Lead is being a wide environmental contaminant due to its significant role in modern industry. Lead poisoning among pregnant women is a significant public health probleam, as it affects development. Lead produces oxidative damage in the kidney as evidenced by enhancing lipid peroxidation product in kidney tissue. Curcumin is a well known biologically active compound which has been shown to ameliorate oxidative stress and is considered to be a potent antioxidant .Vitamin C, a known chelating agent which has the ability to chelate lead with non-enzymatic antioxidant features and it was widely reported to have the ability to protect cells from oxidative stress.
This work was designed to study the histological and ultrastructural changes in the kidney of rat pups at 18th , 20th day of gestation and at weaning after oral intake of lead acetate to the pregnant rats from the first day of pregnancy till weaning and to investigate the effects of using the protective role of curcumin and vitamin C against the effects of lead acetate on the kidney of rat pups.
Forty-eight adult female albino rats were allowed to be pregnant and were divided into two equal groups: control group and exprimental group.
The control group was divided into four subgroups. Each subgroup contains six pregnant rats . Also, the exprimental group divided also into four subgroups. Each subgroup contains six pregnant rats. The 1st sub- group was lead acetate treated group had administrated lead acetate 10mg/Kg/ day orally by gastric tube from the 1st day of pregnancy till weaning .The 2nd subgroup was lead acetate plus curcumin group had administrated lead acetate 10mg/Kg/ day orally and curcumin 100mg/Kg/ day orally by gastric tube from the 1st day of pregnancy till weaning . The 3rd subgroup was lead acetate plus vit C group had administrated lead acetate 10mg/Kg/ day orally and vit C 140mg/Kg/ day orally by gastric tube from the 1st day of pregnancy till weaning . The 4th subgroup was lead acetate plus curcumin & vit C group had administrated lead acetate 10mg/Kg/ day plus curcumin 100mg/Kg/ day and vit C 140mg/Kg/ day orally by gastric tube from the 1st day of pregnancy till weaning.
Two pregnant rats from each subgroup of the control and experimental were anaesthetized using ether inhalation. The abdominal wall was incised and the uterus was opened and the fetuses were extracted then the abdomen of each fetus was opened and the kidneys were extracted. This was done on 18th day of gestation and on 20th day of gestation.
The outcome of the remaining two pregnant rats from each group will be sacrified at weaning (2weeks after birth). The abdomen of each offspring was opened and the kidneys were extracted.
The extracted kidneys of these subgroups were then prepared for light and electron microscopic study.The kidney specimens for light microscopic study would be stained by Haematoxylin and eosin and Masson's trichome stain .
In the control group, light microscopic examination of the renal cortex of fetal rat aged 18 days showed subcapsular zone containing the immature forms of renal developmental stages in the form of renal vesicle, comma shaped , S shaped bodies and immature glomerulus which appeared as dense rounded structure. While in Fetal rats on 20th day of gestation the renal cortex contained mature glomerulus with appearance of renal space , the proximal tubules consisted of columnar cells with rounded basal nuclei .In neonatal rats at weaning the mature glomeruli had parietal layer, visceral layer and renal space in between . The proximal tubule consisted of columnar cells with rounded basal nuclei .The distal tubules had low cubical cells with wide lumen.
By electron microscopic examination of all ages , the cells lining the proximal convoluted tubule had a single rounded nuclei . Its cytoplasm contained many mitochondria. These cells had many microvilli at its apical surfaces. Its lumen was obliterated by microvilli. The cells lining the distal convoluted tubules showed few microvilli at its apical part of cells. The cells had large nuclei occupying much more of the cell .The cytoplasm of these cells contained few mitochondria . The glomerular filter consisted of three components from inward to outward : fenesterated capillaries endothelium, glomerular basement membrane and foot processes of podocytes.
The lead acetate treated groups showed desquamation of cells of the proximal convoluted tubules which were dilated and the lining epithelium was flattened and also the distal convoluted tubule were degenerated. The glomeruli were intact. Rats at weaning showed degenerated glomeruli with wide renal space.
By electron microscopic examination the cells lining the proximal tubule contained vacuolated mitochondria , their microvilli were few and the lumen was wide , the cells lining the distal tubules had small sized , shrinked nucleus ,the cytoplasm showed multiple vacuoles .The mitochondria were degenerated and in the form of clusters .The lumenal surface of these cells were irregular.
The administration of curcumin with Lead acetate to pregnant and lactating rats showed that some proximal tubules were dilated and its lining epithelium was compressed. Other proximal tubules were intact. some distal tubules showed degeneration.
By electron microscopic examination some cells lining the proximal tubules showed shrinked nucleus and its cytoplasm had multiple vacuoles. The other cells appeared intact with heterochromatic nucleus. The glomerular filter had small areas of thickening in the basal lamina and the foot process were broad and thick and showed adhesions between them.
In lead acetate plus vitamin C treated group some proximal tubules showed degeneration and vacuolation of its lining cells, other tubules were intact. The glomeruli also showed degeneration.
By electron microscopic examination, the cell lining the proximal tubule showed normal nucleus. Its cytoplasm contained multiple vacuoles and intact mitochondria. The microvilli were intact and projected in its lumen which obliterate it. The cells lining the distal tubule showed shrinked nucleus with indentation. The cytoplasm was vacuolated. Some mitochondria were intact. The luminal border of these cells was irregular with scanty microvilli.
In lead acetate plus curcumin and vitamin C treated group the glomeruli were intact but its renal space was wide , the proximal and distal tubules appeared like normal .
By electron microscopic examination there were signs of improvement. The cell lining the proximal tubule was cuboidal in shape. It had rounded nucleus and elongated mitochondria. The microvilli were condensed and project in its lumen. The cell lining The distal tubule had large nucleus , its cytoplasm showed elongated intact mitochondria The glomerular filter consisted of basal lamina with regular thickness and the foot process had slit pores between them.
Conclusions
Lead acetate affects the kidney of the developing rat during gestation and lactation periods. Lead produces oxidative damage in the kidney Therefore, exposure to lead acetate, either occupationally or through the diet, must be restricted, especially during pregnancy and lactation. In addition, increasing awareness of its hazards is recommended . Curcumin is a well known biologically active compound, has been shown to ameliorate oxidative stress and it is considered to be a potent antioxidant
Also vitamin C is a known chelating agent with non-enzymatic antioxidant features, was widely reported to have the ability to protect cells from oxidative stress in lead-exposed rats, adminstiration of a combination of curcumin and vitamin C minimize the harmful effect of lead acetate on developing kidneys.
Recommendations:
Oral administration of a combination of curcumin and vitamin C to females during pregnancy minimize the harmful effect of lead acetate on developing kidneys.
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