BIOLOGICAL TRACE ELEMENT RESEARCH
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2024
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IF 3.4
Zhao Man,Xie Longqiang,Huang Wenbin,Li Meiling,Gu Xin,Zhang Wei,Wei Jintao,Zhang Niya
Cadmium (Cd) and lead (Pb) are heavy metals prevalent in the environment and feed, and they reduce production performance of domestic animals, as well as they result in residue in animal tissues. The kidney is the target tissue for Cd and Pb. And the kidney is crucial for the reabsorption of calcium (Ca), which consequently influences bone strength. However, there are relatively few studies related to the effects of Cd and Pb exposure on performance, bone strength and kidney damage in livestock. The purpose of this experiment was to explore the combined effect of Cd and Pb on growth performance and renal impairment and the possible underlying mechanism. For this, 168 1-day-old Ross 308 broilers were randomly divided into four groups of six birds each, with seven replicates in each group: control group, 50 mg Cd/kg body weight group, 200 mg Pb/kg body weight group and 50 mg Cd/kg body weight + 200 mg Pb/kg body weight group. Feed intake was recorded daily and body weight was recorded weekly. The results show that at the end of the 3rd and 6th week, one broiler from each replicate was randomly selected for sampling. Boilers co-exposed to Cd and Pb for 3 weeks and 6 weeks had significantly decreased average daily feed intake (ADFI) and average daily body weight gain (ADG) than the control group, and the ratio of feed-to-weight gain (F/G) significantly increased after 6 weeks of co-exposure to Cd and Pb. Microscopic picture and ultrastructure analyses of the kidneys showed that Cd and Pb caused kidney damage to broiler chickens, and the damage was more serious in the Cd + Pb group, which was manifested by increased renal tubular epithelial degeneration and increased interstitial stasis points. Dietary exposure to Cd and Pb impaired production performance and induced renal oxidative damage in broilers. The combined effects of Cd and Pb on the kidneys are greater than their effects alone. The PERK-ATF4 pathway mediated endoplasmic reticulum stress participates the renal oxidative damage during chronic Cd and Pb exposure.
研究领域:
动物科学
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毒理学
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营养学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2025
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IF 3.4
Yi Cai,Liduan Huang,Yanhong Hou,Peiwen Pang,Ying Zhou,Xuan Zhang,Yiyin Long,Huajian Li,Halimulati Muhetaer,Man Zhang,Bo Wu
Andrographolide, a diterpene compound derived from the medicinal plant Andrographis paniculata , possesses anti-inflammatory, antioxidant, antitumor, and antiviral properties. Injectable formulations containing andrographolide, such as Potassium Sodium Dehydroandrographolide Succinate for Injection (PSDS), are widely used in clinical practice to treat various diseases, including upper respiratory tract infections. However, clinical reports have highlighted that andrographolide-based herbal injections may induce acute kidney injury and other renal adverse effects, thereby restricting its clinical application. Despite these concerns, the molecular mechanisms underlying andrographolide-induced nephrotoxicity remain poorly understood. In this study, we demonstrated that andrographolide induces inflammation and fibrosis in renal tubular epithelial cells and mouse kidneys. Notably, we identified for the first time that andrographolide promotes cellular senescence in renal tubular epithelial cells and mouse kidneys while downregulating the expression and enzymatic activity of SIRT3. Mechanistic investigations revealed that andrographolide mediates kidney injury and senescence through inhibition of the SIRT3/p53 signaling pathway. Furthermore, andrographolide was found to disrupt the interaction between SIRT3 and p53, resulting in increased acetylation of p53 and upregulation of its downstream target genes involved in inflammation, fibrosis, and senescence. These findings elucidate the molecular mechanisms of andrographolide-induced nephrotoxicity and provide a scientific basis for developing strategies to reduce its toxic effects.
