scholarly journals Modulation of Tinospora rumphii and Zinc Salt on DNA Damage in Quinoline-Induced Genotoxicity and Hepatotoxicity in Male Albino Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Roger Salvacion Tan ◽  
Lydia M. Bajo
Keyword(s):  
Dna Damage ◽  
Zinc Sulphate ◽  
Chemotherapeutic Agents ◽  
Genotoxic Effect ◽  
Zinc Salt ◽  
Bilirubin Concentration ◽  
Hepatotoxic Effect ◽  
Albino Mice ◽  
Hepatic Injuries ◽  
Dose Dependent

Tinospora rumphii (T. rumphii) is a folkloric medicinal plant that is widely distributed in Asia and Africa. It has been widely used by locals to treat many diseases including jaundice, which is a manifestation of liver damage. We investigated the action of T. rumphii crude extract together with zinc sulphate, a known tumor modulator, on hepatic injuries induced by intraperitoneal (i.p) injections of quinoline on albino mice. The hepatotoxic effect was assessed by bilirubin concentration in the blood serum, while the genotoxic effect was determined by single-cell gel electrophoresis (SCGE). The mice orally fed with the crude extracts, following quinoline exposure, had reduced serum bilirubin concentration and DNA damage. Mice treated with Zinc sulphate, on the other hand, had remarkably reduced DNA damage on hepatocytes. Our findings showed that hepatoprotective potential of T. rumphii extract is dose-dependent and that utilization of the extract as medicinal remedy must be strictly monitored, while zinc was proven to reverse genotoxic effect of quinoline. This study unraveled the potential of T. rumphii extract and zinc as important hepatoprotective agents for future treatment of hepatic damage caused by chemotherapeutic agents used in cancer treatment.

scholarly journals Capability of Hepatic Regeneration of Albino Mice against Hepatic Injuries Induced by Phentolep Drug

2021 ◽  
pp. 228-233
Author(s):  
Sameena Gul Memon ◽  
Pashmina Shaikh ◽  
Fahmida Gul ◽  
Tahseen Ahmed
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Hepatic Regeneration ◽  
Major Theme ◽  
Dosing Regimen ◽  
Regenerative Capacity ◽  
Positive Group ◽  
Liver Injuries ◽  
Albino Mice ◽  
Hepatic Injuries

The major theme of our research was to evaluate the condition of the regenerative capacity of liver with proper consumption of phenytoin medicines with proper precautionary factors. DNA damage was measured through the comet assay via hepatocytes and histological examination was conducted in order to ensure the liver injuries. Current study comprises of four different group of Balb/c albino mice, from them 1st group was facilitated with normal saline as per recommended dose of 1ml/kg. In 2nd group of mice, phenotolep drug was injected with the dose of 12mg/kg for two continuous weeks. Whereas; in 3rd group same, the drug is administered into the mice with same dosing regimen for 02 weeks and then allowed to recover for 02 weeks. In the last group of mice, phenotolep was given to the remaining mice with a similar regimen and managed for 04 weeks for normal physiological functions and it was concluded that induction of phentolep among various groups of mice can induce alteration the nucleus of hepatocytes and ultimately variation occurred within DNA. 3rd and 4th groups showed quite differ results than the positive group as regression was observed in these groups and restore the normal physiology of the liver and the current study indicates that hepatic injuries can be sorted out with passage of time.

scholarly journals Anthracycline-induced cytotoxicity in the GL261 glioma model system

2021 ◽  
Author(s):  
Amber M. Tavener ◽  
Megan C. Phelps ◽  
Richard L. Daniels
Keyword(s):  
Cell Viability ◽  
Tumor Cells ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Effects ◽  
High Concentrations ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Gl261 Glioma

