35 results about "Hepatic toxicity" patented technology

The invention discloses application of polydatin in preparation of a medicine for relieving hepatotoxicity caused by zearalenone, and belongs to the technical field of biological medicine. The invention reveals that polydatin inhibits hepatotoxicity caused by zearalenone through targeted xanthine oxidase for the first time, so that the toxicity of zearalenone to an organism is relieved. Polydatin can be directly combined with xanthine oxidase to inhibit the catalytic activity of xanthine oxidase, so that the oxidative stress injury of the liver after ZEA exposure is reduced, meanwhile, the content of malondialdehyde (MDA) in the liver can be remarkably reduced, the activity of superoxide dismutase (SOD) is improved, the liver oxidation-antioxidant balance is recovered, and liver cells are protected from oxidative injury of ZEA. The invention provides a new scientific basis and development direction for application of polydatin in the fields of mycotoxin detoxification, oxidation resistance, liver protection and the like.

The application provides a method for analyzing the synergistic mechanism of hepatotoxicity and nephrotoxicity of non-steroidal anti-inflammatory drugs. The method comprises the following steps: preliminary toxicity prediction of NSAIDs and collection of toxicity target points, collection of liver and kidney disease target points, then cross and screening of the target points to obtain core target points and common core target points of NSAIDs induced liver and kidney diseases, and then constructing a protein interaction network of the common core target points; enrichment analysis of the common core target points to obtain the common action pathway of NSAIDs induced liver and kidney diseases; finally, further screening of the common core target points to obtain the key target points of NSAIDs induced liver and kidney diseases, and verification by using molecular docking technology. Compared with the traditional method, the advantages of the method are: first, the method does not depend on large-scale patient clinical data and a large number of animal or cell experiments, avoiding the ethical controversy in animal experiments and human experiments; second, the method can identify the potential cross-pathway and synergistic toxicity mechanism when a compound triggers multiple diseases, which is helpful for more comprehensive evaluation of the toxicity risk of NSAIDs.

The present application relates to a method for constructing a human acute liver injury and chemotaxis model based on a normal liver organoid and application thereof. Specifically, the present application provides a method for constructing a human liver organoid; further, contacting the liver organoid with a hepatotoxic drug can construct a human acute liver injury model; co-culturing the organoid or the injury model with immune cells can construct an in vitro immune cell chemotaxis model. The present application also provides reversible immunoaffinity magnetic beads for isolating VSIG4-positive macrophages and a method for isolating the same. The human liver organoid, acute liver injury model and chemotaxis model of the present application can be used for screening drugs for treating acute liver injury, evaluating the hepatotoxicity of compounds, researching the pathogenesis of acute liver injury and evaluating the effect of immunomodulatory drugs.

The application provides a drug hepatotoxicity prediction method, device, system and medium, the method comprising: sequencing human liver cells after being contacted with a drug to be predicted to obtain a genome expression profile of the human liver cells after being contacted with the drug to be predicted; calculating the sum of the absolute values of the fold changes of the genes in the current gene pathway as the toxicity score of the current gene pathway according to the expression profile; calculating the Z value of the current gene pathway according to the toxicity score of the current gene pathway, the average value and the standard deviation value of the toxicity scores of the gene pathways calculated multiple times by a plurality of preset gene pathways; and predicting that the drug to be predicted has hepatotoxicity when the Z value is greater than 1.5. Therefore, the application can accurately, timely, effectively and sensitively predict drug hepatotoxicity without a large number of living animals as an experimental basis, and has good advantages in safety, environmental protection and animal protection. The application has the advantages of short experimental period and low cost.

The invention discloses a medicine for preventing or treating liver toxic and side effects of osimertinib, and belongs to the technical field of medicines. Aiming at liver toxic and side effects caused by osimertinib, the invention provides an effective therapeutic drug, and the autophagy inhibitor relieves death caused by excessive activation of an autophagy pathway in hepatocytes by inhibiting autophagy activated by osimertinib, so that hepatotoxicity caused by osimertinib is relieved. The autophagy inhibitor and osimertinib are combined, so that the survival rate of hepatocytes can be remarkably improved, and liver injury caused in the osimertinib treatment process is reduced. The invention further provides novel application of the hydroxychloroquine or the S-adenosylmethionine in preparation of the medicine for preventing or treating the liver toxic and side effects of the osimertinib, the hydroxychloroquine or the S-adenosylmethionine has a remarkable treatment effect on liver injuries caused by the osimertinib, the medication safety of the hydroxychloroquine or the S-adenosylmethionine is high, and the hydroxychloroquine or the S-adenosylmethionine can be used for preparing the medicine for preventing or treating the liver toxic and side effects of the osimertinib. Good development prospects are realized.

