β-Naphthoflavone protects mice from aristolochic acid-I-induced acute kidney injury in a CYP1A dependent mechanism

Xiao, Ying; Xue, Xiang; Wu, Yuan; Xin, Guo Zheng; Qian, Yong; Xie, Tian; Gong, Li; Ren, Jin

doi:10.1038/aps.2009.156

Cited by 29 publications

(26 citation statements)

References 35 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this report, AAIa was not detected in renal microsomes (data not shown). Induction of CYP1A activity with 3-MC or ␤-naphthoflavone (Xiao et al, 2009) increases resistance to AAI-elicited nephrotoxicity. In this study, 3-MC treatment increased hepatic microsomal AAI demethylation activity in both control and CYP1A2-null mice.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cytochrome P450 1A2 Detoxicates Aristolochic Acid in the Mouse

Rosenquist¹,

Einolf²,

Dickman³

et al. 2010

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:Aristolochic acids (AAs) are plant-derived nephrotoxins and carcinogens responsible for chronic renal failure and associated urothelial cell cancers in several clinical syndromes known collectively as aristolochic acid nephropathy (AAN). Mice provide a useful model for study of AAN because the renal histopathology of AA-treated mice is strikingly similar to that of humans. AA is also a potent carcinogen in mice with a tissue spectrum somewhat different from that in humans. The toxic dose of AA in mice is higher than that in humans; this difference in susceptibility has been postulated to reflect differing rates of detoxication between the species. Recent studies in mice have shown that the hepatic cytochrome P450 system detoxicates AA, and inducers of the arylhydrocarbon response protect mice from the nephrotoxic effects of AA. The purpose of this study was to determine the role of specific cytochrome P450 (P450) enzymes in AA metabolism in vivo. Of 18 human P450 enzymes we surveyed only two, CYP1A1 and CYP1A2, which were effective in demethylating 8-methoxy-6-nitro-phenanthro- (3,4-d)-1,3-dioxolo-5-carboxylic acid (AAI) to the nontoxic derivative 8-hydroxy-6-nitro-phenanthro-(3,4-d)-1,3-dioxolo-5-carboxylic acid (AAIa). Kinetic analysis revealed similar efficiencies of formation of AAIa by human and rat CYP1A2. We also report here that CYP1A2-deficient mice display increased sensitivity to the nephrotoxic effects of AAI. Furthermore, Cyp1a2 knockout mice accumulate AAI-derived DNA adducts in the kidney at a higher rate than control mice. Differences in bioavailability or hepatic metabolism of AAI, expression of CYP1A2, or efficiency of a competing nitroreduction pathway in vivo may explain the apparent differences between human and rodent sensitivity to AAI.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Conversely, pretreatment of mice with 3-methylcholanthrene or ␤-naphthoflavone (Xiao et al, 2009), agonists of the arylhydrocarbon receptor that induce CYP1 enzymes and other xenometabolizing activities, protects mice from AA.…”

mentioning

confidence: 99%

Cytochrome P450 1A2 Detoxicates Aristolochic Acid in the Mouse

Rosenquist¹,

Einolf²,

Dickman³

et al. 2010

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…1) For safe clinical use, it is quite necessary to evaluate the toxicity of AF and HAF since relatively high contents of AAs are found in them. Up to now, the pharmacological and toxicological actions of AAs, [4][5][6][16][17][18][19][20] A. manshuriensis [21][22][23] and A. fangchi [24][25][26] were well known, but only one piece of literature could be accessed on the subchronic toxicity of the aqueous extract of AF. 27) Drug processing is a traditional pharmaceutical technology in China, and plays an important role in reducing the toxicity of the traditional drugs.…”

Section: Acute and Subacute Toxicity Of The Extract Of Aristolochiae mentioning

confidence: 99%

Acute and Subacute Toxicity of the Extract of <i>Aristolochiae Fructus</i> and Honey-Fried <i>Aristolochiae Fructus</i> in Rodents

