients into two groups: the experimental group, in which the apical part of the tooth root was filled with the proposed calcium hydroxyapatite-based composition for revitalization and bioreparation of periapical tissues, and the comparison group, in which the jaw bone defects were filled with the MTA material. On the 14th day, the largest (1.8-fold) decrease in calcium and phosphorus ions was observed in the 2nd experimental group, while in the 4th group it was 1.3 time lower. On the 90th day, the content of calcium and phosphorus ions was still lower than in the control group in 1.6 and 1.5 times, respectively, and in 4th group in 1.01 and 1.1 time. Analysis of the treatment results of patients in 6 month therapy has demonstrated a decrease in the value of the SDVP index in the experimental group in 1.4 times, and in the control group in 1.1 time. In 12 months the experimental group demonstrated the 1.9-fold index decrease, while the comparison group had only 1.4-fold lowering of this value. We have demonstrated experimentally, clinically and radiologically that the proposed composition is more effective in promoting the processes of biorevitalization and regeneration of periodontal tissues compared to the generally applied MTA material.

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Disorders of calcium and phosphorus metabolism in patients with acquired heart diseases

Patologiya krovoobrashcheniya i kardiokhirurgiya ◽

10.21688/1681-3472-2013-3-8-12 ◽

2015 ◽

Vol 17 (2) ◽

pp. 8

Author(s):

I. Yu. Zhuravleva ◽

A. V. Veremeev ◽

O. N. Khryachkova ◽

N. G. Nikonorova

Keyword(s):

Vitamin D ◽

Alkaline Phosphatase ◽

Superoxide Dismutase ◽

Heart Disease ◽

Parathyroid Hormone ◽

Heart Diseases ◽

Phosphorus Metabolism ◽

Calcium Phosphorus ◽

Calcium And Phosphorus ◽

Rheumatic Heart

Some calcium/phosphorus metabolism indices were studied in patients with rheumatic heart disease (RHD) and patients with infective endocarditis (IE). Concentrations of calcium, phosphorus, parathyroid hormone (PTH), vitamin D, superoxide dismutase (SOD), the total amount of peroxides and the activity of alkaline phosphatase and its bone isoenzyme were measured in the blood serum of 88 patients (men aged 65 years, with 67 of them having RHD and 21 -IE). Hypocalcemia, vitamin D deficiency, an increase in PTH and peroxides, as well as a significant decrease in SOD concentrations when compared to the reference values were detected in both groups. The patients with IE had increased osteocalcin concentrations and higher alkaline phosphatase activity, while those with RHD were diagnosed with hypophosphatemia. Some mechanisms and pathogenic relationships of the identified abnormalities are discussed. RHD and IE are shown to lead to significant disorders of systemic calcium/phosphorus metabolism.

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Bone metabolism biomarkers in walking children with cerebral palsy

Pediatric Traumatology Orthopaedics and Reconstructive Surgery ◽

10.17816/ptors7479-86 ◽

2020 ◽

Vol 7 (4) ◽

pp. 79-86

Author(s):

Vladimir M. Kenis ◽

Svetlana L. Bogdanova ◽

Tatyana N. Prokopenko ◽

Andrei V. Sapogovskiy ◽

Tatyana I. Kiseleva

Keyword(s):

