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Biomedical subjects

N I Krinsky

Publications and source records attributed to N I Krinsky.

At least 73 records · Page 4Linked to original sources
PubMed1991

Effects of carotenoids in cellular and animal systems.

It has been suggested that carotenoid pigments may function as chemopreventive agents for reducing the risk of cancer in humans. Part of this suggestion rests on epidemiological evidence, and part rests on work done in cellular and animal systems. In this article, the experimental evidence for carotenoid inhibition of mutagenicity, malignant transformation, tumor formation, and immunoenhancement is reviewed. Although a mechanism for these effects cannot yet be identified, it is clear that the overwhelming evidence in these systems would indicate that carotenoids exert an important influence in modulating the actions of carcinogens.

Animals↗
PubMed1991

Effects of carotenoid administration on bladder cancer prevention.

Bladder cancer was induced in male B6D2F1 strain mice by the administration of N-butyl-N-(4-hydroxybutyl)nitrosamine. Mice supplemented with beta-carotene for 5 weeks before receiving the carcinogen and maintained on beta-carotene for an additional 26 weeks developed significantly fewer tumors than did unsupplemented mice. Mice receiving canthaxanthin for the same time period showed no protection against the development of bladder cancer.

Animals↗
PubMed1991

Biological control of primate macular pigment. Biochemical and densitometric studies.

The amounts of zeaxanthin (Z) and lutein (L), the carotenoids constituting the primate macular pigment, were measured in the central retinas of monkeys (Saimiri sciureus and Macaca fascicularis). Two independent methods--reverse-phase high-performance liquid chromatography (HPLC) and microdensitometry--were used for analysis of the same set of retinas. Most of the measurements were made on retinas that had been fixed by glutaraldehyde-paraformaldehyde perfusion of the animal. Control experiments showed that this fixation did not interfere with the quantitative extraction and analysis of the carotenoids. The amount of macular pigment calculated from microdensitometry of the foveal region was proportional to the amount of pigment assayed by HPLC of the same retinal area, demonstrating that either method can be used reliably to rank the carotenoid content of aldehyde-fixed foveas. The optical density of pigment in the axial direction through the retina was higher than would be predicted if the pigment were randomly oriented. This is consistent with the idea that the nonrandom orientation of the dichroic macular pigment molecules found in previous studies contributes to increased optical filtering of the retinal image. Comparisons of the amounts of Z and L between the left and right eyes of the same monkey, within 1 mm of the foveal center, always showed excellent agreement (averaging a 5% difference for Z and 11% difference for L), whereas differences among individual monkeys were very large (up to fourfold for Z). These results indicate that the uptake and assimilation of the macular carotenoids are biologically regulated by selective mechanisms in primate retinas.

Animals↗
PubMed1990

The metabolism of [14C]beta-carotene and the presence of other carotenoids in rats and monkeys.

The metabolism of beta-carotene has been studied in both rats and Rhesus monkeys, following the oral administration of [14C]beta-carotene in olive oil supplemented with 1 mg/mL alpha-tocopherol. In the rats, peak serum accumulation of [14C]retinol occurred 4 h after a single oral dose, but we were not able to detect [14C]beta-carotene in rat sera at any time up to 72 h after dosing. Small amounts of [14C]beta-carotene were found in the livers, although 88-94% of the recovered radioactivity was localized in the retinol fraction after saponification. Although radioactivity was also found in fractions other than beta-carotene and retinol, the amounts were too small to allow characterization. In the monkeys, peak accumulation of [14C]retinol in serum occurred between 8 and 24 h after supplementation. Some [14C]beta-carotene was also present. Most of the absorbed radioactivity was stored in the liver as [14C]retinol, although 2-8% was present as [14C]beta-carotene. Other organs also contained [14C]beta-carotene, confirming the ability of the monkey to absorb intact beta-carotene. In addition, monkey livers and other organs were found to contain lutein, zeaxanthin, alpha-cryptoxanthin, beta-cryptoxanthin and beta-carotene, presumably arising from dietary sources.

Absorption↗
PubMed1990

Distribution of [14C]canthaxanthin and [14C]lycopene in rats and monkeys.

