Protective effect of glycyrrhetinic acid against cantharidin-induced hepatotoxicity through reducing oxidative stress in mice

Background:Cantharidin(CTD)is a commonly used natural product with anticancer properties;however,it has significant adverse effects,particularly hepatotoxicity.Glycyrrhetinic acid(GA),the active component of licorice,shows potential hepatoprotective effects.The protective effects and mechanism of GA against CTD-induced hepatotoxicity are still unclear.Objective:This study aims to elucidate the effect and mechanism of GA on CTD-induced hepatotoxicity in mice experiments.Methods:Construction of CTD-induced hepatotoxicity models and oral gavage GA intervention for 14 d.The liver index,ALT,AST and LDH levels in the serum of the mice were examined;HE staining was performed to observe pathological changes in the liver.The MDA level and SOD activities in liver tissue were tested.Western blot was conducted to determine Keap1/Nrf2 signaling pathway-related protein expression.Results:The results showed that GA significantly reduced the levels of ALT,AST,and LDH in the serum,which were increased by CTD.Additionally,it also exerted a substantial inhibitory effect on the reduction of SOD activity and the elevation of malondialdehyde content in liver tissue.Notably,the phenomena of nuclear swelling,necrosis,and inflammatory infiltration of liver tissue were significantly attenuated following oral administration of GA in mice.Subsequent research has demonstrated that GA effectively suppressed the CTD-triggered upregulation of Keap1 while increasing the CTD-induced downregulation of Nrf2,HO-1,and NQO1.Conclusion:These findings suggested that GA may protect against CTD-induced hepatotoxicity in mice by exerting antioxidative stress through the Keap1/Nrf2 signaling pathway.

Magnesium cantharidate suppresses PP2A and ERK1/2 pathway to inhibit hepatocellular carcinoma cells

Background:Magnesium cantharidate(MC)is a protein phosphatase 2A(PP2A)inhibitor antitumor drug.However,its antitumor mechanism in hepatocellular carcinoma cell(HCC)remains unclear.Methods:PP2A lentiviral vector over expression strategy was utilized both in vivo and in vitro to explore the antitumor effect in MC and okadaic acid(OA).Tumor weight was detected in mice after MC and OA exposure.Cell proliferation,cell cycle,apoptosis rate,and western blotting were detected to explore the effects on MC and OA in human hepatocarcinoma SMMC-7721 cells.Results:In vivo results demonstrated that MC inhibited HCC progression while OA promoted tumor growth.In vitro results demonstrated that MC effectively inhibited the growth of SMMC-7721 cells by arresting the cell cycle at the G2/M phase with inhibiting Cdc25C and activating the phosphorylation of the Cdc2 protein.Flow cytometry results further showed that MC increased apoptosis.Furthermore,the expression of phosphorylated ERK1/2 was lower in the MC group but higher in the OA group.Molecular docking results showed that MC docked well with ERK1/2.Conclusions:MC inhibited HCC progression by suppressing the growth and activating the apoptosis of cancer cells and suppressing the expression of PP2A and ERK1/2.

Investigating the mechanism of action of Bu-Yang-Huan-Wu decoction in treating bleomycin-Induced pulmonary fibrosis through the epithelial-mesenchymal transition pathway

Background:To explore the effects and mechanisms of Bu-Yang-Huan-Wu Decoction on pulmonary fibrosis in mice.Methods:Forty-five C57BL/6J mice were randomly divided into three groups:Control,Model,and Bu-Yang-Huan-Wu Decoction.Pulmonary fibrosis was elicited in mice through a solitary intratracheal administration of 2.5 mg/kg bleomycin.For the control group,mice were given a solitary intratracheal administration of a comparable volume of PBS.Treatment began on the first day after the successful model establishment and lasted for 21 days.The survival rate and body weight of the mice were recorded daily,and on the 22nd day,bronchoalveolar lavage fluid was collected to determine total cells and total protein.The wet/dry weight ratio of lung tissue and hydroxyproline were measured.Lung tissue pathology was observed using hematoxylin and eosin staining and Masson staining.The mRNA expression of epithelial-mesenchymal transition-related proteins(E-cadherin and vimentin)was detected by RT-qPCR,and their protein expression was analyzed by western blot.Results:Compared to the model group,the Bu-Yang-Huan-Wu Decoction treatment notably enhanced both the survival rate and body weight in pulmonary fibrosis mice,significantly reduced lung tissue wet/dry weight ratio,total cells,and protein in bronchoalveolar lavage fluid,and hydroxyproline content.The pathological morphology of lung tissue was significantly improved,with increased expression of the epithelial cell marker E-cadherin mRNA and protein,and decreased expression of the mesenchymal cell marker vimentin mRNA and protein.Conclusion:Bu-Yang-Huan-Wu Decoction can improve the degree of bleomycin-induced pulmonary fibrosis in mice by inhibiting epithelial-mesenchymal transition.

