Tumor suppression effects of bilberry extracts and enzymatically modified isoquercitrin in early preneoplastic liver cell lesions induced by piperonyl butoxide promotion in a two-stage rat hepatocarcinogenesis model

Hara, Shintaro; Morita, Rimpei; Ogawa, Takashi; Segawa, Risa; Takimoto, Norifumi; Suzuki, Kazuhiko; Hamadate, Naobumi; Hayashi, Shim-mo; Odachi, Ayano; Ogiwara, Isao; Shibusawa, Sakae; Yoshida, Toshinori; Shibutani, Makoto

doi:10.1016/j.etp.2014.02.002

Cited by 25 publications

(27 citation statements)

References 40 publications

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“…An avidin-biotin-peroxidase complex method with VECTASTAIN® Elite ABC kit (Vector Laboratories Inc., Burlingame, CA, USA) was employed with 3,3'-diaminobenzidine as a chromogen, followed by light hematoxylin staining. The numbers and areas of GST-P-positive foci (> 0.2-mm diameter) and the total areas of the liver sections were quantified using Scion Image (Scion Corp., Frederick, MD, USA) (Hara et al, 2014). Ki-67-and active-caspase-3-positive cells were examined in a total of more than 1,000 cells within GST-P-positive foci (inside foci) per animal.…”

Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

Differential impacts of mineralocorticoid receptor antagonist potassium canrenoate on liver and renal changes in high fat diet-mediated early hepatocarcinogenesis model rats

et al. 2018

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Mineralocorticoid receptor (MR)/NADPH oxidase (NOX) signaling is involved in the development of obesity, insulin resistance, and renal diseases; however, the role of this signaling on steatotic preneoplastic liver lesions is not fully elucidated. We determined the effects of the MR antagonist potassium canrenoate (PC) on MR/NOX signaling in hepatic steatosis and preneoplastic glutathione S-transferase placental form (GST-P)-positive liver foci. Rats were subjected to a two-stage hepatocarcinogenesis model and fed with basal diet or high fat diet (HFD) that was co-administered with PC alone or in combination with the antioxidant alpha-glycosyl isoquercitrin (AGIQ). PC reduced obesity and renal changes (basophilic tubules that expressed MR and p22phox) but did not affect blood glucose tolerance and non-alcoholic fatty liver disease activity score (NAS) in HFD-fed rats. However, the drug increased the area of GST-P-positive liver foci that expressed MR and p22phox as well as increased expression of NOX genes (p22phox, Poldip2, and NOX4). PC in combination with AGIQ had the potential of inhibiting the effects of PC on the area of GST-P-positive liver foci and the effects were associated with increasing expression of an anti-oxidative enzyme (Catalase). The results suggested that MR/NOX signaling might be involved in development of preneoplastic liver foci and renal basophilic changes in HFD-fed rats; however, the impacts of PC were different in each organ.

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Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

Differential impacts of mineralocorticoid receptor antagonist potassium canrenoate on liver and renal changes in high fat diet-mediated early hepatocarcinogenesis model rats

et al. 2018

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“…However, this promotion was suppressed by cotreatment with bilberry extracts and IQ, which Orfali GC et al . Isoquercitrin in cancer suppressed the proliferation activity of preneoplastic liver cells [93] .…”

Section: Liver Cancermentioning

confidence: 99%

Review of anticancer mechanisms of isoquercitin

Orfali¹,

Duarte²,

Bonadio³

et al. 2016

WJCO

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This review was based on a literature search of PubMed and Scielo databases using the keywords "quercetin, rutin, isoquercitrin, isoquercitin (IQ), quercetin-3-glucoside, bioavailability, flavonols and favonoids, and cancer" and combinations of all the words. We collected relevant scientific publications from 1990 to 2015 about the absorption, bioavailability, chemoprevention activity, and treatment effects as well as the underlying anticancer mechanisms of isoquercitin. Flavonoids are a group of polyphenolic compounds widely distributed throughout the plant kingdom. The subclass of flavonols receives special attention owing to their health benefits. The main components of this class are quercetin, rutin, and IQ, which is a flavonoid and although mostly found as a glycoside, is an aglycone (lacks a glycoside side chain). This compound presents similar therapeutic profiles to quercetin but with superior bioavailability, resulting in increased efficacy compared to the aglycone form. IQ has therapeutic applications owing to its wide range of pharmacological effects including antioxidant, antiproliferative, anti-inflammatory, anti-hypertensive, and anti-diabetic. The protective effects of IQ in cancer may be due to actions on lipid peroxidation. In addition, the antitumor effect of IQ and its underlying mechanism are related to interactions with Wnt signaling pathway, mixed-lineage protein kinase 3, mitogen-activated protein kinase, apoptotic pathways, as well proinflammatory protein signaling. This review contributed to clarifying the mechanisms of absorption, metabolism, and actions of IQ and isoquercitrin in cancer.

