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Application of Olesoxime in preparation of medicine for relieving or alleviating cis-platinum-induced acute kidney injury

A kind of acute kidney injury, cisplatin technology, applied in the field of biomedicine, can solve the problem of unreported Olesoxime association and so on

Active Publication Date: 2021-12-31
NANJING CHILDRENS HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007]There is currently no reported association between olesoxime and cisplatin-induced acute injury

Method used

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  • Application of Olesoxime in preparation of medicine for relieving or alleviating cis-platinum-induced acute kidney injury
  • Application of Olesoxime in preparation of medicine for relieving or alleviating cis-platinum-induced acute kidney injury
  • Application of Olesoxime in preparation of medicine for relieving or alleviating cis-platinum-induced acute kidney injury

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Experimental program
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Effect test

Embodiment 1

[0023] Embodiment 1 Materials and methods

[0024] 1) Materials and reagents

[0025] Olesoxime compound was purchased from MCE Company of the United States, NGAL and DRP-1 antibodies were purchased from Abcam Company, KIM-1 antibody was purchased from R&D Systems Company of the United States, Cleaved caspase3 was purchased from CST Company of the United States, β-actin, BAX, VDAC, OPA-1, ATPB, SOD2, ND1 and MPO antibodies were purchased from proteintech company. Mitotracker, mPTP, Mitosox and TMRM detection kits were purchased from Biyuntian Company. TUNEL and MDA detection kits were purchased from Novozyme, and cell apoptosis detection kits were purchased from B&D Corporation in the United States.

[0026] 2) Cisplatin-induced acute kidney injury cell model

[0027] Mouse renal tubular epithelial cells (mPTCs) were cultured in DMEM / F12 medium containing 10% fetal bovine serum at 37°C, 5% carbon dioxide and 95% air. When the mPTC grows to 70% density, change to DMEM / F12 c...

Embodiment 2

[0046] Example 2 Olesoxime improves renal injury and renal function in a cisplatin-induced acute kidney injury model.

[0047] In order to evaluate the role of olesoxime in cisplatin-induced acute kidney injury, we detected kidney-related biochemical indicators in mouse serum. After intraperitoneal injection of cisplatin for 72 hours, blood urea nitrogen and serum creatinine indicators were significantly increased, and the lumen of renal tubules was dilated. , Renal tubular epithelial cell swelling, vacuolar changes or cell shedding, basement membrane exposure, microvilli structure disappearance and other renal pathological damage are also more serious, and after Olesoxime treatment, the corresponding renal function indicators decreased significantly ( figure 1 A). In addition, renal tubular injury score also suggested that Olesoxime treatment could significantly improve renal pathological damage caused by cisplatin ( figure 1 B). These results suggest that olesoxime protect...

Embodiment 3

[0049] Example 3 In the cisplatin-induced acute kidney injury model, Olesoxime treatment improved cisplatin-induced apoptosis and inflammatory response.

[0050] In order to evaluate the detection of Olesoxime cell apoptosis in cisplatin-induced acute kidney injury, kidney tissue sections were stained with TUNEL, and the positive cells were observed under a fluorescence microscope to clarify the effect of Olesoxime on cell apoptosis ( figure 2 A), the results showed that Olesoxime could significantly improve cisplatin-induced apoptosis; further, Western blot results showed that apoptosis-related proteins Cleaved caspase3 and BAX were significantly up-regulated in the cisplatin model group, and significantly down-regulated after Olesoxime treatment ( figure 2 B).

[0051] We used qRT-PCR to detect the levels of inflammatory indicators in kidney tissue—MCP-1, TNF-α, IL-6, IL-1 ( figure 2 C), the results show that Olesoxime can significantly improve the inflammatory response ...

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Abstract

The invention discloses an application of Olesoxime in preparation of a medicine for relieving or alleviating cis-platinum-induced acute kidney injury. The Olesoxime is used on a cis-platinum mouse model and in-vitro cells for intervention treatment, the kidney structure and function of the acute kidney injury, DNA injury, renal tubular cell apoptosis and inflammatory reaction can be significantly alleviated, cisplatin-induced mitochondrial injury, cis-platinum-induced oxidative stress reaction is relieved, cis-platinum-induced mitochondrial dysfunction and the like can be alleviated, and the discovery of the invention is extremely likely to provide an effective clinical drug for AKI prevention and treatment.

Description

technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to the use of orisoxime in the preparation of medicines for alleviating cisplatin-induced acute kidney injury. Background technique [0002] In the 1970s, cisplatin began to be widely used clinically to treat a variety of malignant tumors, including bladder cancer, cervical cancer, head and neck cancer, and small cell or non-small cell lung pain. It is the most effective treatment for solid tumors. It is one of the most effective and commonly used chemotherapeutic drugs, but because cisplatin has a killing effect on tumor cells, it can also cause a series of serious adverse reactions to normal tissues and organs, which greatly limits its clinical application. The adverse reactions of cisplatin mainly include a series of systemic injury reactions such as nephrotoxicity, hepatotoxicity and hematological toxicity. Among them, nephrotoxicity is more common. After treatment with ci...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/575A61K33/243A61P13/12A61P35/00
CPCA61K31/575A61K33/243A61P13/12A61P35/00A61K2300/00
Inventor 杨运文贾占军张爱华黄松明王佩培欧阳静周宁
Owner NANJING CHILDRENS HOSPITAL
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