The causes of adverse reactions in traditional Chinese medicine

With the increasingly widespread application of traditional Chinese medicine in clinical practice,the safety of traditional Chinese medicine has been given more attention.The occurrence of adverse drug reactions of traditional Chinese medicine will harm the health of patients,leading to a certain incidence rate and mortality rate,and serious adverse drug reactions of traditional Chinese medicine will lead to increased treatment costs of patients,bringing huge economic burden to patients and society[1-3].

Growth indices of seeds(maize and cowpea)grown in heavy metal contaminated soil treated with ginger extract

The consumption of maize and cowpea in Africa and developing countries is high,owing to the fact that they are readily available,coupled the with nutritional benefits they provide.Growth loss has been seen in crops cultivated on heavy metal polluted soils as a consequence of alterations in physiological and biochemical processes.This study was aimed at assessing the growth indices of seeds(maize and cowpea)grown on heavy metal contaminated soil treated with ginger extracts.The study adopted a Complete Randomized Design(CRD)in which growth indices of either maize or cowpea were examined from each crop type grown on soil without any pollutant or treatment and soils with metal pollutants;with or without treatment with ginger extracts in the individual experiments.Data were analyzed using ANOVA.The results showed that ginger extract induced oxidative stress on cowpea after 10 days of cultivation with root length significantly(P≤0.05)higher on the normal control-G-M and+L-G which recorded 7.60 and 7.3 cm respectively.Patterns of growth indices noticed after 30 and 40 days of cowpea cultivation were variable showing least growth in leaf development.Highest maize root(27.00 cm),shoot(8.85 cm)and leaf(25.25 cm)development were recorded in maize grown on soil without metal contamination but treated with ginger(+G-M-positive control)after days 10,40 and 40 after cultivation.It was observed that the soil contaminated with heavy metals affected the growth pattern of the crops thereby causing stunted growth,chlorosis,discoloration and wilting.It could be concluded that cowpea performed better in shoot of both treated and untreated soils even though the values were not significantly different from that of root and leaf while maize showed a decrease in shoot even though the values for root and leaf were not significantly different.

Glutathione peroxidase mimicry of diphenyl diselenide: Plausible contribution of proteins’ thiols

Organoseleniums are a class of compounds attracting attention across the globe owing to their Glutathione peroxidase(GPx)mimicry,which confers on them a strong antioxidant activity.Diphenyl diselenide(DPDS)is an Organoselenium whose GPx mimetic property has been suggested to rely on the oxidation of non-protein or protein thiols critical to the activities of some sulfhydryl enzymes.This study,therefore investigated the GPx mimic/antioxidant property of DPDS as well as the role of thiols of two key sulfhydryl enzymes,cerebral Na^(+)/K^(+)-ATPase(sodium pump)and hepatic delta-aminolevulinic acid dehydratase(δ-ALAD)in the GPx mimicry of DPDS.Albino Wistar rats were euthanized,and the liver and brain were removed and used to assay for the effect of DPDS on lipid peroxidation induced by two prooxidants[Fe2^(+)(10μM)and H2O2,(1 mM)]as well as the activities of the sulfhydryl enzymes.The results revealed that DPDS profoundly(P<0.05)counteracted Fe2^(+)and H2O2-induced lipid peroxidation in the rats’hepatic and cerebral tissues.Furthermore,the results of assay systems for lipid peroxidation and sodium pump revealed that DPDS inhibited Na^(+)/K^(+)-ATPase and lipid peroxidation in the brain tissue homogenates in the same reaction system.A similar result was obtained in the assay system for lipid peroxidation and hepaticδ-ALAD as DPDS simultaneously inhibited the enzyme’s activity and lipid peroxidation.This suggests that the GPx mimetic property of DPDS may be linked to the enzymes’loss of activity,which further validates the suggestions that the enzymes’inhibition,as well as the antioxidant action of DPDS,rely on the oxidation of critical thiols of the enzymes.However,the GPx mimicry of DPDS should be investigated in the presence of thiol-blocking or oxidizing agents in biological systems in order to further ascertain the role of protein thiols.

