{"title":"Comprehensive Analysis of Epigenetic Associated Genes on Differential Gene Expression and Prognosis in Hepatocellular Carcinoma.","authors":"Cong Li, Jing Ding, Jianmin Mei","doi":"10.1615/jenvironpatholtoxicoloncol.2021039641","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039641","url":null,"abstract":"BACKGROUND Early detection of hepatocellular carcinoma (HCC) is significantly effective in clinical management. This study aimed to identify potential HCC biomarkers. METHODS Analysis of expression profiles in HCC clinical samples downloaded from the cancer genome atlas (TCGA) and the gene expression omnibus (GEO) datasets was performed to identify differentially expressed genes (DEGs) using R packages. The epigenetic differentially expressed genes (epiDEGs) were obtained after intersections of genes between DEGs and epigenetic factors (EFs). The biological functions of epiDEGs were annotated by gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Protein-protein interaction and expression correlation were performed to investigate the interactions among epiDEGs by the STRING online tool and R packages. The epiDEGs associated with overall survival (OS) were identified as patient prognosis using the Cox regression analysis. The levels of gene expression were validated by RT-qPCR and Western blot between HCC cell lines, (HepG2, and Huh-7) and normal cell lines (THLE-2). RESULTS Thirty-five epiDEGs were obtained, including 25 upregulated genes and 10 downregulated genes. Functional enrichment and PPI analysis indicated the development of HCC is a complicated process involving various genes and proteins. Survival analysis showed nine epiDEGs associated with the OS of patients and these might be the independent prognostic biomarkers for HCC. The expressions of most epiDEGs were significantly higher in HCC patients with stage II and III compared with stage I. Furthermore, the expression of these epiDEGs between HCC cell lines with normal cell lines was shown to be consistent with the TCGA and GEO datasets except PBK. CONCLUSIONS Eight hub epiDEGs, including EZH2, CDK1, CENPA, RAD54L, HELLS, HJURP, AURKA, and AURKB, were associated with the overall survival of HCC patients and could be potential biomarkers to predict prognosis.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"69 1","pages":"27-43"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83803226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sobia Nida, Hemalatha Srinivisan, A. Pandurangan, M. Waseem
{"title":"Mechanistic Episodes on SARS-CoV-2-Mediated Neurological Manifestations and Their Possible Therapeutic Interventions.","authors":"Sobia Nida, Hemalatha Srinivisan, A. Pandurangan, M. Waseem","doi":"10.1615/jenvironpatholtoxicoloncol.2021040128","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021040128","url":null,"abstract":"Recently, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been critically recognized and spread rapidly on this planet. Considerable recognition of SARS-CoV-2 has been known with a range of viruses that are more capable to cause diseases in avian and mammals including humans. The virus was found as a main culprit for major defects in respiratory system and thereby caused severe acute respiratory syndrome disease. This has led to depict the mortality in human population. Nevertheless, compromised reports on SARS-CoV-2 has also shown neurological complications in both central nervous system (CNS) and peripheral nervous system (PNS). This virus has notified with neurological defects as stroke, encephalopathy, cerebral edema, erythema, seizures, meningitis, ischemic, ageusia, loss of smell, myalgia and Guillain Barre Syndrome. In this review, we focused on COVID-19 mediated neurodegeneration and its mechanistic episodes on affected patients. We also discuss the possible available therapeutic interventions with clinically investigated drugs against COVID-19 mediated neurological impairment in patients and experimental in vitro and in vivo research models required for the development of drugs and/or vaccines against COVID-19 mediated neurological complications.