PubMed · 8990763
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W E Golden, N Sanchez, B Pitts. 1996. Pseudomembranous colitis.. https://pubmed.ncbi.nlm.nih.gov/8990763/
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Two experiments investigated the effects of Fe(2+), administered postnatally to rat pups on days 10-12, upon tests of memory performance and motor behaviour. In experiment I, Wistar rat pups were administered Fe(2+) at doses of either 2.5, 7.5, 15.0 or 30.0 mg/kg, or vehicle, postnatally, and tested in the open-field at 3 months of age, followed 6 weeks later by testing in the radial arm maze. In the open-field test, only the 30.0 mg/kg Fe(2+) group showed a significantly decreased number of ambulations, but not rearings. In the radial arm maze, all four dose groups, demonstrated deficits in acquisition performance from test days 3 to 5. Retention quotients confirmed the cognitive deficits over all four Fe(2+) groups. In experiment II, rats were administered either 2.5, 7.5 or 22.5 mg Fe(2+) per kg, or vehicle, postnatally, and tested in the inhibitory avoidance (IA) conditioning and retention test at 3 months of age. In the IA conditioning test, groups were either given five 10-min preexposures to the test chamber (preexposed) or simply moved to another cage (non-preexposed). IA retention was blocked in non-preexposed rats administered 7.5 and 22.5 mg Fe(2+) per kg whereas in preexposed rats the 7.5 mg/kg group did not differ from the control (vehicle) group, although the preexposed control group showed significantly better retention than the non-preexposed control group. Postnatal iron administration appears to induce long-lasting detrimental effects upon performance of both appetitively and negatively reinforced tests of memory. Analysis of iron content indicated significant increases in the substantia nigra of the 7.5, 15.0 and 30.0 mg/kg dose groups, but not in the 2.5 mg/kg dose group. Postnatal iron administration appears to induce far-reaching effects upon the performance of certain learned behaviours.
In a previous study, we showed that naturally occurring organosulfur compounds (OSCs) from garlic and onion modulated the activation of carcinogen via the alteration of cytochromes P450. The present study was undertaken to determine the incidence of the in vivo induction of phase II enzymes by individual OSCs on the genotoxicity of several carcinogens. Diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS), were administered by gavage (1mmol/kg) to male SPF Wistar rats for 4 consecutive days. The effects of treatments on phase II enzymes and on the genotoxicity of carcinogens were evaluated with hepatic cytosols and microsomes from OSCs-treated rats. DADS strongly increased all the phase II enzymes activities examined, i.e. total glutathione S-transferase (GST) activity, mu GST activity, quinone reductase (QR) activity and epoxide hydrolase (EH) activity. In addition, DADS strongly increased the protein level of rGSTP1. QR activity, total and mu GST activities were also increased by DAS and DPDS whereas DPS increased only mu GST activity and QR activity. To assess the repercussions of these inductions on the genotoxicity of carcinogens, the effects of cytosols or microsomes from OSCs-treated rats on the mutagenicity of (+)-anti-7beta,8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), styrene oxide (SO) and 4-nitroquinoline 1-oxide (4-NQO) were measured in the Ames test. DADS showed a very effective antimutagenic activity against BPDE, SO and 4-NQO. DAS reduced the mutagenicity of BPDE and SO. In contrast, DPS and DPDS showed little efficient antimutagenic activity since they only reduced the mutagenicity of BPDE and 4-NQO, respectively. Interestingly, DADS appeared to be as effective as ethoxyquin, a model inducer of phase II enzymes, in both inducing phase II enzymes and inhibiting the mutagenicity of carcinogens. This study demonstrated that the antimutagenic activities of OSCs against several ultimate carcinogens were closely related to their ability to induce phase II enzymes.
To evaluate the general suitability of the rat for the micronucleus assay, we conducted the assay in males of 14 different strains, 13 inbred (ACI, BN, BUF, COP, DRH, F344, IS, LEW, RCS, SHR, WAG, WKYO, WTC) and 1 outbred (SD), using cyclophosphamide as the test chemical. Cyclophosphamide at 0 (vehicle), 5, 10, or 20mg/kg per day was administered orally twice, 24h apart, to five rats per dosage group. Bone marrow and peripheral blood were collected 24h after the second treatment. All 14 strains showed a positive response to cyclophosphamide, with slight differences in sensitivity. We concluded that the rat is suitable for the micronucleus assay regardless of strain.