Ethanolic extract of Abrus precatorius leaves protected against mercury chloride-induced hepatocellular damage and cerebral Na+/K+-ATPase dysfunction in wistar rats

Plants are sources of medicinal compounds,and they play a crucial role in human health maintenance.Abrus precatorius is one of the important medicinal plants that have been alleged for their medicinal properties.This research unraveled the pharmacological effect of ethanolic extract of Abrus precatorius on lipid peroxidation,liver parameters,and Na^(+)/K^(+)-ATPase activity in HgCl_(2) treated wistar rats.Twenty-four(24)albino wistar rats weighing between 150-200 g were distributed into four groups of 6 animals each.Group A(control)received normal saline(0.9% NaCl),group B received 400 mg/kg of the extract only,group C received 4 mg/kg HgCl_(2) only,and group D received 400 mg/kg of extract+4 mg/kg of HgCl_(2).The treatment lasted for two weeks,and the animals were sacrificed on the 15th day.The blood,brains and livers were collected and used for assay of lipid peroxidation,liver function,and sodium pump activity.The results of liver function test revealed an elevated(P<0.05)level of serum aspartate transaminase,alanine transaminase,alkaline phosphatase,and total bilirubin in the group that received HgCl_(2) only(group C)when compared with the normal control(group A)that received normal saline only.However,the administration of extract in group D led to a marked(P<0.05)reduction in the activities of these enzymes and the level of total bilirubin when compared to the negative control(group C).On the contrary,HgCl_(2) caused a significant(P<0.05)reduction in serum total protein and albumin levels,but the extract reversed the effect of HgCl_(2) by elevating their concentrations.Nonetheless,the effect elicited by this extract is comparable to group A which received normal saline.Moreso,the result of lipid peroxidation revealed that HgCl_(2) treatment caused a marked(P<0.05)increase in the formation of lipid peroxidation adducts in both liver and brain homogenates in group C.On the contrary,administration of Abrus precatorius extract profoundly(P<0.05)inhibited HgCl_(2)-induced lipid peroxidation in group D.In addition,HgCl_(2) inhibited the activity of cerebral Na^(+)/K^(+)-ATPase,but the extract restored normalcy by increasing the activity of the enzyme in group D.Consequently,the results obtained justify the traditional use of Abrus precatorius and suggest that Abrus precatorius leaves may be used for management of liver diseases,oxidative stress-linked diseases and some neurodegenerative ailments.

Heavy metals and health risk analysis of arable farmlands in selected local government areas of Taraba State,Nigeria

The soil environment is a reservoir of nutrients as well as pollutants,and because of this,most of our food items are ladened with lots of pollutants ranging from fertilizers,pesticides,herbicides to heavy metals(HM).The consumption of these contaminated food items has serious implication on the health and economic status of the populace.These pollutants have also been implicated in causing several problems to plants.This study investigated heavy metals and health risk analysis of arable farmlands in selected Local Government Areas(Donga,Ussa and Takum)of Taraba state Nigeria.Samples obtained were processed and the concentration of following heavy metals(Pb,Cd,Cr,Hg,and As)were determined using Atomic Absorption Spectrophotometry(AAS).The results showed that Chromium had a very high concentration across all the study areas with values ranging from 1.40mg/kg to 2.30 mg/kg.The concentration of Cadmium and Arsenic were moderate,with values ranging from 0.03mg/kg to 0.08mg/kg while Lead and Mercury had the lowest concentration of less than 0.03mg/kg across the three LGAs respectively.The following ecological and health risk assessments parameters;Target Cancer Risk or Target Hazard Quotient(THQ),Hazard Index(HI)and Estimated Daily Intake(EDI)were determined to assess the carcinogenic health risks by consuming produce from such farmlands.Ussa LGA recorded the highest concentration of heavy metals,with the highest health risk index followed by Takum whereas Donga had the lowest risk factors from the analysis.The study showed bioaccumulation of toxicants from the soil to crops and grazing plants across the study areas which was as a result of chemical farming that polluted and contaminated the soil,thus posing risk to the populace.