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"60 1","pages":"85-98"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89170416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Essential Trace Metals as Countermeasure for Lead Toxicity.","authors":"S. Bhattacharya","doi":"10.1615/jenvironpatholtoxicoloncol.2022040132","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2022040132","url":null,"abstract":"Lead (Pb) is the most common toxic heavy metal that is physiologically non-essential and imposes health complications in animals and humans. Chelation therapy is considered as the definite therapy for acute lead toxicity; clinical uses of chelating agents are not recommended in long-term lead toxicity and in children. Research reveals that essential trace metals can counteract empirical Pb toxicity. This article collates the prototypical evidence of the preventive action of essential trace metals towards Pb toxicity in animals. Zinc, selenium, and their combinations are effective here. The key mechanisms of homeostasis of essential metals and cytoprotection are: modulation of signal transduction pathways of apoptosis, inflammation and immune functions (for selenium), attenuation of oxidative stress by augmenting non-enzymatic and enzymatic antioxidative systems and interference in lead accumulation in the body. By means of these mechanisms, these essential trace metals may counteract long-term lead toxicity for susceptible subjects. These mineral nutritional supplementation can easily be employed with no or less adverse effects compared to the typical chelation treatment.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"29 1","pages":"61-67"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78857662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sinem Coskun, M. Gamsızkan, U. Yalçınkaya, M. Sungur
{"title":"STAT3, VEGF, and PSMA Expression Patterns in Malignant Peripheral Nerve Sheath Tumors, Malignant Melanomas, and Glioblastomas: Does Staining Percentage and Intensity Have an Effect on Survival?","authors":"Sinem Coskun, M. Gamsızkan, U. Yalçınkaya, M. Sungur","doi":"10.1615/jenvironpatholtoxicoloncol.2021039719","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039719","url":null,"abstract":"Malignant peripheral nerve sheath tumors (MPNSTs), glioblastomas (GBMs), and malignant melanomas (MMs) are neural crest-originating aggressive tumors with a poor prognosis. Signal transducer and transcription activator 3 (STAT3) plays a role in many biological processes, including cell life and proliferation, the acute phase response, chronic inflammation, autoimmunity, metabolism, and cancer progression, It is also known to be a prooncogenic transcription factor. Vascular endothelial growth factor (VEGF) is one of the most potent proangiogenic stimuli ever identified. It mediates tumor neovascularization, and is associated with angiogenesis and lymphangiogenesis. The prostate-specific membrane antigen (PSMA) folate hydrolase I, despite its name, has been found in tissues other than the prostate. It is overexpressed in prostate cancer cells and several other cancers, and has the potential to be a target for radioligand therapy. We investigated the value of STAT3, VEGF and PSMA immunohistochemical expression patterns and their effects on survival in MPNSTs, GBMs, and MMs. Their expression patterns were evaluated in 25 MPNSTs, 27 GBMs, and 25 MM cases. All GBM cases stained positively for STAT3 and VEGF. In the other groups, the staining patterns were heterogeneous. None of the cases showed positive staining with PSMA. There was no statistically significant difference in survival between cases with differing VEGF and STAT3 staining patterns in the MPSNT and MM groups, but there was an increase in mortality as the VEGF score increased in the GBM group. The suppression of VEGF and STAT3 may be a promising avenue for treatment of MPNSTs, GBMs, and MMs, although further research is needed.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"1 1","pages":"45-53"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89673827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinjun Yang, G. Guo, Minyan Dang, Lei Yan, Xin Kang, Kunjin Jia, Hongrui Ren
{"title":"Assessment of the Therapeutic Effects of Fucoxanthin by Attenuating Inflammation in Ovalbumin-Induced Asthma in an Experimental Animal Model.","authors":"Xinjun Yang, G. Guo, Minyan Dang, Lei Yan, Xin Kang, Kunjin Jia, Hongrui Ren","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019030154","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019030154","url":null,"abstract":"Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"16 1","pages":"229-238"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82396313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Curcumin Modulates Hepatocellular Carcinoma by Reducing UNC119 Expression.","authors":"Zhenjiang Zhao, A. Malhotra, Wu Yuan Seng","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029549","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029549","url":null,"abstract":"UNCI 19 