研究领域:
药理学
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分子生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
VETERINARY RESEARCH COMMUNICATIONS
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2025
·Vol. 49
·期 5
·1-10
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IF 2
Liu Shuang,Qiu Bo,Li Yue,Wang Hai-Peng,Zhong Zhao-Jin,Wang Lin
Glyphosate (Gly) is a globally prevalent herbicide, which poses significant health risks to human and animals via the food chain. The kidney is the primary excretory organ and a site of residual accumulation during Gly exposure. Trehalose (Tre) has been shown to prevent kidney injury induced by various toxicants due to its anti-apoptotic properties. However, the potential protective effect of Tre on Gly-induced kidney damage in poultry remains unclear. Thus, 60 one-day-old healthy Hy-line Brown roosters were randomly divided into three groups ( n = 20), i.e., control group (basal diet without Gly), Gly group (200 mg Gly/kg basal diet), and Gly + Tre group {(200 mg Gly plus 5 g Tre)/kg basal diet}. The experiment lasted for 120 days, and serum and kidney samples were finally collected for respective analysis. Data first showed that Tre treatment can significantly alleviate Gly-induced renal injury in roosters, as evidenced by serum levels of creatinine and blood urea nitrogen as well as renal histopathological observations. Tre also significantly inhibited the elevated abundance of renal injury marker proteins KIM-1 and NGAL induced by Gly. Meanwhile, Tre obviously alleviated Gly-induced ultrastructural abnormalities in the nuclei of renal tissues. Additionally, Tre markedly inhibited Gly-induced apoptotic assays in rooster kidneys, as demonstrated by the results from TUNEL staining and the protein abundance of apoptotic markers cleaved caspase-3 and cleaved PARP. In summary, these findings suggest that Tre exerts its protective effects against Gly-induced kidney damage in roosters via inhibiting apoptosis.
研究领域:
毒理学
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兽医学
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分子生物学
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环境卫生
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产品关联
DOI
PubMed
高影响因子
JCI Insight
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2025
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IF 6.1
Ping Gao,Xinwei Cheng,Maochang Liu,Hui Peng,Guodong Li,Tianze Shang,Jianqiao Wang,Qianyan Gao,Chenglong Zhu,Zhenpeng Qiu,Chengliang Zhang
Tacrolimus-induced chronic nephrotoxicity (TICN) hinders its long-term use, but its mechanism remains unclear. Tacrolimus exerts its pharmacological effect by inhibiting calcineurin and its substrate NFAT. Whether the inhibition of other calcineurin substrates is related to TICN remains to be explored. Transcription factor EB (TFEB), a substrate of calcineurin, plays a crucial role in various homeostasis. Herein, we found that tacrolimus inhibited TFEB nuclear translocation and activity in mouse kidneys and HK-2 cells. Then, TFEB gain- and loss-of-function rescued the effect of tacrolimus in HK-2 cells. Furthermore, TFEB activation both by phosphorylation sites mutation and agonist rescued TICN in mice. To elucidate the mechanism of TFEB, we analyzed ChIP-seq data. Growth arrest and DNA damage-inducible 45α (GADD45α) was identified as a transcriptional target of TFEB via chromatin immunoprecipitation and dual luciferase reporter assays. And then we revealed that GADD45α overexpression rescued DNA damage and kidney injury caused by tacrolimus or TFEB knockdown in vitro, and vise versa. The protective effect of GADD45α against TICN and DNA damage was further demonstrated by overexpressing it in mice. In conclusion, the persistent inhibition of TFEB-GADD45α pathway by tacrolimus contributes to TICN. This study identifies a specific target for intervention of TICN.