Assessment of d ifferent f ormalin c oncentrations on the h istochemical s taining of l iver,k idneys and l ungs of Wistar r ats

Background:Formaldehyde is a chemical substance used to preserve the biochemical and physiological components of a tissue by preventing autolysis and putrefaction,leaving the tissue in a life-like manner.Objective:This study aims to assess the effect of formalin concentrations on the histochemical staining in liver,kidneys and lungs of Wistar rats.Methods:A total of ten(10)Wistar rats were purchased and allowed to acclimatize for a period of 2 weeks in plastic cages with iron netting at the Animal House facility,Babcock University.The animals were placed on standard rat feeds and water ad-libitum.The rats were randomly sacrificed by cervical dislocation,following mild anaesthesia using chloroform inhalation.For histological examination,the liver,lungs,and kidneys of Wistar rats were removed and preserved in neutral buffered formalin at 2%,4%,6%,8%,and 10%concentrations.Sections were stained in Haematoxylin and Eosin(Vector Laboratories,Inc.Newark,US).The quality of the nuclei,cytoplasm and cell membrane were graded on a scale of 1(poor)to 5(excellent).Results:Six percent(6%)formalin was observed to produce excellent results in liver tissues with a total grade of sixteen(16).10%formalin produced excellent results in lung tissues with a total grade or nineteen(19).Interestingly,2%,6%and 10%formalin concentrations produced excellently results in kidney tissues with the highest total grade fourteen(14).Conclusion:This study concludes that 6%formalin produced better section and staining qualities more than the commonly used 10%formalin according to the observations from the stained sections.This implies that the concentration of formalin affects the histochemical staining in liver,kidneys and lungs of Wistar rats.

Antinephrotoxic and antihyperlipidaemic activities of Cucurbita maxima leaf supplemented diets in stz-induced diabetic rats

Background:Cucurbita maxima plant materials are frequently used to manage a number of disorders,according to previous studies.Objective:The goal of the present report was to look into further possible effects of this plant on kidney disorder in rats brought on by diabetes as well as the related abnormalities in lipid metabolism.Methods:To assess the ameliorative effect of the plant,streptozotocin(STZ)(45 mg/kg/day)was given as a single dosage to cause type 1 diabetes.After then,diabetic rats received supplemented diets of Cucurbita maxima for four weeks at 5%,10%,15%and 20%ad libidium.However,in another experiment to evaluate the preventive capacity of Cucurbita maxima,the STZ-induction came at the end of four weeks supplementation.Blood and kidney tissues were obtained at the end of the treatments and investigated.Consequently,the analysis of kidney function and lipid profile was made using serum obtained from the blood sample.Histological change in kidney was also observed using haematoxylin and eosin stain Results:Our findings demonstrated that Cucurbita maxima drastically(P<0.05)decreased the elevated kidney indicators such as urea and creatinine in the blood,and restored the electrolytes and lipid profiles anomalies as compared to the normal control.However,the alteration of biochemical parameters in the STZ-induced diabetic control remained unchanged throughout as compared to the normal control.The above mentioned biochemical changes that took place in kidney tissues were further corroborated by histological alterations.Conclusion:The results suggest that Cucurbita maxima leaves supplemented diets reversed STZ-induced renal disorder and abnormal lipid metabolism,and that these effects may be mediated by interacting with multiple receptors to raise the levels of antioxidant enzymes in the system.