The invention discloses application of physcion in preparation of a medicine for reducing liver cell lipid deposition, and particularly relates to application of physcion in preparation of a medicine for preventing and treating lipid deposition fatty liver. In-vitro cell experiments prove that the physcion shows low toxicity and a wide safety range in a human normal hepatocyte line THLE3, a human hepatoma cell line HepG2 and a mouse normal hepatocyte line AML12, and can obviously reduce the level of oleic acid-induced intracellular triglyceride in a dose-dependent manner, so that the physcion can be used for preparing a medicine for treating liver cancer. Oil red O staining results also visually show that lipid droplet accumulation in cells can be effectively reduced; according to the invention, the technical prejudice that the emodin monomethyl ether is regarded as a potential hepatotoxic component in the prior art is overcome, a safe and effective new choice is provided for the treatment of the lipid deposition fatty liver, and the pharmaceutical composition has a wide clinical application prospect.

Systems and methods consistent with the present invention generally relate to microorganospheres (MOSs), and methods and apparatuses for forming and using MOSs. More particularly, in some embodiments, systems and methods consistent with the invention relate to the methods and apparatuses for forming and using MOSs generated from hepatocytes. MOPSs that are generated from hepatocytes are suitable for testing liver toxicity and drug induced liver injury effects of various agents.

The invention belongs to the field of antitumor drugs, and particularly relates to a targeted 4-1BB aptamer and application of the targeted 4-1BB aptamer in preparation of antitumor drugs. A target 4-1BB nucleic acid aptamer is obtained through screening, the sequence of the target 4-1BB nucleic acid aptamer is shown as SEQ ID No.1, and the target 4-1BB nucleic acid aptamer is specifically 5 '-CACGCATAACATGTATGGACTGCTCGGGATTGCGG ATTTACATTCGTTATGCGTG-3', the sequence of the target 4-1BB nucleic acid aptamer is shown as SEQ ID No.1, and the sequence of the target 4-1BB nucleic acid aptamer is shown as SEQ ID No.1. The nucleic acid aptamer has a good application effect in preparation of anti-tumor drugs. The capacity of the aptamer for inhibiting mouse Hepa1-6 subcutaneous tumor is superior to that of mouse 4-1BB agonist antibody drugs with the same total mass. The obvious hepatotoxicity and visceral toxicity are not found; growth of mouse Hepa1-6 liver in-situ cancer can be inhibited, and the proportion of CD8 + T cells in T cells in the liver can be increased.

The present invention discloses the use of a short-term embolic agent in reducing drug accumulation in the liver, hepatic clearance and / or liver toxicity. The present invention provides the use of a short-term embolic agent in the manufacture of a medical composition for: (a) temporarily embolizing blood vessels supplying the liver; and (b) reducing the accumulation of a drug subsequently or concurrently administered intravenously in the liver. The strategy aims to minimize the exposure of a drug (such as LNP) to the liver by temporarily blocking the blood supply to the liver via the portal vein and / or arteries. The present invention significantly reduces the non-specific accumulation of a drug in the liver by temporarily blocking the portal vein, arterial and / or their branch blood flow, thereby greatly reducing the opportunity for the drug to enter the liver from a hemodynamic root.

The invention discloses an ovarian anti-aging cell biological agent and a preparation method and application thereof, and belongs to the technical field of biology, ovarian stem cells and mulberry-source specific polypeptides SEQ ID NO.1 and SEQ ID NO.2 are compounded to obtain the biological agent, a cell repair and molecular regulation dual mechanism is formed, animal experiments show that the efficiency of promoting E2 secretion and inhibiting FSH secretion of the biological agent is improved, and the biological agent has a good application prospect. Moreover, the survival rate of follicles under a microscope is remarkably improved, and a relatively good treatment prospect is shown in the aspect of ovarian aging resistance. Meanwhile, mulberry with homology of medicine and food is adopted to replace polygonum multiflorum to extract active ingredients, and the risk of hepatotoxicity is avoided.

