Renal toxicity after oral administration of lead acetate during pre- and post-implantation periods: effects on trace metal composition, metallo-enzymes and glutathione.
The present study was undertaken to compare the effects of 10-50 mg/kg b.wt. of Pb acetate after chronic treatment through oral gavage on: (a) the distribution of trace elements such as Fe, Cu, Zn, and Mn, (b) enzyme activity of delta-amino levulinic acid dehydratase (delta-ALAD) and alkaline phosphatase, and (c) glutathione (GSH) in kidney and (d) delta-ALAD in blood of pregnant and non-pregnant mice. Treatment with Pb acetate was given on every alternate day for 4 weeks prior to mating and for 3-4 weeks until pregnancy became apparent and confirmed by laporatomy. Lead administration reduced the rate of reproduction as assessed by number of living viable embryos. During normal pregnancy renal Cu, Fe and GSH tended to decline although non-significantly and continued to do so after lead administration. Mn was considerably and significantly elevated, whereas activity of delta-ALAD (non-activated) was quite low in pregnant mice. Following administration of Pb acetate, kidneys of pregnant and non-pregnant dams accumulated Pb in a dose-dependent manner, but as compared to non-pregnant mice, Pb increase in pregnant dams was significantly lower. Pb toxicity was associated with the loss of delta-ALAD in blood and kidney, but unlike the non-activated form of delta-ALAD, the dithiothreitol-activated form of delta-ALAD declined in a significant amount. The residual activity showed a high degree of negative correlation with endogenous Pb as well as with Zn/Pb ratio. Pb toxicity did not modify renal Fe, Cu, and Zn in the pregnant state, but reduced renal Fe during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)
Gupta
G S
GS
Department of Biophysics, Panjab University, Chandigarh, India.
Singh
J
J
Parkash
P
P
D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D047108:Embryonic Development; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D008670:Metals / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000623:Porphobilinogen Synthase / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects* / Q000502:physiology*; D013054:Spectrophotometry, Atomic; D014131:Trace Elements / Q000737:chemistry
D008670:Metals; D009942:Organometallic Compounds; D014131:Trace Elements; D000469:Alkaline Phosphatase; D000623:Porphobilinogen Synthase; D005978:Glutathione; C008261:lead acetate