Jie

Huang

Ren

et al. 2014

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Aristolochiae Fructus (AF) and honey-fried Aristolochiae Fructus (HAF) have been used in China for thousands of years as an anti-tussive and expectorant drug. Few clinical cases were reported associated with the toxicity of AF and HAF, although relatively high contents of aristolochic acids (AAs) were found in them. This work was designed to compare the acute and subacute toxicity of AF and HAF in order to provide references for safe clinical use and to evaluate the possibility of reducing toxicity of AF by honey-processing. The extracts of the herb were fed to mice or rats via gastric tube. Various toxic signs and symptoms, body weights, serum biochemical assay, organ weights and histopathology were used to evaluate the toxic effects. The median lethal dose (LD 50 ) of AF and HAF are 34.1 7.2 g/kg/d and 62.6 8.0 g/kg/d with a 95% average trustable probability (p 0.95), respectively. The subacute results showed a dose-dependant relationship of the toxicity of AF and HAF. Even in the high dose groups, only moderate toxicity was observed. Honeyfrying and decoction with water can decrease the contents of AAs, and attenuate the toxic effects of AF. But sufficient attention should be still paid to the safety of AF and HAF due to the existence of AAs. Key wordsacute toxicity; subacute toxicity; Aristolochiae Fructus; honey-fried Aristolochiae Fructus; honey-frying technology; herbal safety Aristolochiae Fructus (AF), the dry-ripe fruit of Aristolochia contorta BGE. or Aristolochia debilis SIEB. et ZUCC., has been used in China for thousands of years as an anti-tussive and expectorant drug.1) Honey-fried AF (HAF) has higher frequency of use than AF in clinic.The herbs and herbal remedies containing aristolochic acids (AAs) have drawn extensive attention because they are associated with the development of a chronic, progressive renal disease, designated as aristolochic acid nephropathy (AAN).2)The AAN case was reported initially in a group of women in Belgium who developed severe renal disease after ingesting slimming pills containing Aristolochia fangchi.3) Now, AAs have been proven to be nephrotoxic, 4-6) carcinogenic [6][7][8] and mutagenic. 8,9) Therefore, most AAs-generating herbs and herbal preparations have been banned in many countries, including China. Some literatures [10][11][12][13][14][15] have reported that AAs contents in herbs were in the following order: A. manshuriensis>A. fangchi>A. Ridix>A. Fructus (AF)>A. Herbra. However, few clinical cases were reported to be associated with the toxicity of AF, AF and HAF were still listed in Chinese Pharmacopoeia (CP).1) For safe clinical use, it is quite necessary to evaluate the toxicity of AF and HAF since relatively high contents of AAs are found in them. Up to now, the pharmacological and toxicological actions of AAs, [4][5][6][16][17][18][19][20] A. manshuriensis [21][22][23] and A. fangchi [24][25][26] were well known, but only one piece of literature could be accessed on the subchronic toxicity of the aqueous extract of AF. 27)Drug processing is a traditio...

show abstract

“…Previous studies have indicated that α-Napthoflavone inhibits OS and serves potential roles is estrogen-induced breast carcinogenesis and ultraviolet-led human skin aging (27,28). β-Naphthoflavone has been demonstrated to protect mice against aristolochic acid-I-induced acute kidney injury, and to attenuate hyperoxic lung injury in premature infants primarily via mitigating OS (29,30). In the present study, α-and β-Naphthoflavone were identified to effectively antagonize the apoptosis-promoting effect of H 2 O 2 on neuronal SH-SY5Y cells.…”

Section: Discussionmentioning

confidence: 99%

α- and β-Naphthoflavone synergistically attenuate H2O2-induced neuron SH-SY5Y cell damage

Zhu

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Previous studies have demonstrated an association between neurological diseases and oxidative stress (OS).Naphthoflavone is a synthetic derivative of naturally occurring flavonoids that serves an important role in the treatment and prevention of OS-related diseases. The current study was designed to apply α-and β-Naphthoflavone individually and in combination to counteract the detrimental effects of OS on neurons in vitro. Neuronal SH-SY5Y cells were subjected to 20 µM H 2 O 2 , followed by exposure to 20 µM α-Naphthoflavone and/or 10 µM β-Naphthoflavone. Results indicated that α-and β-Naphthoflavone effectively antagonized the apoptosis-promoting effect of H 2 O 2 on neuronal SH-SY5Y cells, and that β-Naphthoflavone significantly (P<0.05) reversed H 2 O 2 -inhibited cell viability. Notably, co-treatment of α-and β-Naphthoflavone reversed the H 2 O 2 -induced apoptosis rate elevation and cell viability reduction. Further analysis demonstrated that H 2 O 2 inhibited the activities of antioxidant enzymes including catalase, superoxide dismutase and glutathione peroxidase, but this was reversed by the co-treatment with α-and β-Naphthoflavone and selectively enhanced by the treatment with α-or β-Naphthoflavone. H 2 O 2 -stimulated p38 mitogen-activated protein kinase activation was repressed following treatment with α-and/or β-Naphthoflavone, along with a decreased expression of the apoptosis-related factors and inhibited caspase-3 activation. In conclusion, co-treatment with α-and β-Naphthoflavone minimized H 2 O 2 -led neuron damage compared with treatment with α-or β-Naphthoflavone, suggesting a synergetic effect between α-and β-Naphthoflavone. This indicates that utilizing α-and β-Naphthoflavone together in the clinical setting may provide a novel therapeutic for neurological disease.

show abstract

β-Naphthoflavone protects mice from aristolochic acid-I-induced acute kidney injury in a CYP1A dependent mechanism

Cited by 29 publications

References 35 publications

Cytochrome P450 1A2 Detoxicates Aristolochic Acid in the Mouse

Cytochrome P450 1A2 Detoxicates Aristolochic Acid in the Mouse

Acute and Subacute Toxicity of the Extract of <i>Aristolochiae Fructus</i> and Honey-Fried <i>Aristolochiae Fructus</i> in Rodents

α- and β-Naphthoflavone synergistically attenuate H2O2-induced neuron SH-SY5Y cell damage

Contact Info

Product

Resources

About