الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
Doxorubicin (DOX), a strong anticancer drug, induces toxicity to different organs especially the heart, liver and kidney.This limits its therapeutic usage in cancer treatement.
Doxorubicin-induced cardiotoxicity occurs by oxidative stress with free radical production, apoptosis and inflammation. This toxic effect of doxorubicin on heart could be reduced by many natural substance as silymarin which is a polyphenolic flavonoid that is extracted from silybum marianum. It has antioxidant, anti-inflammatory and antiapoptotic characteristics that make silymarin a protective agent to many organs such as liver , heart and brain.
Silymarin has showed promise in animal and human studies, but its low water solubility and bioavailability restrict its therapeutic usage, so nano-based phytomedicine formulations have been produced to improve silymarin solubility, bioavailability and stability to obtain better protective effect.
The aim of this study was to assess a comparison between the possible protective effect of silymarin and its nanoparticles on DOX- induced cardiotoxicity and their possible mechanisms of action.
The study was carried on 32 adult male albino rats. The animals were randomly divided equally into 4 groups as follows: Control group: 8 rats divided into three groups, subgroup A (2 rats) received single dose of 10 ml/kg saline intraperitoneally , subgroup B (3 rats) received 200 mg /kg silymarin dissolved in distilled water once per day orally by gavage for 12 days and subgroup C (3 rats) received 200 mg /kg SiNPs dissolved in distilled water once per day orally by gavage for 12 days. Doxorubicin group (Dx-group): 8 rats received single dose of 10 mg/kg doxorubicin intraperitoneally . Silymarin treated group (S-group): 8 rats received 200 mg /kg silymarin dissolved in distilled water once per day orally by gavage for five days before injection of doxorubicin and was continued seven days later . Nano-Silymarin treated group (NS- group): 8 rats received 200 mg /kg SiNPs dissolved in distilled water once per day orally by gavage for five days before injection of doxorubicin and was continued seven days later.
• Animals were sacrificed on the seventh day after doxorubicin injection in the Dx-group,S-group and NS-group and by this animals from control group were sacrificed on the twelfth day after the begin of the experiment.
The main results of the study revealed that:
Biochemical study:
• There was a significant increase in the tissue levels of MDA and a significant decrease in the tissue levels of GSH in the Dx-group compared to the control group while there was a significant decrease in MDA levels and a significant increase in GSH levels in both the S-group and the NS-group compared to Dx-group with no significant difference in these levels among the S-group and the NS-group .
• There was a significant increase in the serum leves of CK-MB, LDH AST and ALT in Dx- group compared to the control group while the S-group and the NS-group showed a significant decrease in the serum levels of these parameters compared to the Dx-group. Interestingly these levels showed a significant decrease in the NS-group compared to the S-group.
• Histological study:
(1) Light microscopic study:-
(A)Hematoxylin and Eosin stained sections:
Dx-group showed disturbed normal structure of cardiomyocytes; some cardiac muscle fibers showed strong acidophilic homogenous cytoplasm with pyknotic deeply stained nuclei (apoptotic figures), fragmented muscle fibers, vascular congestion and inflammatory cells infiltration. S-group revealed an improvement in the histological findings but still showing some degenerated cardiac muscle fibers. NS-group: Better improvement was observed in the histological findings of the NS-group than the S-group; apparently normal cardiac muscle fibers as control group.
(B)Immunohistochemical study:
Immunohistochemical study of activated-caspase 3 and IL-6 showed a significant increase in their expression in the Dx-group compared to control group. While there was a significant decreased in expression of both in the S-group and the NS-group. However there was a significant decrease in their expression in the NS-group compared to the S-group.
(2) Transmission electron microscopic study: -
Dx-group showed disturbed normal structure of cardiomyocyte as revealed degenerated myofibrils, peripherally located nuclei, degenerated mitochondria, sarcoplasmic vacuoles , dilated sarcoplasmic reticulum and blebbing of sarcolemma. S-group showed relative improvement in these findings.However there were some degenerated myofibrils,some degenerated mitochondria and few areas with blebbing of sarcolemma still present in this group NS-group showed better improvement in EM findings than the S-group as showed apparently normal structure of cardiomyocytes as control group.
These findings revealed that DOX chemotherapy could induce chemical and histological alterations in cardiomyocytes while silymarin could improve these alterations and SiNPs gave the most favorable results.