Acute, subchronic and chronic safety studies with genistein in rats

McClain, R.M.; Wolz, E.; Davidovich, A.; Pfannkuch, F; Edwards, John S.; Bausch, Jochen

doi:10.1016/j.fct.2005.05.021

Cited by 121 publications

(56 citation statements)

References 28 publications

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“…Genistein may has minimal uterotrophic effect by preferentially binding to ER since the main ER subtype in the uterus is ER [63], which may primarily mediate the uterotrophic effect of estrogen. Indeed, although genistein has been shown to affect development of the reproductive system and immune functions in experimental animals [64], but no such an effect has been reported in infants fed infant formula containing this compound or in various mature animal species fed pharmacological doses of genistein [16,[65][66][67][68][69]. Indeed, the dose of genistein required to produce an effect on uterus of mice is 10,000-fold higher than that of E2 [69].…”

Section: Genistein Is a Selective Er-ligandmentioning

confidence: 89%

Phytochemical Genistein in the Regulation of Vascular Function: New Insights

Liu²

2007

CMC

105

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Genistein, a natural bioactive compound derived from legumes, has drawn wide attention during the last decade because of its potentially beneficial effects on some human degenerative diseases. It has a weak estrogenic effect and is a well-known non-specific tyrosine kinase inhibitor at pharmacological doses. Epidemiological studies show that genistein intake is inversely associated with the risk of cardiovascular diseases. Data from animal and in vitro studies suggest a protective role of genistein in cardiovascular events. However, the mechanisms of the genistein action on vascular protective effects are unclear. Past extensive studies exploring its hypolipidemic effect resulted in contradictory data. Genistein also is a relatively poor antioxidant. However, genistein protects against pro-inflammatory factor-induced vascular endothelial barrier dysfunction and inhibits leukocyte-endothelium interaction, thereby modulating vascular inflammation, a major event in the pathogenesis of atherosclerosis. Recent studies found that genistein exerts a novel non-genomic action by targeting on important signaling molecules in vascular endothelial cells (ECs). Genistein rapidly activates endothelial nitric oxide synthase and production of nitric oxide in ECs. This genistein effect is novel since it is independent of its known effects, but mediated by the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) cascade. Further studies demonstrated that genistein directly stimulates the plasma membrane-associated adenylate cyclases, leading to activation of the cAMP signaling pathway. In addition, genistein activates peroxisome proliferator-activated receptors, ligand-activated nuclear receptors important to normal vascular function. Furthermore, genistein reduces reactive oxygen species (ROS) by attenuating the expression of ROS-producing enzymes. These new findings reveal the novel roles for genistein in the regulation of vascular function and provide a basis for further investigating its therapeutic potential for inflammatory-related vascular disease.

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Section: Genistein Is a Selective Er-ligandmentioning

confidence: 89%

Phytochemical Genistein in the Regulation of Vascular Function: New Insights

Liu²

2007

CMC

105

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“…The amount of food consumed by the mice was monitored and the approximate dose of genistein consumed was in the range of 80 mg/kg per day (each mouse consumed 2.03 mg/day per 25 g) which has been reported to give a plasma level in the range of 1-2 μmol/L [149]. Studies in rats of plasma values of genistein given a dose of 50 mg/kg/day gave values of about 11 μmol/L [177], which are significantly higher than the values reported for mice on the diet that we used. However, the technique of genistein measurement and the administration methods are different so it is difficult make a direct comparison.…”

Section: Control Dietmentioning

confidence: 99%

Effects of genistein following fractionated lung irradiation in mice

Para¹,

Bezjak²,

Yeung³

et al. 2009

Radiotherapy and Oncology

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Radiation therapy for lung cancer and cancers of the upper thorax is limited by side effects to normal tissue of the lung. An understanding of mechanisms leading to radiation induced lung damage is essential to developing protective agents. In this thesis an anti-oxidant and anti-inflammatory agent Genistein was investigated for its potential to affect DNA damage, tissue inflammation, functional deficits and survival. We hypothesized that chronic oxidative stress and the subsequent inflammatory response play a key role in the development of major lung complications, radiation pneumonitis and fibrosis. If side effects of radiation could be reduced, then larger doses could be delivered to the tumor with a better chance of eradicating the disease.ii Acknowledgements