Occupational exposure to flour dust among bakery workers:prevalence,potential hazards and promising interventions

Occupational exposure to flour dust within bakery environments presents significant health hazards to bakery personnel.Flour dust,generated as a byproduct during baking,becomes airborne during the baking process,thus constituting a respiratory threat.Adverse health consequences include respiratory diseases,skin irritation,allergic reactions,and potential long-term health impacts.Data indicates that a broad segment of bakery workers encounters exposure to flour dust,with specific subgroups,such as bakers and dough mixers,being particularly susceptible.Contributing factors to this exposure encompass insufficient ventilation and a lack of awareness.It is vital to assess exposure levels through air quality monitoring and health surveillance.Efficient interventions encompass engineering solutions(e.g.,ventilation systems,dust extraction),administrative measures(including training and the use of personal protective equipment),and the implementation of occupational health and safety programs.Collaborative efforts with healthcare professionals and regulatory authorities are paramount for achieving success.Case studies underscore the effectiveness of such interventions,resulting in improved worker health,thus underscoring the advantages of protective measures.Challenges in this endeavor include industry resistance to change,financial considerations,and issues related to compliance.Future recommendations entail further research,policy enhancements,and the involvement of industry stakeholders and labor unions in advocating for worker safety.

Quantity:a parameter deciding various health hazards

Plants are vital to the survival of life on e arth and have enormous implications for both the environment and human well-being.Plants carr y both medicinal and toxic properties.The plants were used by people traditionally for medicinal purposes.But people were not aware of the concentration of the dose s.So,excessive quantity of dose s may lead to severe toxic effects on the human body.This topic discusses the potential hazards of toxic plants on human health.There are many plants around the world that can cause adverse effects,ranging from mild irritation to severe organ damage or death.This review focuses on the plants which are available locally used as medicines carrying toxic properties too.It is essential to learn to recognize them and avoid touching or ingesting them.If exposure does occur,prompt medical attention is necessary.Understanding the risks associated with toxic plants can help individuals take the necessary precautions to protect their health.

Studies on Heavy Metals Levels in Hepatic Tissues of Cat Fishes(Clarias gariepinus)from River Ibi,Donga and Gindin-Dorowa in Taraba State Nigeria,in Relation to key Enzyme of heme Biosynthetic Pathway

Fishes are excellent markers of the extent of pollution from heavy metals in aquatic environments given that they are found at various levels of the food chain.This study aimed to investigate the bioaccumulation of heavy metals(Zn,Pb,Cd,As,and Hg)as well as the activity of delta-aminolevulinic acid dehydratase(δ-ALA-D)in the livers of cat fishes(Clarias gariepinus)collected from three rivers(Donga,Ibi and Gindin-Dorowa)in Taraba State,Nigeria.The concentrations of heavy metals in the liver tissues were determined using an atomic absorption spectrophotometer in accordance with the method of AOAC(2019),while theδ-ALA-D activity was assayed using the method of Sassa(1982).Results revealed that only Zn and As were present in the liver samples from the three rivers.Pb was found only in the liver from Gindin-Dorowa at the concentration of 0.0012mg/kg which is not significant(P<0.05)when compared with other locations,while Hg and Cd were absent in all the liver samples.The liver sample from Gindin-Dorowa had the highest concentration of Zn(4.2500 mg/kg),followed by Ibi(3.2067 mg/kg),and Donga having the least(2.5500 mg/kg),which were all substantially(P<0.05)different from one another.However,there was no significant(P<0.05)difference in the As composition of liver from Donga(0.0013 mg/kg),Ibi(0.0012 mg/kg)and Gindin-Dorowa(0.0010 mg/kg).The result ofδ-ALA-D activity showed that the highest enzymatic activity was found in the liver sample from Donga which has the least Zn and no Pb content,followed by Ibi sample.This validates the report that heavy metals impairδ-ALA-D activity.Nonetheless,the concentrations of all metals in fish livers from all regions do not exceed the acceptable limits set by international law,making them safe for human consumption and possibly not having a negative impact on public health.Since there is little or no industrial activity in the studied locations,these levels may be consequent to low anthropogenic inputs.The current situation should be safeguarded to prevent pollution of the river’s aquatic biota in the near future,and more appropriate steps should be made to guarantee higher fish quality and life in the rivers.

The application of omics technologies to toxicology

The application of omics technologies,including genomics,transcriptomics,proteomics and metabolomics,has the potential to revolutionize toxicology by providing a more comprehensive understanding of the molecular mechanisms of toxicity,identifying potential biomarkers of exposure or effect,and enabling personalized risk assessments for individuals.Each omics approach has its own challenges,including data analysis and interpretation,but the integration of multiple omics approaches can provide a more comprehensive understanding of toxicity.The use of omics technologies for personalized risk assessments can inform targeted interventions and improve public health outcomes.While challenges remain,the potential benefits of omics technologies in toxicology make it an exciting area of research for the future.