研究领域:
药理学
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肾病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Guozhen Wu,Hongjing Dong,Tao Li,Chuangchuang Wang,Yingjian Guo,Lanping Guo,Xiao Wang
Hyperuricemia (HUA) is a prevalent metabolic disorder associated with chronic disease, posing significant global health challenges. Coix seed, a traditional cereal, has shown therapeutic potential against HUA, with oligosaccharides serving as its primary active components. However, the mechanisms of Coix seed oligosaccharides in HUA management remain underexplored. In this study, a novel oligosaccharide was isolated from Coix seed (CSO) through enzymatic hydrolysis and column chromatography. Structural analysis revealed that the CSO is primarily composed of glucose, with a backbone of →4)-β-Glcp-(1→ linkages. CSO exhibited significant hypouricemic effects in both adenosine-induced HK-2 cells and HUA mice by inhibiting XOD activity and regulating urate transporter expression. Furthermore, CSO restored lipid imbalances, particularly in PS and PC, and modulated gut microbiota by increasing Ruminococcus, Akkermansia, and Lachnospiraceae abundance to alleviate HUA-related systemic disturbances. Importantly, CSO alleviated HUA-induced renal injury by downregulating the IL-6/JAK2/STAT3 signaling pathway. This study provided meaningful evidence supporting the effect of CSO on HUA and offered new directions for natural oligosaccharide interventions in metabolic health.
研究领域:
营养学
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代谢组学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Yuan Ning,Ping Chen,Zhengnan Shen,Xing Liu,Huan Gu
Cisplatin (CDDP) is commonly used as an anticancer drug in clinical practice, but severe nephrotoxicity restricts it from exerting anticancer effects. Natural drugs, such as resveratrol, can alleviate the side effects of cisplatin, but their low solubility and gastrointestinal effects prevent them from working. Herein, we developed nanoparticles for kidney injury consisting of a biocompatible material, zein, as a carrier. HA-Zein/Res NPs were fabricated using low-molecular-weight hyaluronic acid coatings. This preparation is non-cytotoxic to renal tubular epithelial cells and can be used with confidence. Low-molecular-weight hyaluronic acid has inflammation-targeting properties and CDDP damage causes renal inflammation. Owing to this property of the low-molecular-weight hyaluronic acid coating, in vivo imaging experiments in mice demonstrated that the HA-Zein/Res NPs enabled more nanoparticles to accumulate in the renal sites affected by inflammation. Efficient resveratrol delivery alleviated kidney injury, and experiments demonstrated that HA-Zein/Res NPs could treat kidney injury while reducing the serum creatinine and urea nitrogen levels in mice. Collectively, these results indicated that this nanomaterial is a promising agent for reducing the clinical nephrotoxicity of cisplatin.
研究领域:
药学
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生物医学工程
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毒理学
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产品关联
DOI
PubMed
高影响因子
PROCESS SAFETY AND ENVIRONMENTAL PROTECTION
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2025
·
IF 7.8
Yafang Li,Jia Wei,Xiaofang Liang,Jiangping Wang,Sisi Yan,Lemei Zhu,Zhen Ding,Chunhua Zhan,Xiaoya Ren,Fei Yang
Microcystin-LR (MC-LR) is a widely distributed cyanotoxin that causes kidney injury. Our previous work identified Sphingopyxis sp. YF1 as a novel bacterial strain capable of efficiently degrading MC-LR, but its protective role and mechanisms against MC-LR-induced kidney injury remain unexplored. In this study, the bioactive metabolite of strain YF1 was identified by mass spectrometry. The beneficial effect of strain YF1 and its bioactive metabolite against MC-LR-induced kidney injury was validated in vivo and in vitro . We found strain YF1 effectively ameliorated MC-LR induced kidney disruption and functional impairment. Mechanistically, strain YF1 significantly improved oxidative stress (SOD, CAT, GSH, and MDA) and inhibited pro-inflammatory factors expression (including IL-6 , IL-18 , IL-1β , and TNF-α ) induced by MC-LR. Notably, strain YF1 not only reduce MC-LR level in mice but also produce a bioactive metabolite astaxanthin. Consistently, both in vivo and in vitro experiments demonstrated that astaxanthin alleviated MC-LR-induced kidney injury by modulating antioxidant pathways and inflammatory cascades. This study suggested that strain YF1 could alleviate MC-LR-induced kidney injury by removing MC-LR and generating astaxanthin that mediated antioxidant and anti-inflammatory effects. These findings highlighted microbial-based antidotes for simultaneously eliminating MC-LR and mitigating its harmful effects.