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“…The doses of DEHP and genistein were chosen on the basis of previous reports (Shirota et al, 2005;Michael et al, 2006); we expected that the selected doses of DEHP 250 mg/kg/ day would produce small but not signifi cant changes, if any, on endpoints such as testicular testosterone level decrease or anogenital distance decrease, therefore any potentially cumulative effects would be better manifested. Serum concentration of phytoestrogen under a classical Asian diet is equivalent to that of a rat at the dose of 40-50 mg/kg (H et al, 1993;KS et al, 2001) and the no observed adverse eff ect level (NOAEL) of genistein is considered to be 50 mg/kg/ day (Michael et al, 2006).…”

Section: Chemicals and F0 Treatmentmentioning

confidence: 99%

“…Serum concentration of phytoestrogen under a classical Asian diet is equivalent to that of a rat at the dose of 40-50 mg/kg (H et al, 1993;KS et al, 2001) and the no observed adverse eff ect level (NOAEL) of genistein is considered to be 50 mg/kg/ day (Michael et al, 2006). No treatment-related teratogenic eff ects were noted in body weight, normalized anogenital distance, serum testosterone or sperm concentration in the male offspring after exposure to GEN 300 mg /kg bw/ day (Wisniewski et al, 2005) and GEN 500 mg /kg bw/day (McClain et al, 2007) during pregnancy.…”

Section: Chemicals and F0 Treatmentmentioning

confidence: 99%

Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl) phthalate and genistein

et al. 2013

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Studies of developmental eff ects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive eff ects of the co-administration of di-2-(ethylhexyl) phthalate (DEHP) and genistein (GEN) during pregnancy and lactation were studied in male rat off spring. Pregnant Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with vehicle control, DEHP 250 mg⁄kg body weight (bw)⁄day, GEN 50 mg⁄kg bw⁄day, GEN 400 mg⁄kg bw⁄day, and two combinations of the two compounds (DEHP 250 mg⁄kg bw⁄day + GEN 50 mg⁄kg bw⁄day, DEHP 250 mg⁄kg bw⁄day + GEN 400 mg⁄kg bw⁄day). The outcomes studied were general morphometry (weight, AGD), testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coeffi cient, AGD / body weight 1 / 3 , serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bw⁄day), GEN(50mg/kg bw⁄day) or GEN(400mg/kg bw⁄day) alone were not signifi cantly diff erent from the control group. When exposed to (DEHP 250mg/kg bw⁄day +GEN 50mg/kg bw⁄day) together during pregnancy and lactation, serum testosterone concentration, epididymis coeffi cient and Cypal17a1,Scarb1 m RNA expression signifi cantly decreased compared to the control and GEN(50mg/kg bw⁄day). When exposed to (DEHP 250mg/kg bw⁄day +GEN 400mg/kg bw⁄day) together during pregnancy and lactation, AGD / body weight 1 / 3 , serum testosterone concentration, testis and epididymis coeffi cient and Star, Cypal17a1 mRNA expression appeared signifi cantly decreased compared to the control and DEHP/GEN single exposure, together with developmental impairment of seminiferous tubules and seminiferous epithelium. Overall, co-administration of DEHP and GEN during gestation and lactation seem to acts in a cumulative manner to induce the most signifi cant alterations in the neonate, especially with GEN at high dose, although the eff ect of the DEHP-GEN mixture on adult off spring should be observed further.

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Acute, subchronic and chronic safety studies with genistein in rats

Cited by 121 publications

References 28 publications

Phytochemical Genistein in the Regulation of Vascular Function: New Insights

Phytochemical Genistein in the Regulation of Vascular Function: New Insights

Effects of genistein following fractionated lung irradiation in mice

Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl) phthalate and genistein

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