الفهرس 
Introduction and aim of the work
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Abstract
The present work was aimed to study the risk of OTA exposure on the kidney by studying the following aspects: Determination of ochratoxin A in food, blood and urine of individuals from Kafr ElHessa village, a suburb of Mansoura city, as a survey analysis for a rural area in Egypt. Determination of oxidative stress; as determined by measuring serum malondialdehyde (MDA) concentration as a lipid peroxidation, antioxidant enzymes; as determined by measuring serum superoxide dismutase (SOD) and catalase activities. In addition, determination of dietary vitamins; by measuring serum vitamin E and A concentrations in individuals exposed to ochratoxin A. Determination of urinary Nacetyl Dglucose aminidase (NAG) as a marker of kidney tubular dysfunction in individuals exposed to OTA. In vitro determination of ochratoxin Ainduced apoptosis in human neutrophils. In vitro determination of ochratoxin Ainduced cytotoxicities on African monkey kidney (Vero) and rat hepatic stellate (HSCT6) cell lines. The results revealed that: Ochratoxin A was found in 37.8% of food samples (n=45) collected from Kafr ElHessa village with 37% of wheat samples and 38% of rice sample were found to be contaminated with OTA. Also, 89.9% of blood sample (n=308) were found to be contaminated with OTA. OTA was detected in 89% of male and 91% of females blood sample at average concentration of 0.45 and 0.54 ng/ml, respectively. 81.6% of male and 75.3% of female blood samples contains OTA at concentration 0.10.99 ng/ml. While 7.79% of male and 15.6% of female blood sample were contaminated with above 1ng/ml concentration of OTA. Furthermore, the results revealed that for age less than 25 years, and at concentration of OTA from 0.1 to 0.99 ng/ml, the percentage of contaminated samples with OTA (in relation to all samples) in males (81.13 %) is higher than the percentage of contaminated samples with OTA in females (79.4 %). Also, for age between 2539, and >=40 years, the same higher percentages are found in males (82.7 and 79.59 %, respectively) than females (73.91 and 68.57 %, respectively). While the percentages for concentration of ochratoxin A above 1ng/ml (in relation to all samples) are higher in females (17.78, 13.0 and 14.28 %, respectively) than males (5.65, 11.53 and 6.12 %, respectively) at the designated age. Also, OTA was detected in 86.6% of male and 84.3% of female urine samples. 55% of the male samples and 53.21% of the female samples were detected at concentration range 0.10.99 ng/ml. While 31.66% of the male samples and 31.24% of the female samples were fall in concentration above 1 ng/ml. Moreover, the results revealed that for age less than 25 year, the percentage of contaminated samples with OTA (in relation to all samples) in females 46.3% was higher than the percentage of contaminated samples with OTA in males (26.9%). On the contrary, for age between 2539 and >=40 years, the higher percentage values were found in males (38.4 and 34.6 %, respectively) than females (27.8, and 25.9%, respectively) at the designated age. The index values of ochratoxin A concentration between mean serum concentration and mean urine concentration revealed that the results showed that, for age less than 25 year, the value of index was 0.28, and for age between 2539 and >=40 year, the values of index were 0.38 and 0.40, receptively at the designated age. The results of correlation between concentrations of OTA in 124 human blood serum and the corresponding urine samples grouped by age revealed that there was positive correlation between serum and urine samples, for age less than 25 year, there was positive correlation between serum and urine samples. Also, for age between 2539 year, there was positive correlation between serum and urine in 124 samples.The results of oxidative stress and antioxidant enzymes revealed that there was a nonsignificant increase in the mean of malondialdehyde (MDA), vitamin E and vitamin A concentrations in high OTA serum group with respect to low OTA serum group. On the other hand, there was a nonsignificant decrease in superoxide dismutase (SOD) and catalase activities of high OTA serum group than low OTA serum group. The results of vitamin E and A revealed that the mean concentration of vitamin E and A in all individuals were found in the normal range with nonsignificant increase of mean concentration of vitamin E and A in group of high OTA in their sera than low OTA group. The results of urinary enzyme (NAG) showed that there was a significant increase in the mean of urinary NAG activity of high OTA group with respect to low serum OTA group. The results of in vitro effect of different concentrations ochratoxin Ainduced apoptosis on cultured human neutrophils revealed that there was significant increase in the percentage of apoptosis in human neutrophils incubated for 72 hours with different concentrations of OTA ranging from 0.5 to 8.0 ng/ml. The results of cytotoxic effects of OTA, extracted from blood, urine and standard OTA on cultured mammalian cell lines of Vero and hepatic stellate T6 cell lines revealed that all the concentrations induce cytotoxic effect, the lowest serum, urine and standard OTA that induce this cytotoxicity were 0.22, 0.27, and 0.1 ng OTA/200 l, respectively. The mechanism of OTA induced cytotoxicity is lipid peroxidation, by oxygen continues in a chain of radical reactions, as consider one of the manifestation of cellular damage in the toxicity of OTA. OTA protection mechanisms in vivo includes a complex array of endogenous antioxidant enzymes, numerous endogenous antioxidant factors including glutathiones (GSH) and other tissue thiols, haem proteins, coenzymes Q, bilirubin and urates, and a variet of nutritional factors, primarily the antioxidant vitamins such as vitamin C, vitamin E, carotene (precursor of vitamin A) and retinoids. Key Words: (not more than Ten) Ochratoxin A, Mycotoxins, HPLC, Antioxidants, Apoptosis, Cytotoxicity.