Potential nephroprotective effects of the Chinese herb<i>Angelica sinensis</i>against cisplatin tubulotoxicity

Bunel, Valérian; Antoine, Marie-Hélène; Nortier, Joëlle; Duez, Pierre; Stévigny, Caroline

doi:10.3109/13880209.2014.951726

Cited by 18 publications

(10 citation statements)

References 50 publications

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“…Angelica polysaccharide (ASP) is the main active component in Dang Gui with the functions of antioxidation, immune regulation, and radiation protection (21)(22)(23)(24). Our previous study showed that ASP slows down hematopoietic stem cells senescence by reducing oxidative stress (25); our other study showed that ASP could also antagonize the inhibitory effect of 5-FU on bone marrow stromal cells (2).…”

Section: Introductionmentioning

confidence: 99%

Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway

et al. 2021

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Oxidative stress induced by chemotherapeutic agents causes hepatotoxicity. 5-Fluorouracil (5-FU) has been found to have a variety of side effects, but its toxic effect on the liver and the mechanism are still unclear. Angelica polysaccharide (ASP), the main active ingredient of Dang Gui, has antioxidative stress effects. In this study, we investigated the antagonistic effects of ASP on 5-FU-induced injury in the mouse liver and human normal liver cell line MIHA and the possible mechanism. Our results show that ASP inhibited 5-FU-induced the decrease in Bcl-2 protein and the increase in Bax protein. ASP alleviated 5-FU-induced the increase in alanine aminotransferase (ALT), triglyceride (TG), and aspartate aminotransferase (AST) content; hepatic steatosis; and liver fibrosis. ASP restored 5-FU-induced swelling of mitochondria and the endoplasmic reticulum. 5-FU promoted the expression of Keap1 and increased the binding to NF-E2-related factor 2 (Nrf2) to reduce the nuclear translocation of Nrf2, thereby weakening the transcriptional activity of Nrf2 to inhibit the expression of HO-1; reducing the activity of GSH, SOD, and CAT to increase ROS content; and aggravating DNA damage (indicated by the increase in 8-OHdG). However, ASP reversed these reactions. In conclusion, ASP attenuated the 5-FU-induced Nrf2 pathway barrier to reduce oxidative stress injury and thereby inhibit the disorder of lipid anabolism and apoptosis. The study provides a new protectant for reducing the hepatic toxicity caused by 5-FU and a novel target for treating the liver injury.

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Section: Introductionmentioning

confidence: 99%

Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway

et al. 2021

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“…ASP are major effective ingredients in Chinese Angelica with significant bioactivities including antioxidant, antitumor, hematopoietic regulatory, immunomodulatory, and radiation protective effects [ 68 , 69 , 70 , 71 , 72 , 73 ]. Our recent studies indicated extraordinary anti-aging roles of ASP which protected HSPCs against radiation-induced or d -Galactose-induced aging [ 74 ].…”

Section: Introductionmentioning

confidence: 99%

Angelica sinensis Polysaccharides Ameliorate Stress-Induced Premature Senescence of Hematopoietic Cell via Protecting Bone Marrow Stromal Cells from Oxidative Injuries Caused by 5-Fluorouracil