Microplastic pollution in the Indian Ocean: Passageways and the contamination of the open ocean and its marine environment

Microplastics(MPs)are man-made litter receiving current conversation of interest as a silent pollutant to Earth.Its impact is high on the coastal waters,sediment and organisms of the marine environment.It is a pertinent requirement to investigate the microplastic MP contamination in the marine environment of the Asian region aiming at the world’s 3rd largest ocean,the Indian Ocean.Among the different samples,Indian Ocean water and deep-sea sediment samples have mostly been investigated covering the Southwestern Sumatran region(Eastern Indian Ocean)which is a well-known domestic and industrial shipping route.Majority of the tested samples were in the form of granules,fibers and fragments of 100-500μm and 38-6,330μm in size range respectively in deep-sea sediment samples and in ocean water samples.Further,the prominent MPs types were PVC(polyvinyl chloride),PP(polypropylene)synthetic micro debris,Poly methyl methacrylate PMMA plastic micro debris,PTFE(polytetrafluoroethylene),and nylon.Floating plastic debris has also been found on surface ocean waters in the Eastern Indian Oceanic region as an emergent floating litter.Its size range and the percentage abundance were documented as 0.5-5 mm and 50%respectively.Moreover,the Western Indian Oceanic region has reported the highest percentage abundance of MPs in ocean waters(10.48%).These MPs were assumed to derive from fiber or fishing line material,regional fishery activities and the sewage disposal debris of tourist-based coastline anthropogenic activities.The polymer-specific sources that release this potential pollutant were not yet accurately discovered.This review article elaborates on the topic by reviewing the MPs’pervasiveness,identifying different passageways and sources of discharging MPs to the Indian Ocean and finally the ecological and socio economic risks of the matter.Thus,it may highlight the knowledge gaps which more research studies should be focused on.

Advances in toxicological studies of Radix Phytolaccae

Radix Phytolaccae is the dried root of Phytolacca acinosa Roxb or P.ameri-cana L,which is commonly used as a traditional Chinese medicine to treat diseases like cirrhotic ascites,hepatitis B,nephrotic syndrome,psoriasis,etc.However,there is no exact basis for its clinical application safety.In this paper,the toxic effects and mechanism of Saponin A(EsA),the main component of Radix Phytolaccae,were summarized by searching the results and reports of toxicology related to the plant from 1991 to 2023 on CNKI and pubmed,aiming to provide reference for the toxicological research and future research direction of Radix Phytolaccae,so that Radix Phytolaccae can be safely and effectively used in clinical practice.

Investigation of heavy metals and lipid peroxidation level in the muscles of Clarias gariepinus from IBI,Gindin-Dorowa and D onga community rivers in Taraba State,Nigeria

Heavy metals have harmful effects on human health,and exposure to these metals has been increased by industrial and anthropogenic activities and modern industrialization.Heavy metals content of the liver tissues was determine d using Atomic Absorption Spectrophotometer method,while lipid peroxidation was carried out.Heavy metals analyzed include;lead(Pb),cadmium(Cd),zinc(Zn),Arsenic(As),and Mercury(Hg).The findings revealed that the heavy metal Zinc(Zn)has high concentrations in the muscles of the fish species,the concentration of this heavy metal Zinc is high in River Gindin Dorowa th a n in River Ibi and River Donga shows less concentration of this heavy metal though it’s above WHO permissible limits.Results revealed that only Zn and Cd were present in the muscle from the three rivers.Pb was found only in the liver from Gindin-Dorowa at the concentration of 0.017 mg/kg,which is not significant(P<0.05)when compared with other locations,while Hg and As were absent in all the muscle samples.The highest concentration of Zn was found in the muscle sample from Gindin-Dorowa(7.450 mg/kg)followed by Ibi(6.16 mg/kg)and the least being Donga(4.365 mg/kg)which are significantly(P<0.05)different from one another.However,there was no significant(P<0.05)difference among the Cd composition of muscle from Gindin-Dorowa(0.025 mg/kg),Donga(0.024 mg/kg)and Ibi(0.015 mg/kg),respectively.The TBA was found in the hepatic tissue sample from Gidin-Dorowa,which has the highest Zn,Cd and no Pb content,followed by Ibi and then the Donga sample.This suggests that there is a positive relationship between heavy metals and the effect of TBA on the hepatic tissues,justifying the fact that heavy metals affect the hepatic tissues of fish,while on the cerebral tissue.In conclusion,it revealed that there is a negative relation between heavy metals and the effect of TBA on the cerebral tissues to protect or save aquatic habitat s of fish quality and aquatic life.