AbstractGlioblastoma (GBM) is a lethal astrocyte-derived tumor that is currently treated with a multi-modal approach of surgical resection, radiotherapy, and temozolomide-based chemotherapy. Alternatives to current therapies are urgently needed as its prognosis remains poor. Anthracyclines are a class of compounds that show great potential as GBM chemotherapeutic agents and are widely used to treat solid tumors outside the central nervous system. Here we investigate the cytotoxic effects of doxorubicin and other anthracyclines on GL261 glioma tumor cells in anticipation of novel anthracycline-based CNS therapies. Three methods were used to quantify dose-dependent effects of anthracyclines on adherent GL261 tumor cells, a murine cell-based model of GBM. MTT assays quantified anthracycline effects on cell viability, comet assays examined doxorubicin genotoxicity, and flow cytometry with Annexin V/PI staining characterized doxorubicin-induced apoptosis and necrosis. Dose-dependent reductions in GL261 cell viability were found in cells treated with doxorubicin (EC50 = 4.9 μM), epirubicin (EC50 = 5.9 μM), and idarubicin (EC50 = 4.4 μM). Comet assays showed DNA damage following doxorubicin treatments, peaking at concentrations of 1.0 μM and declining after 25 μM. Lastly, flow cytometric analysis of doxorubicin-treated cells showed dose-dependent induction of apoptosis (EC50 = 5.2 μM). Together, these results characterized the cytotoxic effects of anthracyclines on GL261 glioma cells. We found dose-dependent apoptotic induction; however at high concentrations we find that cell death is likely necrotic. Our results support the continued exploration of anthracyclines as compounds with significant potential for improved GBM treatments.

scholarly journals Evaluation of Dimer of Epicatechin from an Endophytic Fungus Curvularia australiensis FC2AP on Acute Toxicity Levels, Anti-Inflammatory and Anti-Cervical Cancer Activity in Animal Models

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 654
Author(s):  
Vellingiri Manon Mani ◽  
Arockiam Jeyasundar Parimala Gnana Soundari ◽  
Balamuralikrishnan Balasubramanian ◽  
Sungkwon Park ◽  
Utthapon Issara ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Acute Toxicity ◽  
Endophytic Fungus ◽  
Lethal Dose ◽  
Chemotherapeutic Agents ◽  
Cancer Drug ◽  
Dependent Manner ◽  
Anti Cancer ◽  
Albino Mice ◽  
Anti Inflammatory

Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells or altering the properties of the cells. In order to reduce the severity of the side effects caused by the chemically synthesized therapeutic agents, the current research developed an anti-cancer agent dimer of epicatechin (DoE), a natural bioactive secondary metabolite (BSM) mediated from an endophytic fungus Curvularia australiensis FC2AP. The investigation has initiated with the evaluation of inhibiting the angiogenesis which is a main activity in metastasis, and it was assessed through Hen’s Egg Test on Chorio Allantoic Membrane (HET-CAM) test; the BSM inhibited the growth of blood vessels in the developing chick embryo. Further the DoE was evaluated for its acute toxicity levels in albino mice, whereas the survival dose was found to be 1250 mg/kg and the lethal dose was 1500 mg/kg body weight of albino mice; hematological, biochemical, and histopathological analyses were assessed. The anti-inflammatory responses of the DoE were evaluated in carrageenan induced Wistar rats and the reduction of inflammation occurred in a dose-dependent manner. By fixing the effective dose for anti-inflammation analysis, the DoE was taken for the anti-cervical cancer analysis in benzo (a) pyrene induced female Sprague-Dawley rats for 60 days trial. After the stipulated days, the rats were taken for hematological antioxidants, lipid peroxidation (LPO), member bound enzymes, cervical histopathological and carcinogenic markers analyses. The results specified that the DoE has the capability of reducing the tumor in an efficient way. This is the first report of flavonoid-DoE production from an endophytic fungus C. australiensis has the anticancer potentiality and it can be stated as anti-cancer drug.

scholarly journals Regulation of p73-mediated apoptosis by c-Jun N-terminal kinase