研究领域:
环境生物学
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毒理学
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微生物学
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产品关联
DOI
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Lijiao Zhao,Heyun Zhu,Haoye Li,Shuaihao Guo,Jingchun Wang,Zhaoxin Tang,Jianzhao Liao,Jianying Guo
Nano-copper (nanoCu), a nanoscale form of copper (Cu), has been widely applied in the animal husbandry industry. However, it is of great concern that the Cu exposure to humans and animals can cause toxic damage to multiple organs. Hesperidin (Hes), a flavonoid found in citrus fruits, has shown mitigating effects on various organ damages. In our study, we aimed to investigate the toxic effects of nanoCu exposure on the kidneys of chickens and the therapeutic efficacy of Hes in nanoCu-induced renal injury. Our results indicated that Hes could alleviate endoplasmic reticulum stress (ERS) caused by nanoCu exposure. Intriguingly, nanoCu significantly disrupted endoplasmic reticulum (ER) homeostasis, which manifested as increased levels of key proteins such as GRP78, PERK, and CHOP, as well as elevated H 2 O 2 levels. But Hes treatment exhibited an opposite trend. Furthermore, nanoCu significantly induced autophagy in renal cells, which was accompanied by the activation of the AMPK-AKT/mTOR pathway and a concurrent increase in the protein levels of ATG5, Beclin 1, LC3 Ⅱ/LC3 Ⅰ, and ULK1, along with a decrease in the level of p62. However, it can be reversed by Hes treatment. These findings suggest that Hes could mitigate ER homeostasis disruption and autophagy caused by nanoCu exposure, providing new insights into the pharmacological treatment of Hes in related health issues.
研究领域:
动物医学
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毒理学
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药理学
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产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2025
·
IF 7.7
Yue-Yang Zhang,Le-Yu Huang,Huiling Wang,Sixuan Meng,Fei Yang,Shi-Yu Liu
Carboxylesterase 2 (CES2), an extensively expressed serine esterase which widely distributed in various organs and tissues, exerts important roles in maintaining normal physiological function while abnormal expression of CES2 was correlated with many metabolic diseases and cancers. Thus, to develop efficient tool for detection of CES2 activity is of great importance in related clinical diagnosis and research of physiological function of CES2. To date, several enzyme-activated fluorescent probes were developed for CES2 sensing. Among which regulation of CES2 in diseases such as diabetics, colitis, cancers and liver injury could be visualized. However, even though CES2 displayed relatively high expression level in kidney, its regulation in pathological process of kidney injury was rarely studied, and thus related preliminary investigation is in urgent demand. Herein, by rational design and construction of an enzyme-activated fluorescent probe (named as DDXB ) with high catalytic efficacy, sensitivity and specificity toward CES2, down-regulation of CES2 activity in acetaminophen (APAP)-induced liver injury and dextran sulfate sodium (DSS)-induced colitis model was successfully visualized. Most importantly, aberrant up-regulation of CES2 in streptozotocin (STZ), renal ischemia reperfusion (IR) injury (RIRI) and cisplatin (CDDP)-induced kidney injury model was first revealed via DDXB- based fluorescence imaging and further confirmed by immunohistochemistry (IHC) staining. Thus, preliminary evidence for identifying CES2 as potential biomarker of kidney injury were first provided, and the newly developed probe could serve as an efficient tool for related diagnosis or further investigation of CES2 physiological function in more diseases.