Combating mitochondrial toxicity: looking at the past and where to go

Mitochondria are the main sources of intracellular energy and reactive oxygen species(ROS),which play an important role in the regulation of cell survival and death under pathological conditions.Mitochondria are important targets of drug toxicity[1].Some antiviral drugs,antitumor drugs and antibiotics can significantly induce mitochondrial damage in target organs such as the liver and heart[2].Drug-induced mitochondrial damage may involve multiple pathways and mechanisms.

Redox and metabolic regulation of epigenetic modifications:an emerging toxic action mechanism

Epigenetic modifications modulate conformational structure of chromatin and consequently gene expression by enzyme-mediated chemical modifications of DNA and histones.The activities of epigenetic modifying enzymes depend on many co-substrates and cofactors,such as 2-oxoglutarate(2-OG),iron,S-adenosylmethionine(SAM),nicotinamide adenine dinucleotide(NAD+),flavin adenine dinucleotide(FAD),and acetyl-CoA.These factors are inter-connecting molecules that integrate cellular nutrient metabolism and redox homeostasis,two key regulators of cell proliferation,cell survival,and cell functions.Dysregulation of such delicate regulatory network has been implicated in many pathological conditions and also been increasingly recognized as an emerging mechanism responsible for environmental pollutant-induced adverse effects.In this review,we first summarize DNA and histone modifying enzymes and their essential factors,then discuss the metabolic sources and the redox regulatory roles of these enzymatic factors,and finally elaborate the mechanisms of how targeting such factors by environmental pollutants influences epigenetic regulation and perturbs cellular functions.

Study on hepatotoxicity of Aconitum brachypodum based on network pharmacology and molecular docking

Objective:To explore the potential mechanism of hepatotoxicity induced by Aconitum brachypodum through network toxicology.Methods:The active components and targets of Aconitum brachypodum were identified and screened by CNKI,PubChem database,Swiss Target Prediction database.Genecards,pharmGKB and DisGeNET databases were used to collect hepatotoxicity related targets.The intersection targets were obtained by matching the active component targets with the hepatotoxic targets of Aconitum brachypodum.Cytoscape software was used to construct the"Aconitum brachypodum-potential active components-potential targets-hepatotoxicity"network.The STRING database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted by R software.The toxic components in Aconitum brachypodum were docked with the core targets.Results:In this study,26 chemical components were screened via SwissADME,297 targets for the active components of Aconitum brachypodum were obtained.There were 1,096 hepatotoxicity-related targets,73 potential targets for hepatotoxicity caused by Aconitum brachypodum,and 15 potential active components,among which Penduline,Songoramine,Sitosterol,Daucosterol and Bullatine A were the key active components for hepatotoxicity caused by Aconitum brachypodum,and signal transducer and activator of transcription 3(STAT3),epidermal growth factor receptor(EGFR),mitogen-activated protein kinase 8(MAPK8)and tyrosine-protein kinase JAK2(JAK2)were the potential targets for hepatotoxicity caused by Aconitum brachypodum.There were 1,133 GO entries(P<0.05),including 1,045 entries of biological process(BP),19 entries of cellular component(CC),and 69 entries of molecular function(MF).KEGG enrichment analysis revealed 115 pathways(P<0.05),of which EGFR tyrosine kinase inhibitor resistance,hypoxia-inducible factor 1(HIF-1)signaling pathway,PI3K-Akt signaling pathway,calcium signaling pathway,T helper 17(Th17)cell differentiation was strongly correlated with the hepatotoxicity caused by Aconitum brachypodum.Molecular docking results showed that the binding activity was good.Conclusion:Through network toxicology analysis,it was found that the active ingredients in Aconitum brachypodum may act on multiple targets and signaling pathways,thereby participating in the activation of an excessive inflammatory response,oxidative stress,apoptosis and other pathways on the whole,thus resulting in hepatotoxicity.