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Radioprotective Potencies of Allium Cepa Extract (ACE) against Radiation-Induced hepatoxicity in Wistar Rats

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International Journal of Medical Physics, Clinical Engineering and Radiation Oncology 2023年第3期12卷 59-83页

作者： Sylvester Kelechi Kenneth Okeke Francisca Nneka Agwu Kenneth Kalu Attah Okwudili Joseph Deparrtment of Radiation and Clinical Oncology University of Nigeria Teaching Hospital Enugu Nigeria Department of Physics and Astronomy University of Nigeria Nsukka Nigeria Department of Medical Radiography Faculty of Health Science University of Nigeria Enugu Campus Enugu Nigeria

Background and Purpose: All types of ionizing radiations generate ions which can lead to the formation of free radicals and reactive oxygen species (ROS). Excess production of free radicals or decrease in antioxidants level leads to oxidative stress. It is a harmful process that induces damage to cell structures, lipids, proteins, RNA and DNA which leads to a number of diseases. The aim of this study is to examine the effect of plant extract (Allium Cepa Extract (ACE)) on the kidney of wistar rats exposed to radiation using and assaying some biochemical enzymes. Material and Method: 60 wistar rats weighing 170 ± 20 g were equally divided into six groups for the study. Group 1 (control): neither received ACE nor irradiation. Group 2 (ACE): received 1000 mg/Kg b.wt of ACE. Group 3 (4 Gy-Irradiated): were exposed to 4 Gy TBI on day 14. Group 4 (6 Gy-Irradiated): were exposed to 6 Gy TBI on day 14. Group 5 (ACE + 4 Gy): were treated with 1000 mg/Kg b.wt of ACE once daily for twenty-eight days but exposed to 4 Gy TBI on day 14. Group 6 (ACE + 6 Gy): were treated with 1000 mg/Kg b.wt of ACE once daily for twenty-eight days but exposed to 6 Gy TBI on day 14. All the groups received distilled water and feed ad libitum during the acclimatization and experimental periods. Four animals in each group were sacrificed 24 h after irradiation and the 4 remaining animals were sacrificed on day 29 for biochemical assay and histopathological evaluation, the statistical analysis was done using one-way analysis of variance (ANOVA) on the data editor SPSS version 28. Results: From the biochemical enzymes, the level of Malondialdehyde (MDA) in group 2 when compared to group 1 was almost the same, which was not statically significant with (p > 0.05), but groups 3 and 4 show a significant increase in the level of MDA with (p 0.05). The other enzymes like SOD, CAT, GST, and GSH followed suit. Conclusion: From the results it is a clear indication that Allium Cepa E

关键词： Allium Cepa Winstar RAT MDA SOD hepatoxicity

Profiling biotoxicities of hexafluoropropylene oxide trimer acid with human embryonic stem cell-based assays

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Journal of Environmental Sciences 2022年第6期34卷 34-42页

作者： Shengxian Liang Guoqiang Liang Yue Zhang Xiufang Zhang Li Zhong Institute of Life Sciences and Green Development College of Life SciencesHebei UniversityBaoding 071000China Western University of Health Sciences PomonaCalifornia 91766USA

Hexafluoropropylene oxide trimer acid(HFPO-TA), an emerging replacement of perfluorooctanoic acid(PFOA), has recently been reported to be a potential environmental contaminant.Due to the similar structure to PFOA, HFPO-TA may cause comparable adverse effects on human health. Therefore, evaluating the toxic profiles of HFPO-TA has become an urgent task.In this study, we investigated the cytotoxicity and hepatoxicity of HFPO-TA using human embryonic stem cell(h ESC)-based assays. Results showed that HFPO-TA reduced h ESCs’ viability in a dose dependent manner, and the calculated IC50 for 24, 48 and 72 hr were 222.8,167.4, and 80.6 μmol/L, respectively. Significant intracellular ROS accumulation and mitochondrion membrane potential reduction were detected with HFPO-TA exposure, and increased apoptotic/necrotic cells were also observed in high dose of HFPO-TA treated group.Moreover, HFPO-TA at noncytotoxic concentrations also significantly impaired the functions of induced hepatocytes by diminishing cell glycogen storage ability and deregulating specific functional genes. Transcriptome sequencing analysis identified a set of hepatic associated biological processes responding to HFPO-TA exposure. PPAR was the most significantly enriched pathway. Genes including FGA, FGB, FGG, AHSG, HRG, ITIH2, ALB were characterized as hub genes by cyto Hubba plug-in. These data indicated that HFPO-TA is a potential hepatotoxicant, and may not be a safe replacement for PFOA.

关键词： Hexafluoropropylene oxide trimer acid(HFPO-TA) Stem cell toxicology hepatoxicity Transcriptional analysis

Update on herbal and dietary supplement-induced liver injury:current gaps and future directions

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Hepatobiliary Surgery and Nutrition 2023年第5期12卷 752-755页

作者： Sabine Weber Alexander L.Gerbes Department of Medicine II University HospitalLMU MunichMunichGermany

Drug-induced liver injury(DILI)is a rare but potentially life-threatening condition,which accounts for the majority of acute liver failure cases in the US and EU.Unlike direct hepatoxicity,which is mainly caused by acetaminophen,idiosyncratic DILI is unpredictable and occurs unrelated to the dose or frequency of the medication.Interestingly,DILI cannot only be caused by a large variety of prescription drugs,but also by herbal and dietary supplements(HDS).While HDS-DILI has already played a role in Asian countries like China or Korea for a long time,there is also an increasing incidence of HDS-DILI in countries with formerly less HDS-DILI cases such as the US,presumably due to a rising usage of those remedies(1).