The absorption and distribution of [14C]-canthaxanthin and [14C]lycopene were studied in rats and in rhesus monkeys following the oral administration of [14C]canthaxanthin or [14C]lycopene in olive oil supplemented with 1 mg alpha-tocopherol/mL. For canthaxanthin and lycopene, peak accumulation of radioactivity in plasma occurred between 4 and 8 h in rats and between 8 and 48 h in monkeys. In rats, the liver contained the largest amount of both kinds of radioactive pigments. In monkeys, with the exception of one stomach sample, liver was also the major depot organ for both canthaxanthin and lycopene. The other organs tested accumulated various amounts of pigment. No labeled metabolic products of either canthaxanthin or lycopene were found.

Administration, Oral↗
PubMed1990

Structural and geometrical isomers of carotenoids in human plasma.

We have quantitatively analyzed human plasma for the following carotenoids: all-trans-lutein, all-trans-zeaxanthin, alpha-cryptoxanthin, beta-cryptoxanthin, the sum of all-trans-lycopene and its cis isomers, alpha-carotene and beta-carotene. In addition, we have tentatively identified and quantified 13-cis-lutein and 13-cis-zeaxanthin in human plasma. The latter two cis isomers are also apparent in samples of two common food items, spinach and corn meal. We have analyzed the ratios of all of the members of the beta, beta family of carotenoids (zeaxanthin, beta-cryptoxanthin and beta-carotene) to their corresponding beta, epsilon structural isomers (lutein, alpha-cryptoxanthin and alpha-carotene) in human plasma. There are marked differences in these ratios, with beta-carotene and beta-cryptoxanthin predominating in the carotene and monohydroxy-xanthophyll classes and lutein predominating in the dihydroxy-xanthophyll class. These differences could be attributable to dietary intake or to specific mechanisms in the way humans absorb and utilize these compounds.

Adult↗
PubMed1990

Plasma carotenoids of monkeys (Macaca fascicularis and Saimiri sciureus) fed a nonpurified diet.

The major carotenoid pigments in the plasma and in a common, nonpurified diet of two species of monkeys (Macaca fascicularis and Saimiri sciureus) were measured. The xanthophylls, lutein, zeaxanthin, alpha-cryptoxanthin, and beta-cryptoxanthin, were the principal carotenoids in both the diet and the plasma. Lutein and zeaxanthin were abundant in the all-trans, the 9-cis, and the 13-cis geometrical isomers in the diet, but the 9-cis form was rarely measurable in plasma. However, the 13-cis isomers of lutein and zeaxanthin were found in higher proportions in plasma than in the diet. For both the monohydroxy-xanthophylls, alpha-cryptoxanthin and beta-cryptoxanthin, and the dihydroxy-xanthophylls, lutein and zeaxanthin, the beta, beta structural isomer (beta-cryptoxanthin or zeaxanthin) is less abundant than the beta, epsilon isomer in plasma than in the diet. These results indicate substantial specificity in the absorption or retention of closely related carotenoid isomers in primates. The proportions of different geometrical isomers of lutein and zeaxanthin in the plasma of both species of monkeys were nearly identical and were similar to human values. The hydrocarbon carotenoids, alpha-carotene, beta-carotene and lycopene were usually undetectable in monkey plasma. The monkeys appear to be like humans in their utilization of lutein and zeaxanthin but distinctly different in some other aspects of carotenoid utilization.

Animal Feed↗
PubMed1989

Carotenoids as chemopreventive agents.

Carotenoid pigments have been suggested as chemopreventive agents for reducing cancer risk in humans. In this article, the functions of carotenoids are reviewed, and the experimental evidence for carotenoid inhibition of mutagenicity, malignant transformation, and tumor formation is reviewed. It is suggested that the antioxidant function of carotenoids may explain their divergent effects as chemopreventive agents.

Animals↗
PubMed1989

Antioxidant functions of carotenoids.

Carotenoid pigments, including hydrocarbons such as beta-carotene or xanthophylls such as lutein and zeaxanthin, are very widely distributed in nature, where they play an important role in protecting cells and organisms against the harmful effects of light, air, and sensitizer pigments. This process has been demonstrated in bacteria, algae, plants, animals, and even in humans in the light-sensitive disease, erythropoietic protoporphyria. The primary mechanism of action of this phenomenon appears to be the ability of carotenoids to quench excited sensitizer molecules as well as quench 1O2. In addition to this protection, and potentially of even greater biological importance, is the fact that carotenoids can also serve as antioxidants under conditions other than photosensitization. This review presents the data available indicating the extent of this important function. Antioxidant action can be documented in both enzymic and nonenzymic systems, and has been reported in subcellular, cellular, and animal studies. In fact, the many reports indicating that carotenoids may possess some anticarcinogenic properties may well be related to their ability to interact with and quench various radical species that can be generated within cells.