expression has been reported to be significantly higher in hepatic cancer cells (HCC). However, the clinical significance of modulating UNC119 expression in HCC is not well understood. The study described here aimed to explore the potential of curcumin in modulation of UNC119 expression in HCC by assessment with quantitative real-time PCR, western blot, and immune-histochemical analyses in HCC cell lines and tissues. The biological functions of UNC119 in the proliferation, growth, and cycle of tumor cells were analyzed both in vitro and in vivo. UNC119 expression was upregulated in HCC cell lines and tissues as indicated by comparison with normal liver cells and tissues. Cellular function assays showed that higher levels of UNC119 not only promoted proliferation but also enhanced HCC cell migration and invasion. UNC119 promoted progression of the cell cycle and significantly promoted HCC cell growth through the Wnt/β-catenin signal pathway, and enhanced tumor migration and invasion by the TGF-β/EMT pathway. Curcumin efficiently inhibited HCC cell proliferation by blocking the Wnt/β-catenin pathway and inhabited migration and invasion by blocking the TGF-p/EMT signal pathway. Curcumin not only was beneficial for tumor remission but also contributed to the long-term survival of HCC-bearing mice. UNC119 was significantly upregulated and promoted cell growth in hepatic cancer cells and tissues by the Wnt/β-catenin signal pathway and migration by TGF-β/EMT signal pathway. Curcumin treatment inhibited cell proliferation, growth, migration, and invasion by inhibition of those pathways.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"2 1","pages":"195-203"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88760049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Soon, Phui Qi Ng, Jestin Chellian, Thiagarajan Madheswaran, Jithendra Panneerselvam, G. Gupta, S. Nammi, Nicole G. Hansbro, A. Hsu, H. Dureja, M. Mehta, S. Satija, P. Hansbro, K. Dua, T. Collet, D. Chellappan
{"title":"Therapeutic potential of Artemisia vulgaris: An insight into underlying immunological mechanisms.","authors":"L. Soon, Phui Qi Ng, Jestin Chellian, Thiagarajan Madheswaran, Jithendra Panneerselvam, G. Gupta, S. Nammi, Nicole G. Hansbro, A. Hsu, H. Dureja, M. Mehta, S. Satija, P. Hansbro, K. Dua, T. Collet, D. Chellappan","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029397","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029397","url":null,"abstract":"Artemisia vulgaris is a traditional Chinese herb believed to have a wide range of healing properties; it is traditionally used to treat numerous health ailments. The plant is commonly called mugwort or riverside wormwood. The plant is edible, and in addition to its medicinal properties, it is also used as a culinary herb in Asian cooking in the form of a vegetable or in soup. The plant has garnered the attention of researchers in the past few decades, and several research studies have investigated its biological effects, including antioxidant, anti-inflammatory, anticancer, hypolipidemic, and antimicrobial properties. In this review, various studies on these biological effects are discussed along with the tests conducted, compounds involved, and proposed mechanisms of action. This review will be of interest to the researchers working in the field of herbal medicine, pharmacology, medical sciences, and immunology.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"28 1","pages":"205-216"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76741041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Ma, Shi-jun Feng, Dongfang Ai, Yuan Liu, Xiufang Yang
{"title":"D-Pinitol Ameliorates Imiquimod-Induced PsoriasisLike Skin Inflammation in a Mouse Model via the NF-κB Pathway.","authors":"Jing Ma, Shi-jun Feng, Dongfang Ai, Yuan Liu, Xiufang Yang","doi":"10.1615/jenvironpatholtoxicoloncol.2019030782","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2019030782","url":null,"abstract":"Psoriasis is an autoregulated immune and inflammation-based skin disease affecting approximately 3-4% of the worldwide population. Pinitol, conservatively used in ayurvedic medicine, has been shown to disclose an antiinflammatory effect, hold back the T-helper cells, and postpone cardiovascular diseases. In the present study we aimed to reveal the effect of D-pinitol on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model via the nuclear factor-κB (NF-κB) pathway genes. In the current study, we found that D-pinitol ameliorated the skin abrasion and abridged epithelial thickness, inflammation numbers, and collagen-occupied regions