Spironolactone in Combination with α-glycosyl Isoquercitrin Prevents Steatosis-related Early Hepatocarcinogenesis in Rats through the Observed NADPH Oxidase Modulation
| Autor: | Toshinori Yoshida, Masahi Kawashima, Ryoichi Ohtsuka, Sayaka Mizukami, Ayumi Eguchi, Emi Makino, Rei Nagahara, Mihoko Koyanagi, Hirotada Murayama, Makoto Shibutani, Misato Nakamura, Masayuki Kimura, Robert R. Maronpot, Shim-mo Hayashi, Naofumi Takahashi |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Antioxidant medicine.medical_treatment Spironolactone Pharmacology Diet High-Fat Toxicology Pathology and Forensic Medicine 03 medical and health sciences chemistry.chemical_compound Liver Neoplasms Experimental medicine Animals Glycosyl Molecular Biology NADPH oxidase biology Chemistry Body Weight NADPH Oxidases High fat diet Organ Size Cell Biology medicine.disease Rats Inbred F344 Fatty Liver Oxidative Stress 030104 developmental biology biology.protein Drug Therapy Combination Quercetin Steatosis Diuretic Precancerous Conditions |
| Zdroj: | Toxicologic Pathology. 46:530-539 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/0192623318778508 |
| Popis: | Administration of the diuretic, spironolactone (SR), can inhibit chronic liver diseases. We determined the effects of SR alone or in combination with the antioxidant α-glycosyl isoquercitrin (AGIQ) on hyperlipidemia- and steatosis-related precancerous lesions in high-fat diet (HFD)-fed rats subjected to a two-stage hepatocarcinogenesis model. Rats were fed with control basal diet or HFD, which was administered with SR alone or in combination with an antioxidant AGIQ in drinking water. An HFD increased body weight, intra-abdominal fat (adipose) tissue weight, and plasma lipids, which were reduced by coadministration of SR and AGIQ. SR and AGIQ coadministration also reduced hepatic steatosis and preneoplastic glutathione S-transferase placental form-positive foci, in association with decrease in NADPH oxidase (NOX) subunit p22phox-positive cells and an increase in active-caspase-3-positive cells in the foci. Hepatic gene expression analysis revealed that the coadministration of SR and AGIQ altered mRNA levels of lipogenic enzymes ( Scd1 and Fasn), antioxidant-related enzymes ( Catalase), NOX component ( P67phox), and anti-inflammatory transcriptional factor ( Pparg). Our results indicated that SR in combination with AGIQ had the potential of suppressing hyperlipidemia- and steatosis-related early hepatocarcinogenesis through the reduced expression of NOX subunits. |
| Databáze: | OpenAIRE |
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