Cadmium exposure in mice (8 mg Cd as CdCl 2 /kg bw, for 8 weeks, daily oral) resulted in increased cadmium levels in kidney and liver. The level was quite high in kidney (3 times) as compared to liver. However when selenium (0.35 mg Se as Na 2 SeO 3 /kg bw, daily, orally for 8 weeks) was administered concurrently, a significant decrease in cadmium level was seen in kidney and liver.Cadmium exposure resulted in apparent pathological changes in the proximal convoluted tubules (PCT) in kidney at the electron microscopic level. The mitochondria seem to be most severely affected among the cellular organelles. The alterations included swelling and dilation of the organelles. The cristae showed a disorganized architecture. Activities of the antioxidant enzymes glutathione peroxidase (GSH-Px) and catalase in kidney were also significantly inhibited. However, when selenium was co-administered, the structural integrity of the PCT was comparable to the control. The activity of the antioxidant enzymes was also restored to normal levels.This study suggests that cadmium manifests toxic effects by disrupting the antioxidant enzyme system, which in turn affects the membranous structures such as mitochondria and endoplasmic reticulum. This, in turn, affects the oxidative phosphorylation. Further, it is observed that the co-administration of selenium diminishes the effects of cadmium.

The mechanism of the antagonistic behaviour of selenium (Se) against cadmium (Cd) toxicity is investigated. This study reports the distribution of Cd at the organ and subcellular level after chronic treatments. The possible role of the selenium binding proteins (SBP) during Cd exposure are also evaluated. Kidney concentrates more Cd than liver following 8 weeks of treatment. Simultaneous administration of Se reduced Cd accumulation in Kidney. This affect did not occur in liver. Among the subcellular fractions, the maximum concentrations of both of the elements were found in the cytosol. The overall uptake of 75Se was enhanced in the cytosol of kidney and liver of the Cd treated animals. These observations support a hypothesis that selenium is complexed with cadmium. The increase in the labeling of SBP as a result of Cd exposures may reflect a change in the conformation of the protein molecule. These proteins (SBP) contain a sequence motif, which may be an active redox centre. Also, Cd significantly reduced the glutathione level, thereby disrupting the thiol/disulfide balance. This in turn may affect the redox status of the proteins leading to a 75Se or 75Se-Cd complex with SBP.

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Cadmium exposure in mice (8 mg Cd as CdCl2/kg bw, for 8 weeks, daily oral) resulted in increased cadmium levels in kidney and liver. The level was quite high in kidney (3 times) as compared to liver. However when selenium (0.35 mg Se as Na2SeO3/kg bw, daily, orally for 8 weeks) was administered concurrently, a significant decrease in cadmium level was seen in kidney and liver. Cadmium exposure resulted in apparent pathological changes in the proximal convoluted tubules (PCT) in kidney at the electron microscopic level. The mitochondria seem to be most severely affected among the cellular organelles. The alterations included swelling and dilation of the organelles. The cristae showed a disorganized architecture. Activities of the antioxidant enzymes glutathione peroxidase (GSH‐Px) and catalase in kidney were also significantly inhibited. However, when selenium was co‐administered, the structural integrity of the PCT was comparable to the control. The activity of the antioxidant enzymes was also restored to normal levels. This study suggests that cadmium manifests toxic effects by disrupting the antioxidant enzyme system, which in turn affects the membranous structures such as mitochondria and endoplasmic reticulum. This, in turn, affects the oxidative phosphorylation. Further, it is observed that the co‐administration of selenium diminishes the effects of cadmium. J. Trace Elem. Exp. Med. 10:233–242, 1997. © 1997 Wiley‐Liss, Inc.

The antiprotozoal drug metronidazole, when administered orally at a dose level of 100 mg/kg body wt. daily for 7 days to rats, brought about significant elevation of renal brush-border-membrane-bound hydrolytic enzymes, such as alkaline phosphatase, maltase, sucrase, and leucine aminopeptidase (LAP). Kinetic analysis of the enzymes (substrate saturation) indicated that the drug produced an increase in the maximum of apparent initial enzyme velocity (Vmax), while the substrate affinity constant (Km) remained unaltered. These changes were not recovered to the normal level even after the drug regimen was stopped and the animals were allowed to recover for a period of 7 days. Lipid analysis of brush border membrane (BBM) revealed a significant elevation in the cholesterol, phospholipid, and ganglioside levels, while no marked change was recorded in triglyceride, free fatty acid and plasmalogen. Study of the temperature-dependent parameters of the enzymes showed that metronidazole induced a shift in the transition temperature (To) in LAP with nearly total reversibility in the recovery group. No such change was seen in the other enzymes. However, there also was a lowering in the energy of activation (Ea) below To, which returned to normal after the treatment was withdrawn.