关键词： Herbal and dietary supplements(HDS) liver injury hepatoxicity autoimmune liver diseases

Drug-induced liver injury: Do we know everything?

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World Journal of Hepatology 2017年第10期9卷 491-502页

作者： Tamara Alempijevic Simon Zec Tomica Milosavljevic University of Belgrade School of Medicine Clinical Center of Serbia Clinic for Gastroenterology and Hepatology

Interest in drug-induced liver injury(DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. Clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. The consumption of unregulated herbal and dietary supplements has introduced new challenges in epidemiological assessment and clinician management. As such, numerous registries have been created, including the United States Drug-Induced Liver Injury Network, to further our understanding of all aspects of DILI. The launch of Liver Tox and other online hepatotoxicity resources has increased our awareness of DILI. In 2013, the first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of Gastroenterology, and along with the identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have come to define the current state of the art, however, gaps in our knowledge still undoubtedly remain.

关键词：尖锐的肝失败导致药的肝损害 hepatoxicity Acetaminophen 毒性 Cholestatic 损害肝活体检视 Pharmacoepidemiology 草药导致肝损害 Hys 法律

Hepatoprotective and immunomodulatory properties of aqueous extract of Curcuma longa in carbon tetra chloride intoxicated Swiss albino mice

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Asian Pacific Journal of Tropical Biomedicine 2011年第3期1卷 193-199页

作者： Mahuya Sengupta Gauri Dutta Sharma Biswajit Chakraborty Department of Biotechnology Assam University Department of Life Science Assam University

Objective:To evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl_4 intoxicated Swiss albino mice.Methods:first group of mice(n=5) received CCl_4 treatment at a dose of 0.5 mL/kg bw(i.p.) for 7 days.Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for IS days.The third group was given both the turmeric extract(for 15 days,orally) and CCl_4(for last 7 days,i.p.).The fourth group was kept as a control.To study the liver function,the transaminase enzymes(SGOT and SGPT) and bilirubin level were measured in the serum of respective groups.For assaying the immunotherapeutic action of Curcuma longa(C.longa),non specific host response parameters like morphological alteration,phagocytosis,nitric oxide release,myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups.Results:The result of present study suggested that CCl_4 administration increased the level of SCOT and SGPT and bilirubin level in serum.However,the aqueous extract of turmeric reduced the level of SGOT, SCFT and bilirubin in CCl_4 intoxicated mice.Apart from damaging the liver system,CCl_4 also reduced non specific host response parameters like morphological alteration,phagocytosis, nitric oxide release,myeloperoxidase release and intracellular killing capacity of peritoneal macrophages.Administration of aqueous extract of C.longa offered significant protection from these damaging actions of CCl_4 on the non specific host response in the peritoneal macrophages of CCl_4 intoxicated mice.Conclusions:In conclusion,the present study suggests that C.longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.

关键词： Immune system Hepatotoxicity Curcuma longa Immunotherapeutic agents Hepatoprotectivity Turmeric rhizome hepatoxicity Transaminase enzyme Liver function Bilirubin Nitric oxide Morphological alteration

Analysis of the metabolic mechanism in Cantharidin-induced hepatotoxicity in LO2 cells using lipidomics analysis

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Asian Toxicology Tesearch 2021年第2期3卷 14-24页

作者： Jian-Yong Zhang Fang Liu Tian-Mu He Qi-Yi Wang Yan Zhang Xiao-Yan Yuan Xiao-Fei Li Can-Can Duan Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical UniversityZunyi 563000China.2Department of PharmacyZunyi Medical UniversityZunyiGuizhou 563000China.3School of Basic Medical SciencesZunyi Medical UniversityZunyi 563000China.

Background:Cantharidin is a major active compound from Banmao(Mylabris).Cantharidin has obvious anticancer activity.However,its clinical application is limited due to serious hepatotoxicity.Methods:To evaluate the toxicity of human liver LO2 cells exposed to cantharidin by lipidomics.After exposing LO2 cells to different doses of cantharidin,the metabolites in LO2 cells were analyzed by nontargeted lipidomics based on liquid chromatography-mass spectrometry.Partial least-squares discriminant analysis and orthogonal partial least-squares discriminant analysis were used to screen differentially expressed metabolites,and then the main metabolic pathways were analyzed.Results:Pattern recognition analysis showed that the lipid metabolite profiles were changed significantly after cantharidin treatment,and 39 differential lipid metabolites were found.Additional analysis showed that these metabolites could mainly involve the metabolic pathways of triglyceride and acylcarnitine for cantharidin toxicity to LO2 cells.Conclusion:Cantharidin has obvious toxic effects on LO2 cells from the perspective of lipid metabolism.Moreover,the LO2 cytotoxicity induced by cantharidin is mainly related to the disorder of triglyceride and acylcarnitine metabolism.It can provide a scientific basis for cantharidin-induced hepatotoxicity.

关键词： hepatoxicity Cantharidin LC-MS Lipidomics