Xiao

Xiong

Song

et al. 2017

IJMS

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Myelosuppression is the most common complication of chemotherapy. Decline of self-renewal capacity and stress-induced premature senescence (SIPS) of hematopoietic stem cells (HSCs) induced by chemotherapeutic agents may be the cause of long-term myelosuppression after chemotherapy. Whether the mechanism of SIPS of hematopoietic cells relates to chemotherapeutic injury occurred in hematopoietic microenvironment (HM) is still not well elucidated. This study explored the protective effect of Angelica sinensis polysaccharide (ASP), an acetone extract polysaccharide found as the major effective ingredients of a traditional Chinese medicinal herb named Chinese Angelica (Dong Quai), on oxidative damage of homo sapiens bone marrow/stroma cell line (HS-5) caused by 5-fluorouracil (5-FU), and the effect of ASP relieving oxidative stress in HM on SIPS of hematopoietic cells. Tumor-suppressive doses of 5-FU inhibited the growth of HS-5 in a dose-dependent and time-dependent manner. 5-FU induced HS-5 apoptosis and also accumulated cellular hallmarks of senescence including cell cycle arrest and typical senescence-associated β-galactosidase positive staining. The intracellular reactive oxygen species (ROS) was increased in 5-FU treated HS-5 cells and coinstantaneous with attenuated antioxidant capacity marked by superoxide dismutase and glutathione peroxidase. Oxidative stress initiated DNA damage indicated by increased γH2AX and 8-OHdG. Oxidative damage of HS-5 cells resulted in declined hematopoietic stimulating factors including stem cell factor (SCF), stromal cell-derived factor (SDF), and granulocyte-macrophage colony-stimulating factor (GM-CSF), however, elevated inflammatory chemokines such as RANTES. In addition, gap junction channel protein expression and mediated intercellular communications were attenuated after 5-FU treatment. Significantly, co-culture on 5-FU treated HS-5 feeder layer resulted in less quantity of human umbilical cord blood-derived hematopoietic cells and CD34+ hematopoietic stem/progenitor cells (HSPCs), and SIPS of hematopoietic cells. However, it is noteworthy that ASP ameliorated SIPS of hematopoietic cells by the mechanism of protecting bone marrow stromal cells from chemotherapeutic injury via mitigating oxidative damage of stromal cells and improving their hematopoietic function. This study provides a new strategy to alleviate the complication of conventional cancer therapy using chemotherapeutic agents.

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“…Atypical cells with significantly distorted nuclei positive for Ki-67 (a marker of cell proliferation) and phospho-histone H3 (a marker of cell division) were observed in the cisplatin-exposed organoids. Bunel et al reported that G2/M phase arrest occurred as a result of DNA damage caused by cisplatin, while the proportion of G2/M phase cells increased 23 . This finding suggests that exposure to cisplatin causes G2/M phase arrest in these organoids, and cells with atypical nuclei can be recognized prominently.…”

Section: Discussionmentioning

confidence: 99%

Kidney organoid derived from renal tissue stem cells is a useful tool for histopathological assessment of nephrotoxicity in a cisplatin-induced acute renal tubular injury model

et al. 2022

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Organoids derived from renal tissue stem cells (KS cells) isolated from the S3 segment of adult rat nephrons have previously been developed and evaluated. However, data regarding the histopathological evaluation of these organoids are limited. Therefore, in this study, we performed histopathological examinations of the properties of these organoids and evaluated the nephrotoxicity changes induced by cisplatin treatment. We observe that the tubular structure of the organoids was generally lined by a single layer of cells, in concordance with previous findings. Microvilli were exclusively observed under electron microscopy on the luminal side of this tubular structure.Moreover, the luminal side of the tubular structure was positive for aquaporin-1 (Aqp1), a marker of the proximal renal tubule. Cisplatin treatment induced cell death and degeneration, including cytoplasmic vacuolation, in cells within the tubular structure of the organoids. Cisplatin toxicity is associated with the induction of γ-H2AX (a marker of DNA damage) and the drop of phospho-histone H3 (a marker of cell division) levels. During the nephrotoxicity assessment, the kidney organoids displayed various features similar to those of the natural kidney, suggesting that it is possible to use these organoids in predicting nephrotoxicity. The histological evaluation of the organoids in this study provides insights into the mechanisms underlying nephrotoxicity.

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Potential nephroprotective effects of the Chinese herbAngelica sinensisagainst cisplatin tubulotoxicity

Cited by 18 publications

References 50 publications

Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway

Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway

Angelica sinensis Polysaccharides Ameliorate Stress-Induced Premature Senescence of Hematopoietic Cell via Protecting Bone Marrow Stromal Cells from Oxidative Injuries Caused by 5-Fluorouracil

Kidney organoid derived from renal tissue stem cells is a useful tool for histopathological assessment of nephrotoxicity in a cisplatin-induced acute renal tubular injury model

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