Animals↗
PubMed1989

Carotenoids and cancer in animal models.

As evidence accumulated from epidemiological studies that beta-carotene acts as a chemopreventive agent with respect to inhibiting the appearance of certain types of tumors in humans, attention focused on animal models as a means of extending our understanding of carotenoid function. Unfortunately, most animals used in research are "white fat" animals, and require large amounts of carotenoids in their diets to obtain significant blood and tissue levels. Even with these limitations, beta-carotene, a provitamin A carotenoid, as well as canthaxanthin, a non-provitamin A carotenoid, have been shown to protect animals against UV-induced skin tumors, UV and carcinogen-induced tumors, and carcinogen treatment alone. Similar observations have been made in cell and organ cultures where carotenoids have been shown to prevent malignant transformation and nuclear damage. Although the mechanism of this protection is still unclear, the evidence continues to accumulate that carotenoids may possess intrinsic chemopreventive action with respect to tumor formation.

Animals↗
PubMed1988

Membrane antioxidants.

In this chapter, I have discussed both lipid-soluble and water-soluble antioxidants that exert protective action with respect to inhibiting lipid, and in some cases, protein oxidation in both natural and artificial membranes. In addition, recent work has begun to clarify exactly how antioxidant enzymes can protect membranes against peroxidative damage. Although we have some understanding of the mechanisms of several of these antioxidants, much work remains to be done before we can begin making dietary recommendations that may have profound implications with respect to aging, cancer, and the many other human diseases that have been associated with radical-induced damage.

Animals↗
PubMed1987

Comparison of the inactivation of Bacillus subtilis transforming DNA by the potassium superoxide and xanthine-xanthine oxidase systems for generating superoxide.

Potassium superoxide (KO2) and xanthine-xanthine oxidase (X-XO), which are known generating systems for the superoxide anion, have different inactivating actions on Bacillus subtilis transforming DNA in vitro. Superoxide dismutase and CuSO4 enhanced the inactivation for KO2, but not for X-XO. Mannitol, a hydroxyl radical scavenger, protected against the inactivation by X-XO, but not by KO2. The results obtained with X-XO were consistent with the involvement of Fenton reactions, in which hydroxyl radical is the reactive species that ultimately causes damage. On the other hand, KO2-induced inactivation was partly due to the effect of H2O2. Differences in inactivation between the KO2 and X-XO systems may result from the different rates of production of the superoxide anion.

Bacillus subtilis↗
PubMed1985

Superoxide anion is generated from cellular metabolites by solar radiation and its components.

Several endogenous cellular constituents were tested for their ability to produce superoxide anion (O2-) from ground-state molecular oxygen upon irradiation by solar radiation. The pyridine cofactors NADPH and NADH, riboflavin, and the nucleosides 2-thiouracil and 4-thiouridine were found to sensitize the transmission of photon energy from solar radiation and monochromatic radiation (290, 334, 365, and 405 nm) to oxygen, resulting in O2- formation, as detected by superoxide dismutase-inhibitable cytochrome c reduction. Quantum yields for the production of O2- indicate that NADPH is the most efficient and riboflavin the least efficient of the compounds tested. These data indicate that endogenous compounds may participate in the production of O2- by solar radiation and imply that O2- may play a role in sunlight-induced erythema and dermal carcinogenesis.

Anions↗
PubMed1984

Comparison of myeloperoxidase and hemi-myeloperoxidase with respect to catalysis, regulation, and bactericidal activity.

It has been demonstrated previously (P.C. Andrews and N.I. Krinsky (1981) J. Biol. Chem. 256, 4211-4218) that human leukocyte myeloperoxidase, an alpha 2 beta 2 enzyme, can be cleaved by mild reduction and alkylation to an alpha 1 beta 1 structure that we have termed hemi-myeloperoxidase. The native enzyme and hemi-myeloperoxidase have the same specific activity in a Cl--independent peroxidase assay and identical visible spectra under either oxidized or reduced conditions. This paper compares other properties of native and hemi-myeloperoxidase. Both enzymes are inhibited by high concentrations of H2O2 in an identical fashion. Both enzymes showed identical regulation by pH and Cl-. The utilization of Cl-, as assayed by chlorination of diethanolamine, was moderately decreased in hemi-myeloperoxidase. This reduction in chlorination was not reflected in a bactericidal assay, where again, hemi-myeloperoxidase was identical in activity to native myeloperoxidase.

Benzidines↗