Effect of L-ascorbic acid pretreatment on cadmium toxicity in the male Fischer (F344/NCr) rat.
Some studies have indicated that cadmium-induced lethality and selective injurious effects to specific tissues, such as testes or liver, can be prevented by pretreatment with the antioxidant L-ascorbic acid (ascorbic acid). However, the basis of this tolerance is unclear. We examined the effects of ascorbic acid pretreatment on cadmium toxicity in male Fischer (F344/NCr) rats. Cadmium treatment alone (25 mumol CdCl2/kg, s.c.) proved lethal, causing a 93% mortality within 72 h, but in rats pretreated with ascorbic acid (2 g/kg, s.c. 24, 12 and 1 h) cadmium-induced lethality was nearly prevented. Hepatic lesions, including hepatocellular necrosis, induced by cadmium were at least partially ameliorated by ascorbic acid pretreatment. Ascorbic acid pretreatment had no effect on cadmium-induced testicular lesions nor on cadmium content in testes, liver, kidney and urine. Ascorbic acid alone modestly increased hepatic metallothionein (MT), but not renal MT and had no effect on induction of hepatic or renal MT by cadmium. In contrast to liver and kidney, testicular cadmium-binding protein (TCBP) in rats exposed to cadmium alone decreased markedly. Moreover, the level of TCBP decreased unexpectedly in ascorbic acid pretreated rats as compared with control. These results indicate that ascorbic acid pretreatment decreases the toxicity of cadmium in the rat without markedly modifying its toxicokinetics or markedly stimulating MT synthesis.
Shiraishi
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N
Inorganic Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201.
Uno
H
H
Waalkes
M P
MP
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001483:Base Sequence; D002105:Cadmium Poisoning / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; C004203:cadmium-binding protein; D008668:Metallothionein; D007770:L-Lactate Dehydrogenase; D001205:Ascorbic Acid