Vitamin D ◽

Alkaline Phosphatase ◽

Cerebral Palsy ◽

Bone Metabolism ◽

Control Group ◽

Study Group ◽

Flat Feet ◽

Children With Cerebral Palsy ◽

Calcium Phosphorus ◽

Orthopedic Patients

Backgrоund. Osteoporosis is an important factor in the pathogenesis of orthopedic manifestations in children with cerebral palsy. It was previously demonstrated that children with cerebral palsy have specific changes in bone metabolism, which can cause changes in laboratory parameters compared with other orthopedic patients without neurological backgrounds. Aim. The aim of this study was to assess bone metabolism biomarkers in children with cerebral palsy, identifying distinguishing characteristic patterns in comparison with patients with orthopedic pathology without neurological backgrounds. Materials and methods. This study evaluated the concentrations of calcium, phosphorus, -cross laps, osteocalcin, vitamin D, CICP, and alkaline phosphatase in the blood serum of 50 children with cerebral palsy aged between 6 to 12 years with GMFCS levels IIII. The control group consisted of 50 patients with plano-valgus deformities of the feet. Results. The alkaline phosphatase activity in the group of children with cerebral palsy was 170.25 59.35 u/L, while in the control group it was 145.58 46.29 u/L; the CICP concentration in the study group was higher than in the control group (324.01 174.10 and 269.68 240.98, respectively). The concentration of -cross laps, osteocalcin, calcium, and vitamin D in the study group was lower than in children with flat feet. Conclusions. This study demonstrated multidirectional changes in the biomarkers of bone metabolism that are characteristic of walking children with cerebral palsy. These changes are characterized by a corresponding increase in the activity of osteoresorption and osteoreparation. This makes it possible to justify the combined use of metabolites and metabolic activators (calcium and vitamin D) and drugs that suppress osteoresorption (bisphosphonates) for the prevention and treatment of osteoporosis in children with cerebral palsy.

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Assessment of Vitamin D Metabolism in Patients with Cushing’s Disease in Response to 150,000 IU Cholecalciferol Treatment

Nutrients ◽

10.3390/nu13124329 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4329

Author(s):

Alexandra Povaliaeva ◽

Viktor Bogdanov ◽

Ekaterina Pigarova ◽

Artem Zhukov ◽

Larisa Dzeranova ◽

...

Keyword(s):

Vitamin D ◽

Cushing’S Disease ◽

Serum Vitamin ◽

Urinary Free Cortisol ◽

Cushing's Disease ◽

Control Group ◽

Vitamin D Metabolites ◽

Vitamin D Metabolism ◽

Serum Vitamin D ◽

Free Cortisol

In this study we aimed to assess vitamin D metabolism in patients with Cushing’s disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D3 levels (p > 0.05) and higher 25(OH)D3/24,25(OH)2D3 ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D3/24,25(OH)2D3 ratio (r = 0.36, p < 0.05). The increase in 25(OH)D3 after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently lower 25(OH)D3/24,25(OH)2D3 ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.

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ROLE OF VITAMIN D IN ETIOPATHOGENESIS AND METABOLIC ABNORMALITIES SEEN IN POLYCYSTIC OVARIAN SYNDROME

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i9.33310 ◽

2019 ◽

pp. 215-219

Author(s):

SURANKITA SUKUL ◽

JYOTIRMAYEE BAHINIPATI ◽

ASHOK KUMAR DAS

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Negative Correlation ◽

Biochemical Parameters ◽

Polycystic Ovarian Syndrome ◽

Serum Insulin ◽

Control Group ◽

Insulin Metabolism ◽

Ovarian Syndrome

Objective: Polycystic ovarian syndrome (PCOS) is a common cause of ovarian dysfunction in women in reproductive age group. It is now the leading cause of infertility among premenopausal women. PCOS women usually suffer from metabolic disturbances and insulin resistance (IR). Vitamin D has shown a significant role in glucose and insulin metabolism. Correlation studies have been done to examine the role of vitamin D in PCOS. However, still, Vitamin D status in PCOS remains varied. This study is an attempt to find out the association of Vitamin D with etiopathogenesis and metabolic risk factors seen in PCOS. Methods: Hundred subjects (50 PCOS and 50 age-matched normal control) were recruited for the study. Difference in biochemical parameters in PCOS women and normal group was measured, and association of Vitamin D with etiological and biochemical parameters in PCOS was seen. Results: There was a significant (p<0.001) increase in body mass index, serum insulin, fasting blood sugar (FBS), serum cholesterol, triglyceride, and low-density lipoprotein in PCOS. IR was observed in PCOS cases (homeostatic model assessment for β-cell function and IR = 6.40±1.96) compared to the control group (2.43±0.53). Serum 25(OH) Vitamin D3 was significantly decreased in PCOS (9.04±2.60 ng/ml) compared to control group (20.06±3.28 ng/ml). Negative correlation of serum Vitamin D was found with FBS, serum insulin, IR, HI, and serum testosterone. Vitamin D with metabolic parameters also showed a statistically significant negative correlation. Conclusion: Vitamin D deficiency may be a common comorbid manifestation of PCOS. Hence, Vitamin D supplementation may decrease the potential risk of morbidity and mortality associated with PCOS. However, further studies are needed which should include assessment of Vitamin D in women at various stages of PCOS to enhance the temporal order of Vitamin D deficiency in relation to PCOS.

