الفهرس 
AcknowledgmentOnly 14 pages are availabe for public view
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Abstract
Exposure to KBrO3 may occur during its production and uses as a dough conditioner, food additive and in some drinking-water samples as a by-product of ozone disinfection. Bromate and its metabolite bromide are actively transported by the sodium iodide transporter protein found in the kidney. Most studies investigating the mechanism of KBrO3-induced carcinogenicity have focused on DNA damage due to oxidative stress. So, the current study was carried out to investigate the nephrotoxic effect of KBrO3 in female rats and the preventive roles of curcumin and bone marrow stem cells as antioxidants and anti-apoptotic agents. Thirty two female rats weighing 140+10 gms were classified randomly into four groups 10 rats each. The 1st drank tap water only as control group, the 2nd exposed to KBrO3 (100mg/kg body weight) in drinking water for four weeks, 3rd was exposed to KBrO3 like group 2 with co-treatment with curcumin (100 mg/kg body weight, ip) twice a week for four weeks, the 4th group was exposed to KBrO3 like group 2 and 3) and co-treated with BM-MSCs (1x106 cells) once a week for four weeks. After the end of treatments rats were sacrificed for collection of blood and kidneys for biochemical and histological studies. Sera were separated and used for measuring kidney function and oxidative stress markers. Parts of kidney’s were fixed in formal alcohol for histological, histochemical and TUNNEL studies. Other parts of kidney were stored at -800C for extraction of RNA and determination of caspas 3 gene expression by real time PCR.
The results showed that:
First orally administration of KBrO3 caused
• A significant increase in the levels of BUN, creatinine, uric acid, and the activitities of AST and ɤGT in serum compared to the control group.
• Oxidative stress as shown by significant increase in the level of LPO and NO and a significant decreases in the level of TAC, Vit C, Vit E, GSH and the activities of SOD and CAT in serum compared to the control group.
• Increases in the % of apoptotic cells as shown by TUNNEL assay in the kidney cortex and medulla compared to the control group.
• Increase in the gene expression of caspase 3 two fold relative to the house keeping gene (GAPDH) as identified by real time PCR.
• Histological changes such as necrosis, atrophy of the glomeruli, congestion, atrophy with peri-glomerular fibrosis, and disorganization of the epithelial lining of renal tubules. Basement membrane of the Bowman’s capsules and tubular basement membrane showed PAS positive material. In addition, Mallory’s triple stain showed peri-glomerular fibrosis.
Second co-treatment of rats with CUR and BM-MSCs results in:
• Normalization of the kidney function parameters in serum.
• Improvement in the oxidative stress parameters in serum, except the activity of CAT which increased than the control and BKrO3 treated groups.
• Decrease in the % of apoptotic cells in comparison to the KBrO3treated groups but still higher than the control group.
• The gene expression of caspase 3 was higher in the CUR co-treated groups than all the other groups.
• Improvement in the histological structure of kidney but still presence of congestion, dilatation of some renal tubules, tubular nephrosis, thickening of the brush border of the renal tubules and slight increase in the interstitum connective tissue.
In conclusion, orally exposure of rats to KBrO3 induced histological change in kidney and biochemical alterations in serum such as kidney function and oxidative stress markers with elevation of apoptotic cells, especially in kidney cortex and the increased of casease 3 gene expression. Co-treatment of KBrO3-intoxicated rats with both CUR and BM-MSCs improved the histological changes and ameliorated the biochemical parameters except the expression of caspase 3 gene expression which still higher in CUR treated group compared to the other 3 groups.