This invention relates to the field of livestock and poultry breeding and food safety testing technology, and in particular to a method for assessing copper exposure hepatotoxicity based on the endoplasmic reticulum stress-endoplasmic reticulum autophagy axis and its application. This method obtains liver tissue samples or in vitro cultured hepatocyte samples from copper-exposed subjects, and jointly detects the expression levels of key markers of the endoplasmic reticulum stress pathway and characteristic markers of the endoplasmic reticulum autophagy pathway. Combined with two-way pharmacological validation, a grading assessment standard for copper exposure hepatotoxicity is established. This invention overcomes the shortcomings of traditional liver enzyme indicators, such as low sensitivity and strong lag, and has the advantages of early warning, high specificity, and reliable results. It can be widely applied to scenarios such as determining the copper safety threshold in livestock and poultry feed, early screening for copper exposure hepatotoxicity, assessment of copper pollution ecological risks, and screening of copper toxicity protectants, providing technical support for ensuring animal health and the safety of animal-derived food.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a tripterine prodrug compound as well as a preparation method and application thereof. The tripterine prodrug compound provided by the invention has a structure as shown in a formula I. The tripterine prodrug compound designed by utilizing the unique high expression characteristic of nitrate reductase in a tumor microenvironment can be specifically activated by the nitrate reductase at a tumor part, so that accurate release of tripterine at the tumor part is realized; the tripterine prodrug compound is kept relatively stable in normal tissues, so that the toxic effect on tissues such as normal livers is greatly reduced, and an innovative and potential solution is provided for solving the hepatotoxicity problem of the tripterine and improving the anti-tumor treatment effect of the tripterine; and breakthrough is hopefully brought to tumor treatment and the clinical application value is improved. Formula I.

Methods and uses are disclosed for treating a subject suffering from a disorder selected from a liver disorder, Cushing's syndrome, or Cushing's Disease, cancer, an infection, an inflammatory condition, a cardiovascular, endocrine, or kidney disease, and combinations thereof, or other disorder for which they may be administered a drug which may cause liver toxicity, without adverse effects on the liver. Such liver disorders include fatty liver diseases are effective for reducing high levels of liver enzymes with a favorable safety profile. The methods and uses comprise administering to the subject an effective amount of a selective nonsteroidal glucocorticoid receptor modulator such as relacorilant, including methods and uses in combination with another drug, without adverse effects on liver enzyme levels, or on liver function. In embodiments, the other drug may be a drug that may cause liver toxicity, such as drugs that inhibit CYP3A enzymes, e.g., itraconazole or ketoconazole.

The invention discloses a multi-modal hepatotoxicity prediction model determination method, and belongs to the technical field of big data processing. The method comprises the following steps: acquiring a drug-determination matrix of N rows and M columns, wherein the N rows comprise drug data of N drugs; the M column comprises measurement data of whether the medicine has a biological activity label or not under each target of the M targets; mapping K candidate determination data related to hepatotoxicity and F basic hepatotoxicity mechanism frameworks in the drug-determination matrix to obtain a biological fingerprint; determining heterogeneous data corresponding to each drug according to the chemical structure chart and the biological fingerprint of each drug in the N drugs; according to the drug data and the heterogeneous data of each drug, training the neural network prediction model until a preset training condition is met, and obtaining a multi-modal hepatotoxicity prediction model. Therefore, the cost of determining the hepatotoxicity of the compound can be effectively reduced without depending on experimental animals and manual operation, and the efficiency and accuracy of determining the hepatotoxicity of the compound are improved.

The invention discloses an application of a hispiraceae bacterium in preparation of a medicine for relieving the hepatotoxicity of saikoside D, and relates to the field of medicines. According to the invention, an intestinal bacterium with a specific antagonistic effect on the hepatotoxicity of saikoside D is identified and applied for the first time. The limitation that non-specific regulation is carried out through broad-spectrum probiotics or complex compounds traditionally is broken through, and the crossing from'macroscopic flora regulation 'to'key strain targeting' is realized. The strategy directly aims at a key link of SSd toxicity generation, the liver can be effectively protected, meanwhile, the core drug effect of SSd can be reserved to the maximum extent, and the final goal of toxicity reduction and effect storage is really achieved.

