A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics

(2003). Hepatotoxicity and Mechanism of Action of Haloalkanes: Carbon Tetrachloride as a Toxicological Model. Critical Reviews in Toxicology: Vol. 33, No. 2, pp. 105-136.

Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model.

This review is focused on purinergic neurotransmission, i.e., ATP released from nerves as a transmitter or cotransmitter to act as an extracellular signaling molecule on both pre- and postjunctional membranes at neuroeffector junctions and synapses, as well as acting as a trophic factor during development and regeneration. Emphasis is placed on the physiology and pathophysiology of ATP, but extracellular roles of its breakdown product, adenosine, are also considered because of their intimate interactions. The early history of the involvement of ATP in autonomic and skeletal neuromuscular transmission and in activities in the central nervous system and ganglia is reviewed. Brief background information is given about the identification of receptor subtypes for purines and pyrimidines and about ATP storage, release, and ectoenzymatic breakdown. Evidence that ATP is a cotransmitter in most, if not all, peripheral and central neurons is presented, as well as full accounts of neurotransmission and neuromodulation in autonomic and sensory ganglia and in the brain and spinal cord. There is coverage of neuron-glia interactions and of purinergic neuroeffector transmission to nonmuscular cells. To establish the primitive and widespread nature of purinergic neurotransmission, both the ontogeny and phylogeny of purinergic signaling are considered. Finally, the pathophysiology of purinergic neurotransmission in both peripheral and central nervous systems is reviewed, and speculations are made about future developments.

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Physiology and Pathophysiology of Purinergic Neurotransmission

Human serum albumin: from bench to bedside.

Equol [7-hydroxy-3-(4'-hydroxyphenyl)-chroman] is a nonsteroidal estrogen of the isoflavone class. It is exclusively a product of intestinal bacterial metabolism of dietary isoflavones and it possesses estrogenic activity, having affinity for both estrogen receptors, ERalpha and ERbeta. Equol is superior to all other isoflavones in its antioxidant activity. It is the end product of the biotransformation of the phytoestrogen daidzein, one of the two main isoflavones found in abundance in soybeans and most soy foods. Once formed, it is relatively stable; however, equol is not produced in all healthy adults in response to dietary challenge with soy or daidzein. Several recent dietary intervention studies examining the health effects of soy isoflavones allude to the potential importance of equol by establishing that maximal clinical responses to soy protein diets are observed in people who are good "equol-producers." It is now apparent that there are two distinct subpopulations of people and that "bacterio-typing" individuals for their ability to make equol may hold the clue to the effectiveness of soy protein diets in the treatment or prevention of hormone-dependent conditions. In reviewing the history of equol, its biological properties, factors influencing its formation and clinical data, we propose a new paradigm. The clinical effectiveness of soy protein in cardiovascular, bone and menopausal health may be a function of the ability to biotransform soy isoflavones to the more potent estrogenic isoflavone, equol. The failure to distinguish those subjects who are "equol-producers" from "nonequol producers" in previous clinical studies could plausibly explain the variance in reported data on the health benefits of soy.

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The Clinical Importance of the Metabolite Equol—A Clue to the Effectiveness of Soy and Its Isoflavones

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2891%2980168-3

Inhibitory effect of calcium-binding protein regucalcin on Ca2(+)-activated DNA fragmentation in rat liver nuclei.

Inhibitory effect of genistein on osteoclast-like cell formation in mouse marrow cultures.

Changes in circulating vitamin K2 (menaquinone-7, MK-7) and gamma-carboxylated osteocalcin concentrations in normal individuals with the intake of fermented soybeans (natto) were investigated. Eight male volunteers were given sequentially fermented soybeans (natto) containing three different contents of MK-7 at an interval of 7 days as follows: regular natto including 775 micrograms/100 g (MK-7 x 1) or reinforced natto containing 1298 micrograms/100 g (MK-7 x 1.5) or 1765 micrograms/100 g (MK-7 x 2). Subsequently, it was found that serum MK-7 and gamma-carboxylated osteocalcin concentrations were significantly elevated following the start of dietary intake of MK-7 (1298 or 1765 micrograms/100 g). Serum undercarboxylated osteocalcin concentrations were significantly decreased by dietary MK-7 (1765 micrograms/100 g) supplementation. Moreover, the changes in serum MK-7 level with the frequency of dietary natto intake were examined in 134 healthy adults (85 men and 39 women) without and with occasional (a few times per month), and frequent (a few times per week) dietary intake of regular natto including MK-7 (775 micrograms/100 g). Serum MK-7 and gamma-carboxylated osteocalcin concentrations in men with the occasional or frequent dietary intake of natto were significantly higher than those without any intake. The present study suggests that intake of fermented soybean (natto) increases serum levels of MK-7 and gamma-carboxylated osteocalcin in normal individuals.

