Multi modular toxicity assessment of nephrotoxicity in podophyllotoxin exposure rats on account of toxicological evidence chain (TEC) concept

Kong, Juanjuan; He, Tao; Liu, Chuanxin; Huang, Jianmei

doi:10.1016/j.ecoenv.2021.113157

Cited by 12 publications

(3 citation statements)

References 41 publications

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“…In particular, serum creatinine and BUN levels are the commonly used as the main markers in the clinical evaluation of glomerular filtration function. 42 BUN is the principal nitrogen-containing metabolic product of protein catabolism, which serves as a biochemical marker of renal function, renal damage, and evaluation of the function of the nephrons. 43 Creatinine, a nonprotein nitrogenous substance, is a metabolic product formed from phosphocreatine and creatinine during muscle metabolism and is excreted in the urine.…”

Section: Discussionmentioning

confidence: 99%

The ameliorative effects of quercetin and curcumin against subacute nephrotoxicity of fipronil induced in Wistar rats

Uzunhisarcıklı

Apaydın

Baş

et al. 2023

Toxicology Research

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Fipronil is a phenylpyrazole insecticide that is widely used in agricultural, veterinary, and public health fields for controlling a wide variety of insect species and it is an environmentally potent toxic substance. Curcumin and quercetin, which are well-known natural antioxidants, are widely used to prevent the harmful effects of free radicals on biological systems. The present study aimed to determine the potential ameliorative effects of quercetin and/or curcumin on fipronil-induced nephrotoxicity in rats. Curcumin (100 mg/kg of body weight), quercetin (50 mg/kg of body weight), and fipronil (3.88 mg/kg of body weight) were administered to male rats by intragastric gavage for 28 consecutive days. In the present study, body weight, kidney weight, the renal function markers (blood urea nitrogen, creatinine, and uric acid levels) in the blood, antioxidant enzyme activities, and malondialdehyde level as markers of oxidative stress, and histological changes of the renal tissue were evaluated. The levels of serum blood urea nitrogen, creatinine, and uric acid were significantly increased in fipronil-treated animals. Additionally, while superoxide dismutase, catalase, glutathione-S-transferase, and glutathione peroxidase activities were decreased in the kidney tissue of rats treated with fipronil, malondialdehyde level was significantly increased. Histopathological analyses showed that the glomerular and tubular injury occurred in the renal tissue of fipronil-treated animals. Also, the supplementation of quercetin and/or curcumin with fipronil significantly improved fipronil-induced alterations in renal function markers, antioxidant enzyme activities, malondialdehyde levels, and histological features of renal tissue.

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Section: Discussionmentioning

confidence: 99%

The ameliorative effects of quercetin and curcumin against subacute nephrotoxicity of fipronil induced in Wistar rats

Uzunhisarcıklı

Apaydın

Baş

et al. 2023

Toxicology Research

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“…4 weeks-old male rats (170–220 g) were selected ( n = 3) to evaluate the toxicity of the nanocomposites. 49 These animal experiments were approved by the Ethics Committee of Qingdao Stomatological Hospital (2023KQYX027) and complied with the regulations on the management of experimental animals. The control group was given single steaming water.…”

Section: Methodsmentioning

confidence: 99%

CHN nanocomposites and nanocoating resist enamel white spot lesions by enhancing remineralization and antibacterial activity

Wang,

Niu,

et al. 2024

RSC Adv.

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“…The integration of transcriptomics and metabolomics is considered an impactful approach for discovering potential biomarkers or key genes (Arend et al, 2022; Yang et al, 2022), increasingly applied in disease screening (Jha et al, 2015), and safety assessment (Kong, He, Liu, & Huang, 2022). Association analyses of gene expression profiles and metabolite profiles could provide a systematic understanding of toxic processes as well as mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomics and metabolomics reveal the role of CYP1A2 in psoralen/isopsoralen‐induced metabolic activation and hepatotoxicity

Zhang

Song

Zhao

et al. 2022

Phytotherapy Research

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Psoralen and isopsoralen are the pharmacologically important but hepatotoxic components in Psoraleae Fructus. The purpose of this study was to reveal the underlying mechanism of psoralen/isopsoralen‐induced hepatotoxicity. Initially, we applied integrated analyses of transcriptomic and metabolomic profiles in mice treated with psoralen and isopsoralen, highlighting the xenobiotic metabolism by cytochromes P450 as a potential pathway. Then, with verifications of expression levels by qRT‐PCR and western blot, affinities by molecular docking, and metabolic contributions by recombinant human CYP450 and mouse liver microsomes, CYP1A2 was screened out as the key metabolic enzyme. Afterwards, CYP1A2 induction and inhibition models in HepG2 cells and mice were established to verify the role of CYP1A2, demonstrating that induction of CYP1A2 aggravated the hepatotoxicity, and conversely inhibition alleviated the hepatotoxic effects. Additionally, we detected glutathione adducts with reactive intermediates of psoralen and isopsoralen generated by CYP1A2 metabolism in biosystems of recombinant human CYP1A2 and mouse liver microsomes, CYP1A2‐overexpressed HepG2 cells, mice livers and the chemical reaction system using UPLC‐Q‐TOF‐MS/MS. Ultimately, the high‐content screening presented the cellular oxidative stress and relevant hepatotoxicity due to glutathione depletion by reactive intermediates. In brief, our findings illustrated that CYP1A2‐mediated metabolic activation is responsible for the psoralen/isopsoralen‐induced hepatotoxicity.

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Multi modular toxicity assessment of nephrotoxicity in podophyllotoxin exposure rats on account of toxicological evidence chain (TEC) concept

Cited by 12 publications

References 41 publications

The ameliorative effects of quercetin and curcumin against subacute nephrotoxicity of fipronil induced in Wistar rats

The ameliorative effects of quercetin and curcumin against subacute nephrotoxicity of fipronil induced in Wistar rats

CHN nanocomposites and nanocoating resist enamel white spot lesions by enhancing remineralization and antibacterial activity

Transcriptomics and metabolomics reveal the role of CYP1A2 in psoralen/isopsoralen‐induced metabolic activation and hepatotoxicity

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