in IMQ-induced psoriasis-like mice. The same results (epithelial thickness, inflammation numbers, and collagen-occupied regions) we achieved in dorsal skin regions. In addition, D-pinitol modified the lipid profile and antioxidant enzyme levels, which means that the IMQ-induced group showed elevated malondialdehyde when compared to D-pinitol. Downregulated expression of glutathione, superoxide dismutase, and catalase in the IMQ-induced group was incomparable with D-pinitol, control, and standard group. Additionally, inflammatory and NF-kB pathway gene levels in the psoriatic mouse skin, which includes tumor necrosis factor-α, interleukin [IL]-6, IL-17A, IL-23,TRAF3, NIK, IKKα, and RelB, were dramatically increased or decreased by treatment with D-pinitol. Histological and morphometric studies disclose the efficiency of D-pinitol. Finally, we found that D-pinitol reserved the TRAF3, NIK, IKKα, and RelB in the psoriatic skin, signifying that it restrains the commencement of NF-κB signaling pathways. The present results suggest that D-pinitol could prove to have tremendous preventive potential against the treatment and prevention of inflammatory disease.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"4 1","pages":"285-295"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91248101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yongjian Ji, Hao Sun, Haiqing Liang, Yong Wang, Meili Lu, Zhaoyang Guo, Zhuozhen Lv, W. Ren
{"title":"Evaluation of LncRNA ANRIL Potential in Hepatic Cancer Progression.","authors":"Yongjian Ji, Hao Sun, Haiqing Liang, Yong Wang, Meili Lu, Zhaoyang Guo, Zhuozhen Lv, W. Ren","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019028282","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019028282","url":null,"abstract":"BACKGROUND/AIMS LncRNAs are significant regulators in multiple cancers including hepatocellular carcinoma (HCC). Recently, lncRNA ANRIL has been reported to be elevated during multiple cancer types, exhibiting oncogenic roles. However, the exact biological mechanism of ANRIL is still poorly understood in HCC. METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) assays were utilized to detect expressions of ANRIL, miR-384, and STAT3. CCK8 and EDU assays were employed to evaluate HCC cell proliferation. A flow cytometry assay was used to detect the HCC cell cycle and cell apoptosis. The scratch migration and Transwell invasion assays were performed to test cell migration and invasion, respectively. RIP and RNA pull-down assays were carried out to confirm the correlation between ANRIL and miR-384. The dual-luciferase reporter assay was used to prove the association between miR-384 and STAT3. Western blotting analysis was performed to examine protein levels of STAT3. IHC and HE staining were employed to detect Ki-67 and histopathology. RESULTS ANRIL expression was upregulated in HCC cells, including SMCC7721, HepG2, MHCC-97H, SNU449 and HUH-7 cells, in comparison to the normal human liver cells LO2. Knockdown of ANRIL suppressed HCC cell proliferation and induced cell cycle arrest and apoptosis. HCC cell migration and invasion capacity were inhibited by inhibition of ANRIL. Bioinformatics analyses revealed that ANRIL could interact with miR-384. miR-384 was significantly decreased in HCC cells, and overexpression of miR-384 repressed HCC progression. STAT3 was predicted as a target of miR-384, and miR-384 can modulate STAT3 levels negatively in vitro. ANRIL can suppress HCC development through regulating miR-384 and STAT3 in vivo. CONCLUSION ANRIL is involved in HCC progression by direct targeting of miR-384 and STAT3. Also, ANRIL could act as a potential candidate for HCC diagnosis, prognosis, and therapy.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"29 1","pages":"119-131"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83503834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miao Chen, V. P. Samuel, Yi Wu, Minyan Dang, Yukiat Lin, R. Sriramaneni, S. Sah, Gopala Krishna Chinnaboina, Guang-lin Zhang
{"title":"Nrf2/HO-1 Mediated Protective Activity of Genistein Against Doxorubicin-Induced Cardiac Toxicity.","authors":"Miao Chen, V. P. Samuel, Yi Wu, Minyan Dang, Yukiat Lin, R. Sriramaneni, S. Sah, Gopala Krishna Chinnaboina, Guang-lin Zhang","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029341","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029341","url":null,"abstract":"The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"24 1","pages":"143-152"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87206498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}