الفهرس 
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Abstract
Cadmium is considered to be one of the most toxic substances to human health due to its wide spread in industry and subsequent release into the environment. It is clear that Cd has the ability to cause a wide spectrum of pathophysiological functions in humans, including alterations to bone metabolism, RBC production, kidney function, embryo growth and development Antioxidants play several important roles, they can inhibit free radical formation, scavenge reactive oxygen species and support normal embryonic development from early embryogenesis through protecting the embryos from free radicals and oxidative stress. Vitamin E and wheat germ oil (WGO) have been utilized in a prophylactic manner against oxidative stress.
The present study was designed to investigate the hematological and hepato-renal toxicities of cadmium in pregnant rats and their fetuses. Furthermore, the present study aimed to postulate the fetotoxicity, growth retardation, external and skeletal malformation in fetuses induced by the cadmium chloride. Also, the study was planned to evaluate the possible protective effects of vitamin E and/or wheat germ oil against cadmium chloride induced toxicity.
This study was carried out on 30 pregnant rats divided equally into five groups:
•Group1: (Control group): Each pregnant rat was orally received distilled water and 0.5 ml corn oil as vehicle daily for 13 days from 6th to 18th day of gestation period.
•Group2: (Cadmium chloride –treated group): Each pregnant rat was orally received cadmium chloride at a dose 5 mg/kg BW/day (1/20 LD50) for 13 days from 6th to 18th day of gestation period.
•group 3: (Cadmium chloride + vitamin E– treated group): Each pregnant rat was orally received cadmium chloride at a dose 5 mg/kg BW plus vitamin E intraperitoneally (Ip) at a dose 100 mg/kg BW /day for 13 days from 6th to 18th day of gestation period.
group 4: (Cadmium chloride+ wheat germ oil– treated group): Each pregnant rat was orally received cadmium chloride at a dose 5 mg/kg BW plus wheat germ oil at a dose 54 mg/ kg BW /day for 13 days from 6th to 18th day of gestation period .
group 5: (Cadmium chloride+ vitamin E + wheat germ oil - treated group): Each pregnant rat was orally received cadmium chloride at a dose 5 mg/kg BW plus vitamin E intraperitoneally (Ip) at a dose 100 mg/kg BW plus wheat germ oil at a dose 54 mg/ kg BW /day for 13 days from 6th to 18th day of gestation.
At the end of the experimental period, the pregnant rats were anesthetized on the 19th day of gestation. Blood was taken from mothers and their fetuses by the heart puncture, then placed immediately in EDTA tubes and kept on ice for hematological parameters. The other portion of the blood was centrifuged (Hettich Zeatrifugen, universal 32R Germany) and the serum was collected and stored at -20 °C till biochemical measurements. Liver and kidneys were immediately isolated from the maternal rats and their fetuses of different groups, washed with cold saline solution and kept frozen at – 80°C for biochemical measurement. The uterine horns were exteriorized through a midline abdominal incision. The number of implantation and reception sites, alive and dead fetuses was recorded and photographed by HD digital camera (10x) to examine the external visible abnormalities. One – half of the fetuses were fixed in 10% formalin and examined under stereomicroscope for the occurrence of any malformation. Fetuses were examined for skeletal malformation through staining with alizarin red S and alcian blue.
The results of the present study revealed that the oral administration of cadmium chloride induced hematological alterations as indicated by significant (P< 0.05) decrease in the values of RBCs, Hb, Ht, PLTs and WBCs in maternal rats and their fetuses. This may be attributed to that cadmium caused impairment in the synthesis of erythropoietin, a hormone whose function is to promote the formation of the red cells. On the contrary, the administration of vitamin E and/or wheat germ oil and their combinations with cadmium chloride caused remarkable significant (P< 0.05) improvement in all the measured hematological parameters. This may be due to the fact that vitamin E increases coronary and peripheral blood circulation. Also, wheat germ oil is known to contains some B complex vitamins (B6, B12 and folic acid) which are essential in the formation of red blood cells.
In addition, cadmium administration caused disturbances in the hepatic and renal functions which were reflected by significant (P< 0.05) increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as elevation of the levels of creatinine and urea. Also, the administration of cadmium chloride induced an oxidative stress in the liver and kidney tissues of rats as indicated by the significant (P< 0.05) increase in the lipid peroxidation end product (malondialdehyde, MDA) associated with significant (P< 0.05) reduction in the levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx),
On the contrary, vitamin E and wheat germ oil supplementations had significantly (P< 0.05) minimized the severity of lipid peroxidation and enhanced the activities of antioxidant enzymes (SOD, CAT and GPx) in hepatic and renal tissues as well as the content of reduced glutathione (GSH). This may be due to inhibition, by vitamin E and wheat germ oil, of the free radical induced damage to the sensitive cell membrane through scavenging the reactive oxygen radicals. Cadmium chloride was found to induce growth retardation as indicated by significant (P< 0.05) decrease in fetal body weight, body length and the number of alive fetuses as well as, frequent occurrence of dead, absorbed and malformed fetuses. This may be attributed to degeneration of the trophoblast and decidual cells, which play an important role in the transmission of nutrients to the embryo and to decrease in the uteroplacental blood flow.
In the present study, cadmium chloride caused a severe lack or retardation of bone formation in most components of fetuses’ skeleton including the skull, girdles, limb skeleton, and vertebrae. Such abnormalities may be attributed to the inhibitory action of cadmium on the cytochrome oxidase and the osteoblastic, also chondroblastic differentiation pathway in the bone marrow through direct effects on these cells. In contrast, the beneficial role of vitamin E and/or wheat germ oil in preventing or minimizing the fetal malformations may be due to the role of vitamin E as a potent anti-oxidant that protects the embryo from free radicals and the role of wheat germ oil as a factor causes increase of calcium absorption from the gut.
In conclusion, the results of the present study revealed that:
•Cadmium chloride is capable of causing marked alterations in the hematological and biochemical parameters, induction oxidative stress and inhibition of the activities of antioxidant enzymes. Also, it caused a considerable growth retardation or even mortality of the fetuses as well as caused skeletal malformations.
In contrast, the supplementation of vitamin E and/or wheat germ oil caused significant remarkable improvement in all the measured parameters including hematological and biochemical parameters as well as protected the body’s biological activities by preventing lipid peroxidation.
Furthermore, treatment of vitamin E and/or wheat germ oil can decrease the cadmium toxicity, which induced intra-uterine growth retardation (IUGR), as indicated by enhancement of the fetal growth, body weight, body length and prevention of fetal malformations.
The combination of vitamin E and wheat germ oil with cadmium chloride caused the most pronounced improvement and can prevent, to a great extent, the detrimental effect of the cadmium toxicity.