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Effect of Vitamin D Supplementation on Doxorubicin-Induced Cardiotoxicity in Rats

QJM ◽

10.1093/qjmed/hcaa065.004 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

F M A Diab ◽

N A Nassef ◽

M S Abdelhamid ◽

Y M K Amin

Keyword(s):

Vitamin D ◽

Cardiac Dysfunction ◽

Cardiac Tissue ◽

Isolated Heart ◽

Muscle Fibers ◽

Vitamin D Supplementation ◽

Control Group ◽

Total Calcium ◽

Significant Prolongation

Abstract Background Doxorubicin-induced cardiotoxicity is a worldwide problem. Vitamin D is a well-known beneficial vitamin for bone growth and calcium homeostasis but recently it is also known for its cardioprotective effects. The aim of this study is to investigate the potential protective role of vitamin D on the cardiac dysfunction induced by chronic doxorubicin exposure, and to throw more light on the possible underlying mechanism (s) for such effect. Materials and Methods: 70 female Albino-rats were divided into 4 groups; control group (C), Doxorubicin-treated group (Dox): given i.p. injection of Dox in a dose of 2.5 mg/kg body weight (cumulative dose: 15 mg/kg) over 3 weeks, vitamin Dsupplemented group (Vit D): given vitamin D by oral gavage in a dose of 500 IU/kg daily, 5 days a week, also for 3 weeks and the combined Doxorubicintreated+vitamin D-supplemented group (Dox+Vit D). At the end of the experiment, ECG was recorded and in vitro isolated heart study was performed on Langendoroff preparation to measure peak tension (PT), time to peak tension (TPT), half relaxation time (HRT) and myocardial flow rate (MFR). Body and cardiac weights, plasma levels of brain naturetic peptide (BNP), cardiac troponin I (cTnI), vitamin D and total calcium and cardiac tissue heat shock protein 20, total antioxidant capacity (TAC) and malondialdehyde (MDA) were measured. Also, cardiac tissues were histopathologically assessed. Results: Dox-treated rats showed significant decrease in the final body weight (fBW), significant prolongation of the P-R interval, QRS duration, observed Q-T (Q-TO) and corrected Q-T (Q-Tc) with significant depression of the R voltage. In addition, there was a significant decrease in the in vitro heart rate, significant depression in PT, PT/LV and MFR together with significant prolongation in TPT& 3 HRT. These changes were accompanied by significant elevation of plasma BNP, cTnI and in cardiac tissue MDA and a significant decrease in plasma vit D, total calcium and cardiac tissue TAC and HSP20. Histopathological examination revealed markedly distorted muscle fibers with indistinct cell borders, bright eosinophilic cytoplasm, intra-cytoplasmic vacuoles and small pyknotic nuclei or absent nuclei, together with interstitial edema & aggregates of inflammatory cells and thick irregular collagen fibers in between the muscle fibers. Concomitant supplementation of vitamin D to the doxorubicin treated rats resulted in significant decrease in PR interval, QRS duration, MDA and significant increase PT, PT/LV, MFR, MFR/LV, plasma vitamin D, total calcium and TAC compared to the Dox treated rats to be insignificantly different from the control group. Plasma BNP and cTnI were significantly decreased while cardiac HSP20 was significantly increased compared to the Dox-treated rats, yet these parameters were still significant from the control group. Meanwhile, fBW, Q-TO and Q-Tc intervals, and TPT remained insignificantly changed from the DOX group. These findings were associated by regaining the normal collagen fiber distribution between cardiac muscle fibers with resolution of interstitial edema. Conclusion: Vitamin D supplementation can partially mitigate cardiac dysfunction induced by chronic doxorubicin by improving the cardiac antioxidant state and heat shock protein 20 level. Key words: Doxorubicin, cardiac dysfunction, vitamin D, isolated heart studies, BNP, HSP20.

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