الفهرس 
Introduction and review of literatureOnly 14 pages are availabe for public view
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Abstract
Hormonal therapeutics are treatments of cancer. Tamoxifen, a nonsteriodal antiestrogenic drug, is mainly used in the treatment of breast cancer. However, it was found to result in many side effects in human and experimental models.
Medical plants are widely used as traditional drugs against various diseases. Curcumin is one of the most common herbs used in traditional foods and medicine. It has a wide range of beneficial properties including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity.
The present study adopted two integrated aspects. The first to investigate the possible side effects of tamoxifen, as a nonsteriodal antiestrogenic drug, in female albino rats after daily treatment for different periods (three, six and nine consecutive weeks). The second to investigate the ameliorative effect of curcumin against tamoxifen induced toxicity. Therefore, the target organs were liver and kidney and the used approaches were histological, histochemical, immunohistochemical and biochemical.
Animals groups:
Animals were divided equally into four groups, each contained 18 animals:
group I (control groups):
Animals of this group were served as control groups. They were given the standard diet and tap water only.
group II (Curcumin groups):
Rats of this group were orally given curcumin (150 mg/kg body weight) daily for nine weeks.
group III (Tamoxifen groups):
Animals of this group were orally received tamoxifen at a dose level of 20 mg/kg body weight daily for nine weeks.
group IV (Tamoxifen and curcumin groups):
Animals of this group were orally received tamoxifen (20 mg/kg body weight) then after two hours they orally given curcumin (150 mg/kg body weight) daily for nine weeks.
After three, six and nine weeks, six animals from each group were sacrified.
After dissection, liver and kidney were immediately removed and were fixed in alcoholic Bouin’s fluid for the histological investigations and demonstration of polysaccharides and 10% neutral formalin for demonstration of total proteins, nucleic acids and immunohistochemical staining of Ki-67 and α-SMA.
After fixation, specimens were dehydrated in ascending series of ethyl alcohol, cleared into two changes of xylene, infiltrated in three changes of molten paraffin wax with melting point of 58-60oC and then embedded in molten paraffin. Sections of 5 microns thickness were cut by using rotary microtome. For histological examination, sections stained with Ehrlich’s hematoxylin and counterstained with Eosin. For histochemical procedures, polysaccharides were demonstrated by periodic acid-Schiff reaction, total proteins by mercury bromophenol blue method and nuclei acids by Schiff-methylene blue method. Immunohistochemical staining and image analysis of both α-SMA and Ki-67 were detected.
For biochemical analysis, blood samples were collected in clean centrifuge tubes and left to clot at room temperature and then sera were separated by centrifugation at 3000 rpm for 20 minutes. The collected sera were stored at -20°C until analysis. The activities of ALT, AST, CAT and SOD were determined. Besides, the level of urea, creatinine, MDA and GSH were measured.
The results of this study included:
Animals treated with curcumin only showed no changes in the histological, histochemical and immunohistochemical observation of liver and kidney and biochemical investigations in sera of these rats.
I- Liver:
The histological observations of rats treated with tamoxifen showed loss of the normal architecture of hepatic lobules. Moreover, congestion and dilation of veins, bile duct proliferation, leukocytic infiltration, activated Kupffer cells, cytoplasmic vacuolation, pyknotic nuclei and fatty infiltration were detected. Marked improvement of all these pathological changes was observed in animals treated with tamoxifen and curcumin.
Histochemically, gradual depletion in polysaccharides, total proteins and RNA contents was observed in liver of rats treated with tamoxifen. On the other hand, restoration of theses contents was observed in hepatic tissues of rats treated with tamoxifen and curcumin.
Immunohistochemically, an increase in the expression of α-SMA and Ki-67 was observed in liver of rats treated with tamoxifen only. Meanwhile, administration of rats with tamoxifen and curcumin showed reduction in the expression of both α-SMA and Ki-67 and appeared nearly similar to control group
II- Kidney:
Animals treated with tamoxifen showed many histological changes in the cortex during the different periods. Atrophied glomeruli, widened urinary spaces, dilated and degenerated convoluted tubules, leukocytic infiltration, enlarged and congested blood vessels, hyaline proteinaceous casts, edema, pyknotic nuclei and cytoplasmic vacuolation were observed. On the other hand, an improvement of all these changes was observed in kidney of rats treated with tamoxifen and curcumin.
Histochemically, treating animals with tamoxifen only showed gradual depletion in polysaccharides, total proteins and RNA contents in the renal cortex. Meanwhile, rats treated with tamoxifen and curcumin showed gradual restoration of all these contents.
Immunohistochemically, strong expression of α-SMA and Ki-67 was observed in kidney of rats treated with tamoxifen only. Meanwhile, rats treated with tamoxifen and curcumin showed slight or weak expression of α-SMA and Ki-67.
III- Biochemical analysis:
In the present work, the oral administration of tamoxifen induced elevation in the activities of the liver enzymes (ALT and AST) and in the level of urea, creatinine and MDA. In addition, reduction in the activities of CAT and SOD as well as the level of GSH in sera of treated rats was also recorded. On the other hand, in rats treated with tamoxifen and curcumin, significant reduction in the activities of ALT and AST and in the levels of urea, creatinine and MDA was recorded. Besides, an increase in the activities of SOD, CAT and the level of GSH was estimated, comparing with animals treated with tamoxifen alone.
Conclusion:
In conclusion, curcumin has ameliorative effect on the histological, histochemical, immunohistochemical and biochemical changes induced by tamoxifen in liver, kidney and biochemical parameters in rats.
Recommendations:
The results of the present study showed that curcumin has ameliorative effects against the different side effects of tamoxifen. So, we recommended the usage of curcumin during administration with tamoxifen drug treatment of breast cancer.