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“…In the present study, mean postweaning exposure level of exogenously administered AGIQ or ALA in PTU-exposed offspring was 516.1 and 103.4 mg/kg body weight/ day, respectively. While antioxidant effect of AGIQ has not been reported in the brain injury model until now, 5,000 ppm dietary dose of AGIQ has shown to suppress hepatocellular tumor promotion in rats (Fujii et al, 2013a;Hara et al, 2014;Kuwata et al, 2011). These Table 2.…”

Section: Discussionmentioning

confidence: 97%

“…Both AGIQ and ALA were powdered compound and mixed with powdered basal diet to the determined concentration. The chosen dosage of AGIQ or ALA has been shown to suppress the promotion of hepatic preneoplastic lesions in rats (Fujii et al, 2013a(Fujii et al, , 2013bHara et al, 2014;Kuwata et al, 2011). All dams of PTU-exposed group were euthanized on PND 28.…”

Section: Experimental Designmentioning

confidence: 99%

Ameliorating effect of postweaning exposure to antioxidant on disruption of hippocampal neurogenesis induced by developmental hypothyroidism in rats

et al. 2019

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Developmental hypothyroidism as a model of autism spectrum disorders disrupts hippocampal neurogenesis through the adult stage. The present study investigated the ameliorating effect of postweaning exposure to antioxidant on the hypothyroidism-induced disruptive neurogenesis. Mated female Sprague-Dawley rats were treated with 0 or 10 ppm 6-propyl-2-thiouracil (PTU) as an anti-thyroid agent in drinking water from gestational day 6 to postnatal day (PND) 21 on weaning. PTU-exposed male offspring were fed either basal diet, diet containing α-glycosyl isoquercitrin (AGIQ) at 5,000 ppm or α-lipoic acid (ALA) at 1,000 ppm as an antioxidant from PND 21 to PND 77. PTU-exposure decreased DCX + and NeuN + granule cell lineage subpopulations, synaptic plasticity-related FOS + granule cells, and hilar PVALB + and GAD67 + GABAergic interneurons, increased hilar SST + and CALB2 + interneurons, and upregulated Gria3, Otx2, and antioxidant enzyme genes in the dentate gyrus on PND 77. These results suggest disruption of neurogenesis remained in relation with increase of oxidative stress and compensatory responses to the disruption at the adult stage. AGIQ recovered expression of some antioxidant enzyme genes and was effective for restoration of NeuN + postmitotic granule cells and PVALB + and SST + interneurons. In contrast, ALA was effective for restoration of all interneuron subpopulations, as well as postmitotic granule cells, and upregulated Grin2a that may play a role for the restoration. Both antioxidants recovered expression of Otx2 and AGIQ-alone recovered Gria3, suggesting a reversal of disruptive neurogenesis by compensatory responses. Thus, postweaning antioxidant exposure may be effective for ameliorating developmental hypothyroidism-induced disruptive neurogenesis by restoring the function of regulatory system.

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Tumor suppression effects of bilberry extracts and enzymatically modified isoquercitrin in early preneoplastic liver cell lesions induced by piperonyl butoxide promotion in a two-stage rat hepatocarcinogenesis model

Cited by 25 publications

References 40 publications

Differential impacts of mineralocorticoid receptor antagonist potassium canrenoate on liver and renal changes in high fat diet-mediated early hepatocarcinogenesis model rats

Differential impacts of mineralocorticoid receptor antagonist potassium canrenoate on liver and renal changes in high fat diet-mediated early hepatocarcinogenesis model rats

Review of anticancer mechanisms of isoquercitin

Ameliorating effect of postweaning exposure to antioxidant on disruption of hippocampal neurogenesis induced by developmental hypothyroidism in rats

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