الفهرس 
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Abstract
The present study was planned 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.
The study was performed on 70 female albino rats which were divided into 4 groups:
group 1: Control group (Control) (n=21):
Rats in this group received six doses of intraperitoneal (i.p) saline injections twice weekly for 3 weeks and 0.1 ml distilled water by gavage 5 days a week, for 3 weeks.
group 2: Doxorubicin-treated group (Dox) (n=18):
Rats in this group received six doses of intraperitoneal injection (i.p) of doxorubicin in a dose of 2.5 mg/kg body weight twice weekly for 3 weeks (cumulative dose: 15 mg/kg) (Akolkar et al., 2017) and 0.1 ml distilled water by gavage 5 days a week for 3 weeks.
group 3: Vitamin D-supplemented group (Vit D) (n=16):
Rats in this group received vitamin D via oral gavage (500 IU/kg body weight daily 5 days a week) (Chabas et al., 2013) for 3 weeks and six doses of i.p saline injection twice weekly for 3 weeks.
Group4: Vitamin D-supplemented, doxorubicin-treated group (VitD+Dox) (n=15):
Rats in this group received concomitant doses of vitamin D and doxorubicin. Vitamin D was given in a dose as group 3 together with doxorubicin using the same dose as in group 2.
At the end of the experiment, ECG was recorded and in vitro isolated heart study was performed on Langendorff 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 (HSP20), total antioxidant capacity (TAC) and malondialdehyde (MDA) were evaluated. Also, cardiac tissues were histopathologically assessed.
The results obtained from the present study revealed that Dox-treated rats showed significant decrease in the final body weight (fBW), significant prolongation of the PR interval, QRS duration, observed Q-T (Q-TO) and corrected Q-T (Q-Tc) with significant depression of the R wave 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, HRT and CT. 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 being 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, TPT and CT remained insignificantly changed from the Dox group.
These findings were associated by regaining the normal collagen fiber distribution between cardiac muscle fibers, mild interstitial edema with no vacuoles and less distorted cardiac muscle fibers.
from the aforementioned data, it could be concluded that:
1- The dose used of doxorubicin 2.5 mg/kg, twice weekly for 3 weeks (cumulative 15 mg/kg) was able to induce a typical picture of cardiomyopathy model that was evident functionally, biochemically and histopathologically.
2- The concomitant use of vitamin D as a supplement with Dox treatment partially attenuate the functional and structural insults of Dox: as the prolongation of the Q-T and the depression of the systolic function were still evident.
3- Vitamin D provides its cardioprotective effects via:
a) Improving oxidative stress state of the heart.
b) Induction of HSP 20 production in the heart.
4- Relationship between vitamin D and the other cardiac HSPs & the expression of different myosin heavy chains (MHC) in normal hearts and in different pathological states remains to be identified.
5- If the partial cardiac protection obtained with concomitant vitamin D supplementation with Dox treatment can be modified (augmented or decreased) by altering its protocol i.e. given as a pretreatment and/or post treatment?
This could be a target for new researches