The application discloses a vortioxetine impurity, a preparation method and application thereof, and adopts vortioxetine or a pharmaceutically acceptable salt form thereof as raw material, the raw material is easy to obtain and simple to operate, and the reaction condition is mild. The synthesized impurity is characterized by nuclear magnetic resonance, high-resolution mass spectrometry and X-ray single crystal diffraction, and liver toxicity research shows that the compound disclosed by the application has important significance for researching adverse reactions of vortioxetine. The control sample obtained by the method provided by the application can be used for qualitative and quantitative analysis of the vortioxetine impurity, so that the drug safety of vortioxetine is improved.

This disclosure relates to a method for establishing a HepaRG-based differentiated liver 3D microsphere model and its applications. Specifically, this disclosure provides a chemically defined differentiation medium formulation that does not require DMSO and contains hepatocyte growth factor, dexamethasone, and hepatoprotectin M. Using this medium, HepaRG cells can be efficiently induced to form compact, long-lived 3D microspheres in ultra-low adsorption 96-well plates or in conjunction with high-throughput 3D printing technology. After differentiation and maturation, the model can stably express hepatocyte markers, key drug-metabolizing enzymes, and nuclear receptors at high levels. The liver 3D microsphere model established by this disclosure can effectively simulate hepatocyte function in vivo and is suitable for high-throughput drug hepatotoxicity screening. The results show a high degree of consistency with clinical hepatotoxicity data, and it has important application value in the field of drug safety evaluation.

The invention discloses an application of a composition containing a semen raphani extract in enhancing the anti-tumor curative effect of paclitaxel (PTX), and particularly discloses a composition containing a semen raphani extract and an application of the composition containing the semen raphani extract in enhancing the anti-tumor curative effect of PTX. Researches show that the composition containing the semen raphani extract can synergistically enhance the anti-lung cancer curative effect of PTX, can significantly inhibit the growth of tumors, reduce the size of the tumors, reduce the expression of a proliferation marker Ki67 in the tumors, promote lung cancer cell apoptosis and also can improve the pathological morphology of tongue tissues after combined medication; the composition has no obvious influence on tumor model animals by singly adopting the composition, and the combined use of the two can not only obviously enhance the curative effect of PTX, but also reduce toxic and side effects caused by PTX, repair taste structural damage and taste disorder caused by PTX, and also relieve hepatotoxicity caused by PTX administration. The combined medication scheme provided by the invention not only can enhance the anti-tumor curative effect of PTX, but also can reduce toxic and side effects caused by PTX, has good safety, and provides a safer and more efficient method and means with lower toxic and side effects for the combined medication scheme of anti-tumor drugs.

The present disclosure relates to the field of pharmacy and medicine, in particular to a method for constructing a drug hepatotoxicity prediction model and its application in predicting drug hepatotoxicity, further relates to a method, system and device for predicting drug hepatotoxicity, and further relates to the use of a combination of cell phenotype parameters in predicting drug hepatotoxicity. The method for predicting drug hepatotoxicity provided by the present disclosure can identify the toxicity of a drug to be tested on hepatocytes by performing high-content analysis test experiments on hepatocytes in at least 3 groups (7 parameters) and at most 6 groups (13 parameters), combined with the drug human body exposure C max value, i.e. the toxicity of the drug to be tested on hepatocytes can be identified, and the accuracy of the method can be up to 87%, and the highest sensitivity and specificity are 84% and 94% respectively, which are significantly higher than the reported prediction methods based on HCA or other technologies.

The invention discloses a medicine for treating hepatotoxicity of bosutinib by taking a CAMK2G gene or protein as a target spot, and belongs to the technical field of medicines. According to the medicine, the hepatotoxicity of bosutinib is relieved by down-regulating the expression of the CAMK2G gene or restoring the phosphorylation of the CAMK2G protein. The invention reveals that the CAMK2G gene is a key gene of liver injury and abnormal glucose metabolism caused by bosutinib, and provides a new prevention and treatment target for intervening hepatotoxicity caused by bosutinib. According to the invention, the CAMK2G phosphorylation activator is utilized to recover CAMK2G phosphorylation to relieve liver injury and abnormal glucose metabolism, a new direction is provided for finding an intervention strategy for causing hepatotoxicity by drugs, and the current situation that few intervention drugs can be used clinically and the mechanism is single is solved to a certain extent.