Intake of fermented soybean (natto) increases circulating vitamin K2 (menaquinone-7) and gamma-carboxylated osteocalcin concentration in normal individuals.

Bone loss with increasing age induces osteoporosis. This loss may be due to increased bone resorption and decreased bone formation. Osteoporosis with a decrease in bone mass is widely recognized as a major public health problem. Pharmacological and nutritional factors may prevent bone loss with increasing age. The chemical compounds in food that act on bone metabolism, however, are poorly understood. Genistein is a natural isoflavonoid phytoestrogen found in Leguminosae and has been demonstrated to have an anabolic effect on bone metabolism, suggesting its role in the prevention of osteoporosis. Genistein has a stimulatory effect on bone formation and mineralization in the tissue culture system in vitro, and it can stimulate protein synthesis in osteoblastic cells. Moreover, genistein has been shown to inhibit osteoblastic bone resorption by preventing the formation and differentiation of osteoclast-like cells from bone marrow cells, and the apoptosis of mature osteoclasts is induced by genistein through the Ca2+ signaling mechanism. Also, the suppressive effect of genistein on rat bone osteoclasts is partly involved in the inhibition of protein kinase and the activation of protein tyrosine phosphatase in osteoclasts. Daidzein, an isoflavone, did not have a greater effect than genistein. Various polyphenols [glycitein, resveratol, quercetin, catechin, and (-)-epigallocatechin gallate] found in food and plants did not have an anabolic effect on bone calcification in tissue culture in vitro. Genistein may be of significance in the prevention of bone loss with increasing age. The dietary intake of isoflavone (genistein and daidzein) could prevent bone loss in ovariectomized rats which are model animals of osteoporosis. In addition, the preventive effect of genistein on bone loss with aging is enhanced by the combination of zinc or casein phosphopeptides as food factors. Genistein is a useful biofactor in the prevention of osteoporosis.

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Isoflavone and Bone Metabolism : Its Cellular Mechanism and Preventive Role in Bone Loss

The effect of zinc sulfate on the mRNA expressions in Runx2, osteocalcin, α1(I) collagen, insulin-like growth factor-I (IGF-I), transforming growth factor-β1 (TGF-β1), osteoprotegerin (OPG), regucalcin, zinc transporter 1 (ZIP1), or glyceroaldehyde-3-phosphate dehydrogenase (G3PDH) in osteoblastic MC3T3-E1 cells in vitro was investigated. Cells with subconfluency were cultured for 48 h in a medium containing either vehicle or zinc sulfate (10−6–10−4 M) without fetal bovine serum. Culture with zinc sulfate (10−5 M) caused a significant increase in Runx2, OPG, or regucalcin mRNA expressions in the cells, while it did not have a significant effect on osteocalcin, α1(I) collagen, IGF-I, TGF-β1, ZIP1, or G3PDH mRNA expressions. The effect of zinc sulfate (10−4 M) in increasing Runx2 mRNA expression was seen at 24–72 h after culture. A significant increase in OPG mRNA expression was observed at 24 or 48 h after culture. Regucalcin mRNA expression was significantly increased at 48 or 72 h after culture with zinc sulfate (10−4 M). The stimulatory effects of zinc sulfate on Runx2, OPG, or regucalcin mRNAs were significantly prevented in the presence of cycloheximide (10−7 M), an inhibitor of protein synthesis, or 5,6-dichloro-1-β-d-ribofuranosyl-benzimidazole (10−6 M), an inhibitor of transcription activity. Culture with β-alanyl-l-histidinato zinc (10−5 M) caused a significant increase in Runx2 or regucalcin mRNA expressions, while zinc acexamate (10−5 M) did not have a significant effect on Runx2, OPG, ZIP1, or regucalcin mRNA expressions. This study demonstrates that zinc sulfate has a role in the enhancement of Runx2, OPG, or regucalcin mRNA expression in osteoblastic cells in vitro, suggesting its role in the regulation of gene expression in the cells.

Masayoshi Yamaguchi

Papers

Inhibitory effect of calcium-binding protein regucalcin on Ca2(+)-activated DNA fragmentation in rat liver nuclei.

Inhibitory effect of genistein on osteoclast-like cell formation in mouse marrow cultures.

Intake of fermented soybean (natto) increases circulating vitamin K2 (menaquinone-7) and gamma-carboxylated osteocalcin concentration in normal individuals.

Isoflavone and Bone Metabolism : Its Cellular Mechanism and Preventive Role in Bone Loss

Effect of zinc on gene expression in osteoblastic MC3T3-E1 cells: enhancement of Runx2, OPG, and regucalcin mRNA expressions.