Effects of a hepato-protective agent and a hepato-secreting chelator on cadmium-induced nephrotoxicity in Syrian hamsters.
Cadmium (Cd)-induced nephropathy in male Syrian hamsters was treated with D/L-penicillamine (D/L-p) or neomynophagen C (NMC). The subcutaneous injection of CdCl(2), 3 mg/kg, three times a week led to marked renal damage, ie., increased proteinuria and the excretion of urinary N-acetyl-beta-D-glucosaminidase (NAG) as compared with the saline-injected controls. Cd-treated hamsters that were injected intraperitoneally with D/L-p, 0.1 mg/kg, five times a week, showed less renal damage, including a reduction in urinary protein from 3.60 + or - 0.42 to 1.77 + or - 0.7 mg/d. NMC-treated hamsters showed a reduced excretion of NAG (from 1.47 +/ - 0.34 to 0.91 + or - 0.68 u/d). The concentration of Cd in renal cortical tissue was reduced slightly (from 2.78 + or - 0.08 to 2.34 + or - 0.3 mg/g.prot) by NMC treatment, but not by D/L-p. The elevated malondialdehyde (MDA) in renal cortical tissue was unaffected by administering D/L-p or NMC. The concentration of glutathione (CSH) in the renal cortex was not elevated after administering Cd, but the ratio of the reduced to the oxidized GSH was elevated. The Cd induced liver dysfunction, as compared with untreated controls. The dysfunction was improved slightly by NMC administration, but not by that of D/L-p. Changes in renal morphology induced by Cd involving marked degeneration and necrosis of tubules as shown by light microscopy, were unaffected by treatment with D/L-p or NMC. We thus demonstrated the efficacy of D/L-p of NMC in treating the nephropathy induced by Cd in hamsters. The mechanism of therapeutic effect is not known.
Shibasaki
T
T
Second Department of Internal Medicine, The Jikei University School of Medicine, Nishi-Shimbashi, Minato-ku, Tokyo 105, Japan.
Matsumoto
H
H
Gomi
H
H
Ohno
I
I
Ishimoto
F
F
Sakai
O
O
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity* / Q000652:urine; D002105:Cadmium Poisoning / Q000188:drug therapy*; D002273:Carcinogens / Q000633:toxicity*; D002614:Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006224:Cricetinae; D005978:Glutathione / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008647:Mesocricetus; D009392:Nephrectomy; D010084:Oxidation-Reduction; D010396:Penicillamine / Q000008:administration & dosage / Q000627:therapeutic use*; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy
D002273:Carcinogens; D002614:Chelating Agents; D008315:Malondialdehyde; D000118:Acetylglucosaminidase; D005978:Glutathione; D010396:Penicillamine; D019256:Cadmium Chloride