The invention discloses RNAi for reducing the hepatotoxicity of triptolide and application of the RNAi, and belongs to the technical field of biological medicine. According to the invention, siRNA of a targeted Cyp2e1 gene is subjected to 2 '-O methyl modification and dTsdT 3' phosphorothioate connection modification, and then is delivered through lipid nanoparticles (LNPs). After intravenous injection administration, mouse liver Cyp2e1 protein expression can be reduced by 70% or above within 24 h, and subacute liver injury induced by triptolide can be remarkably relieved by reducing the level of serum glutamic-pyruvic transaminase / aspartate transaminase, inhibiting liver oxidative stress and reducing release of inflammatory factors such as TNF-alpha / IL-1beta / IL-6. According to the invention, the defect that the drug effect is reduced or the targeting property is poor in the existing toxicity attenuation scheme is overcome, a clinical auxiliary toxicity attenuation technical scheme with remarkable targeting regulation effect and high safety is provided, and a new path is provided for safe clinical application of triptolide.

The application discloses an ovarian anti-aging cell biological preparation and a preparation method and application thereof, and belongs to the technical field of biotechnology. The biological preparation is obtained by compounding ovarian stem cells and mulberry source specific polypeptides SEQ ID NO. 1 and SEQ ID NO. 2, a double mechanism of cell repair and molecular regulation is formed, animal experiments show that the efficiency of promoting E2 secretion and inhibiting FSH secretion is improved, and the follicle survival rate under a microscope is significantly improved, and the ovarian anti-aging aspect embodies a good treatment prospect. Meanwhile, the application adopts the medicinal and edible mulberry to replace the active ingredients extracted from radix falcaliae polygoni multiflori, and avoids the hepatotoxicity risk.

A method for screening the compounds for susceptibility to causing systemic or hepatotoxicity. [Solution] A method comprising the steps of providing a compound to be screened, establishing a hepatic cell line (HCS) capable of bile acid synthesis, bile acid transport and / or bile acid regulation, exposing the hepatic cell line (HCS) to a range of concentrations of bile acids to determine the toxicity profile of the bile acids, wherein the bile acid toxicity profile includes toxic potency, exposing the hepatic cell line (HCS) to a range of concentrations of bile acids in the presence of the compound to be screened and determining the toxicity profile of the bile acids, wherein the bile acid toxicity profile includes toxic potency, and comparing the toxic potencies of the bile acids to determine the susceptibility of the compound to causing systemic toxicity and / or hepatotoxicity.

The invention provides a method for analyzing a combined action mechanism of hepatotoxicity and renal toxicity of a non-steroidal anti-inflammatory drug. The method comprises the following steps: preliminary toxicity prediction of NSAIDs, toxic action target collection, liver and kidney disease target collection, target crossing and screening to obtain a core target and a common core target of the NSAIDs induced liver and kidney diseases, and further constructing a protein interaction network of the common core target. Carrying out enrichment analysis on the common core target spot to obtain a common action way of inducing the liver and kidney diseases by the NSAIDs; and finally, further screening the common core target spot to obtain a key target spot of the NSAIDs-induced liver and kidney disease, and verifying by using a molecular docking technology. Compared with a traditional method, the method has the advantages that firstly, the method does not depend on large-scale patient clinical data and a large number of animal or cell experiments, and ethical disputes in animal experiments and human body experiments are avoided; and secondly, the method can identify potential cross pathways and synergistic toxicity mechanisms when the compound causes various diseases, and is beneficial to more comprehensively evaluating the toxicity risk of the NSAIDs.

