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

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) while group 5 and 6 showed no significant increase in MAD 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 Extract can ameliorate the effect of radiation induced disease.

Cytochrome P450 enzymes mediated by DNA methylation is involved in deoxynivalenol-induced hepatoxicity in piglets

Deoxynivalenol(DON)is an inevitable contaminant in animal feed and can lead to liver damage,then decreasing appetite and causing growth retardation in piglets.Although many molecular mechanisms are related to hepatoxicity caused by DON,few studies have been done on cytochrome P450(CYP450)enzymes and DNA methylation.To explore the role of CYP450 enzymes and DNA methylation in DONinduced liver injury,male piglets were fed a control diet,or diet containing 1.0 or 3.0 mg/kg DON for 4 weeks.DON significantly raised the activity of aspartate aminotransferase(AST),alanine aminotransferase(ALT),and glutamyl transpeptidase(GGT)(P<0.01),leading to liver injury.In vivo study found that DON exposure increased the expression of CYP450 enzymes(such as CYP1A1,CYP2E1,CYP3A29)(P<0.05),and disturbed the expression of nicotinamide N-methyltransferase(NNMT),galanin-like peptide(GALP)and insulin-like growth factor 1(IGF-1)(P<0.05),in which DNA methylation affected the expression of these genes.In vitro study(human normal hepatocytes L02)further proved that DON elevated the expression of CYP1A1,CYP2E1 and CYP3A4(P<0.05),and inhibited cell growth in a dose-dependent manner,resulting in cell necrosis.More importantly,knockdown of CYP1A1 or CYP2E1 could alleviate DON-induced growth inhibition by promoting IGF-1 expression.Taken together,increased CYP450 enzymes expression was one of the mechanisms of hepatoxicity and growth inhibition induced by DON,suggesting that the decrease of CYP450 enzymes can antagonize the hepatoxicity in animals,which provides some value for animal feed safety.

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

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.

Drug-induced liver injury: Do we know everything?

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.

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

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.

HepaTox:促进中国药物性肝损伤临床和转化研究的专业网络平台

药物性肝损伤（DILI）是最重要的药源性疾病之一,也成为上市前药物注册失败、上市后增加警示以及撤市的主要原因。由于可引起肝损伤的药物种类繁多,且同一种药物在不同个体中可出现不同的临床损伤类型,因此,其发生多具不可预测性。

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

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.

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

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).