研究领域:
生物化学
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医学诊断
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病理学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Yanan Zhao,Rui Wang,Ran Cao,Leyao Chen,Lei Chen,Hui Teng
Hyperuricemia (HUA) is often associated with renal injury and intestinal flora disturbance. Galangin, a polyphenolic compound found in Alpinia officinarum and propolis, has demonstrated the capacity to inhibit xanthine oxidase (XO) activity both in vitro and in silico; however, the precise mechanisms underlying its effects in vivo remain unclear. This study aims to investigate the effect of galangin on uric acid (UA) metabolism as a prospective strategy for lowering UA and further explore the underlying mechanisms. Galangin mitigates kidney tissue injury and fibrosis, reduces the serum UA level via inhibiting UA synthesis in the liver, and promotes UA excretion in the kidney. Molecular docking results also uncovered the structure–activity relationship of galangin and the UA transporters GLUT9, URAT1, ABCG2, and OAT1, implying a potential interaction. Also, galangin mitigated the HUA-activated NF-κB/MAPK signaling pathway in the kidney, as well as colon tissue damage and barrier dysfunction, which are closely linked to deteriorated intestinal permeability. Moreover, galangin remedied the alterations in intestinal microecology caused by HUA, encompassing changes in the structure and composition of gut microbial species as well as the metabolism of SCFAs. Collectively, this study demonstrates that galangin exerted an improvement on HUA by ameliorating gut–kidney axis dysfunction.
研究领域:
药理学
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代谢生物学
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肾脏病学
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微生物组学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
You Zhou,You Wu,Rui Zhu
Background Septic acute kidney injury (S-AKI) is a major cause of acute kidney injury (AKI), but no effective therapies exist to prevent or treat it. Although KLF6 is linked to various pathophysiological processes, its exact role in S-AKI is not yet fully understood. Methods The role of KLF was investigated using both the mouse CLP model and in vitro systems. To identify the transcriptional targets regulated by KLF6, ChIP-qPCR and luciferase reporter assays were carried out. Biochemical and cellular techniques were employed to assess cellular injury and lipid peroxidation levels. The extent of ferroptosis was evaluated through transmission electron microscopy (TEM). Results KLF6 levels were significantly increased in a renal IRI model. Knockdown of KLF6 using AAV9 reduced kidney injury in both in vitro and in vivo models, while KLF6 overexpression aggravated injury. Overexpression of KLF6 promoted ferroptosis, whereas its knockdown reduced lipid peroxidation and ferroptosis. KLF6 regulates NCOA4 expression by binding to its promoter, controlling ferroptosis. Knockdown of NCOA4 in vitro alleviated ferroptosis and cellular damage caused by KLF6 overexpression. Pharmacological inhibition of KLF6 reduced kidney injury and ferroptosis in S-AKI mice. Conclusion Our study uncovered a previously unrecognized role for KLF6 in S-AKI. By facilitating NCOA4 transcription, KLF6 intensified ferroptosis, which, in turn, aggravated septic AKI.
研究领域:
肾脏病学
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分子生物学
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病理生理学
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细胞生物学
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转录调控
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2021
·
IF 4.451
Xizhu Wang,Liyan Yuan,Zhijie Bao,Baoshang Fu,Pengfei Jiang,Tiecheng Ma,Songyi Lin
To screen the in vitro uric acid-lowering activity of the neutral polysaccharides (NCSP) and acid polysaccharides (ACSP) isolated from the corn silk were evaluated. Furthermore, preliminary structure-activity relationships for them were investigated. The molecular weight (Mw) of NCSP and ACSP were 74.1 and 109.4 kDa, respectively. NCSP consisted of mannose (Man), glucuronic acid (GlcA), glucose (Glc), galactose (Gal), and arabinose (Ara), in addition to these monosaccharides, the ACSP contains galactose acid (GalA). NMR spectroscopy showed that the NCSP main chain consisted of 1,4,6)- α -D-Glc p , 1,4)- α -D-Glc p , 1,3)- β -D-Gal p , and 1,3,5)- β -D-Man p . NCSP exhibited higher activity in anti-hyperuricemia (HUA). The results indicated that serum uric acid (UA) and liver xanthine oxidase (XO) activities levels decreased by 45.71% and 22.4% in the NCSP groups, respectively. In addition, NCSP could significantly improve the kidney damage and promote uric acid excretion. These findings provide evidence in support of NCSP as a potential dietary supplement for improving HUA.
研究领域:
药理学
·
生物化学
·
营养学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）