الفهرس 
AbstractOnly 14 pages are availabe for public view
 |  | from | 179 |  |  |
| | | from | 179 | | |
Abstract
The present study was designed to investigate the nephroprotective effect of cerium oxide nanoparticles (CeO2NPs) on cadmium toxicity in rats through the evaluation of hematological parameters and serum biochemical constituents. Histopathological changes of kidney were also evaluated. One hundred and twenty male albino rats were divided into six groups (each one 20rats)as follows; control (C), NC0.1, NC0.5, cadmium (Cd), Cd+NC0.1 and Cd+NC0.5 groups.
group (C) rats were received balanced diet and distilled water orally and kept as control group. Rats in the NC0.1 and NC0.5group were injected i.p with CeO2NPs at a dose of (0.1 mg/kg and 0.5 mg/kg b.wt), respectively twice weekly for 2 weeks from the 15th day till the end of the study. In group (Cd) rats were received CdCl2 by oral gavage daily (10 mg/kg b.wt) for 28 days. group (Cd+NC0.1 andCd+NC0.5) rats were given CdCl2 by oral gavage (10 mg/kg b.wt) for 28 days and injected i.p with CeO2NPs at a dose of (0.1 mg/kg and 0.5 mg/kg b.wt), respectively twice weekly from the 15th day till the end of the study.
The experiment extended for 28 days through which the weighing of rats and collection of samples was done. Whole blood samples were collected on the15th, 21st and 28th days for hematological examination. Sera were collected from all groups on the 7th, 15th, 21st and28thdays for estimation of the biochemical constituents. Urine samples were collected on the15th, 21st and 28th days for complete urine analysis and ELISA determination of MAU. Kidney samples were removed rinsed in normal saline and fixed in neutral formalin10% for histopathological examination. Homogenate of kidney was used for estimation of the oxidant/antioxidant parameters and estimation of the mRNA levels of the NBN and Nrf2 genes.
Hematological examination included RBCs count, Hb concentration, PCV%, MCV and MCHC values, TLC, differential leucocytic count and PLT count. While the biochemical parameters included serum TP, albumin, globulin, A/G ratio, TC, TGLDL-C, HDL-C, urea, creatinine, sodium, potassium, total calcium, phosphorus, ELISA determination of Cys-C, β2-MG, KIM-1 and IL-1β, oxidant/antioxidant contents include SOD and GSH, MDA level were evaluated. Urine analysis includes complete urine analysis and ELISA determination of MAU. Real time quantitative PCR analysis of the mRNA levels of the NBN and Nrf2 genes.
In comparison to the mean values of the control group, the following results were observed:
Groups (NC0.1 and NC0.5): revealed non-significant changes in the hemogram, protein profile, lipid profile, urea, creatinine, electrolytes and minerals, ELISA parameters, urine analysis, oxidant/antioxidant parameters, gene expression of the NBN and Nrf2 and normal structure of renal tissue except the NC0.5group revealed increased PCVon the 21st day, decreased serum protein on the 28th day and decreased lipid profile on the 28th day.
group (Cd): revealed normocytic normochromic anemia, significant decrease in the erythrogram including the RBCs count, PCV% and Hb concentration, significant leucocytosis accompanied by lymphocytosis on the 15th day, significant leucopenia associated with lymphopenia on the 21st and 28th days, significant thrombocytopenia, significant decrease in the serum proteins, albumin, globulins, HDL-C, sodium, SOD, GSH and Nrf2 levels, significant increase of the serum TC, TG, LDL-C, urea, creatinine, potassium, total calcium, phosphorus, Cys-C, β2-MG, KIM-1, IL-1β, and MAU, MDA and NBN levels. Abnormal urine picture was confirmed from turbid dark yellow urine, with significant proteinuria, glucosuria, bilirubinuria, many RBCs and pus cells associated with crystaluria throughout the experimental period.
Groups (Cd+NC0.1 and Cd+NC0.5):nanoceria ameliorated the adverse effect of cadmium through non- significant decrease in the erythrogram include RBCs count, PCV% and Hb concentration, significant increase in the leucocytes and lymphocyte, serum proteins, albumin, globulins, HDL-C,SOD, GSH and Nrf2, significant decrease in the platelet count, TC, TG and LDL-C, urea, creatinine, potassium, total calcium, phosphorus, Cys-C, β2-MG, KIM-1, IL-1β, MAU, MDA and NBN. Few calcium phosphate crystals with few RBCs and pus cells in urine samples on the 21st and 28th days.
Conclusion:
from the present study, it is concluded that:
1. Cadmium exposure is one of the nephrotoxic metals that cause renal damage as indicated by changes in the hemogram, serum biochemical parameters, urine analysis, gene expression and histopathological examination.
2. Nanoceria is biologically safe and has a nephroprotective effect against the cadmium toxicity.
3. The nephroprotective efficacy of CeO2NPs against renal injury obtained by cadmium toxicity was mediated by inhibition of inflammatory markers, improvement in kidney function tests and upregulation of genes related to antioxidant and downregulation of the apoptotic gene.
4. The protective and therapeutic effects of cerium oxide nanoparticles at higher dose (0.5mg/kgb.wt) were more effective than lower dose (0.1mg/kgb.wt).