The present invention relates to a formulation in particular an oral formulation for the prophylaxis and treatment of TG2-related disorders like fibrosis in particular diabetic nephropathy and / or diabetic associated non-alcoholic steatohepatitis (NASH) and / or non-alcoholic steatohepatitis, and its use in the prophylaxis and / or treatment of fibrosis in particular nephropathy, NASH, idiopathic pulmonary fibrosis, and cystic fibrosis. Further, the present application relates also to the use of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate as hepatoprotectant, i.e. as hepatoprotective agent. In addition the present invention relates to a pharmaceutical composition comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate for use as hepatoprotective agent and for use in the protection of the liver against liver toxicity, the improvement of liver function, and / or in the prophylaxis or treatment of a liver disease or liver disorder.

The invention belongs to the technical field of biological medicine, and particularly relates to an extrahepatic targeting lipid nanoparticle composition and application thereof. The lipid nanoparticle composition is prepared from the following raw materials: SM1012, DSPC (Distearoyl Pyrrolidone), beta-sitosterol and DMG-PEG (Dimethyl Glycol-Polyethylene Glycol) The DSPC accounts for 20%-30% of the lipid nanoparticle composition in percentage by mole. The lipid nanoparticles can significantly change the in-vivo distribution behavior in different injection modes. Different from the characteristic that a large number of traditional lipid nanoparticles are enriched in the liver after being injected in different modes such as intramuscular injection, the lipid nanoparticles can effectively reduce targeted aggregation towards the liver after being injected in the same way, so that high-concentration retention and enrichment in a local injection area are realized, and the lipid nanoparticles have the advantages of high bioavailability and high bioavailability. The bioavailability of the medicine at a target part can be improved, the whole body exposure and the potential hepatotoxicity are reduced, and a better delivery strategy is provided for local precise administration.

This invention relates to a method for the rapid and large-scale preparation of liver organoids, and to methods for screening drugs related to liver diseases and screening drug in vitro toxicity using these methods. According to the above-described preparation method, liver organoids can be rapidly and massively prepared by continuously undergoing a three-dimensional differentiation process on the same microplate. The massively prepared liver organoids using the above-described method include hepatocytes (solid core part), cholangiocytes (cystic part), hepatic stellate cells, and Kupffer cells, possessing a cellular composition, structure, and function similar to actual liver tissue, and can stably proliferate in vitro. Furthermore, the in vitro drug toxicity screening method for liver organoids of this invention allows for the pre-screening of drugs that may have hepatotoxicity, shortening the time and cost of new drug development and improving its efficiency.

The invention discloses an in-vitro hepatotoxic drug screening method based on a high-throughput plug-in chip, and belongs to the technical field of plug-in chip drug toxicity screening. According to the method, a high-throughput plug-in chip is composed of a pore plate layer, a channel layer and a plug-in; every three holes form a chip unit, separation and material exchange between the pore plate layer and the channel layer are carried out through the porous membrane on the plug-in, and gravity flow is provided through the swing table; the chip hole pitch accords with the specification of a commercial pore plate, and is compatible with various analytical instruments. Through liver chip model construction, drug incubation testing and data processing analysis, efficient hepatotoxicity drug screening is realized. According to the invention, the human adult stem cell-derived liver organs are used for establishing the chip model, and the physiological correlation of the cells is strong; compared with a mouse model, human physiological liver parenchyma characteristics can be better simulated; the operation is simple and the consumed time is short. The method realizes high-efficiency and high-reproducibility drug screening, and plays a great role in the fields of basic research, transformation application and the like of preclinical tests of drugs.

The invention belongs to the field of biological medicines, and provides an application of acetoacetic acid and derivatives thereof in preparation of medicines for treating or relieving hepatotoxicity caused by antituberculosis medicines. The hepatocytes formed by differentiation of human induced pluripotent stem cells are verified, and hydrazine is a metabolite with the strongest toxicity, so that the content of acetoacetic acid in the metabolite in the cells is reduced. Acetoacetic acid is one of main ketone metabolites in the ketone metabolism process, and cells can convert acetoacetic acid into acetoacetyl coenzyme A through succinyl coenzyme A: 3-oxo acid coenzyme A transferase. According to the invention, the OXCT1 gene in the human induced pluripotent stem cell is knocked out through CRISPR-cas9 and the human induced pluripotent stem cell is differentiated into the hepatocyte, so that the knockout of the OXCT1 gene increases the content of acetoacetic acid and reduces hepatic differentiation cell death caused by hydrazine.