2007 ◽  
Vol 405 (3) ◽  
pp. 617-623 ◽  
Author(s):  
Emma V. Jones ◽  
Mark J. Dickman ◽  
Alan J. Whitmarsh
Keyword(s):  
Dna Damage ◽  
Stress Responses ◽  
Tumour Progression ◽  
Chemotherapeutic Agents ◽  
Signalling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
P53 Family ◽  
Jnk Pathway ◽  
Mitogen Activated Protein ◽  
Induced Apoptosis

The JNK (c-Jun N-terminal kinase)/mitogen-activated protein kinase signalling pathway is a major mediator of stress responses in cells, including the response to DNA damage. DNA damage also causes the stabilization and activation of p73, a member of the p53 family of transcription factors. p73, like p53, can mediate apoptosis by up-regulating the expression of pro-apoptotic genes, including Bax (Bcl2-associated X protein) and PUMA (p53 up-regulated modulator of apoptosis). Changes in p73 expression have been linked to tumour progression, particularly in neuroblastomas, whereas in tumours that feature inactivated p53 there is evidence that p73 may mediate the apoptotic response to chemotherapeutic agents. In the present study, we demonstrate a novel link between the JNK signalling pathway and p73. We use pharmacological and genetic approaches to show that JNK is required for p73-mediated apoptosis induced by the DNA damaging agent cisplatin. JNK forms a complex with p73 and phosphorylates it at several serine and threonine residues. The mutation of JNK phosphorylation sites in p73 abrogates cisplatin-induced stabilization of p73 protein, leading to a reduction in p73 transcriptional activity and reduced p73-mediated apoptosis. Our results demonstrate that the JNK pathway is an important regulator of DNA damage-induced apoptosis mediated by p73.

Comparative evaluation of genotoxic effect in subjects with chronic periodontitis with and without type 2 diabetes mellitus

2019 ◽  
Vol 11 (1) ◽  
pp. 29-36
Author(s):  
Dr.Smruti Lulla ◽  
Dr.Amita Mali ◽  
Dr. AashwiinMiglani ◽  
Dr. VidyaDodwad ◽  
Dr. SachinMangalekar ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Dna Damage ◽  
Type 2 Diabetes Mellitus ◽  
Chronic Periodontitis ◽  
Periodontal Diseases ◽  
Genotoxic Effect ◽  
Micronucleus Frequency ◽  
Group A

Aims: The aim of the study was to compare the genotoxic effect by assessing the micronucleus frequency (MNF), as a biomarker for DNA damage, in subjects with chronic periodontitis with and without type 2 Diabetes Mellitus. Methods and Material: For the study, a total of 65 subjects were take and divided into three groups. Group A included 30 subjects with Generalised Chronic Periodontitis, Group Bincluded 30 Subjects with Chronic Periodontitis with type 2 diabetes mellitus and Group C included 5 systemically and periodontally healthy subjects. Periodontal clinical examination was carried out. A slide was prepared using the blood sample collected from the subjects which was fixed in 5% geimsa solution and was observed under the microscope. Later the scoring of micronuclei was done. Statistical analysis used: Descriptive and inferential statistical analyses were carried out in the present study. Analysis of Variance (ANOVA) was used to find the significance of study parameters and test the equality of three or more means of more than two groups. Tukey’s post hoc analysis was used to compare parameters of each and every group. Results: The mean score of the micronuclei observed in group A, B and C were 10.23, 14.87 and 1 respectively i.e. group B showed significantly greater damage than other two groups. Conclusions: It was concluded that the score of micronucleus frequency may be considered as an important biomarker of genotoxic damage that is DNA damage in subjects with chronic localised as well as systemic diseases like type 2 diabetes, as well as Periodontal diseases.

Detraction of Diclofenac-Associated Hepatotoxicity by Fresh Beet Root Juice in Male Albino Mice

2021 ◽  
Vol 72 (2) ◽  
pp. 19-26
Author(s):  
Tahani Mohamad Alhazani ◽  
Badr Abdullah Aldahmash ◽  
Doaa Mohamed El-Nagar ◽  
Khalid Elfaki Ibrahim ◽  
Saheed Olaide Anifowose ◽  
...  
Keyword(s):  
Liver Enzymes ◽  
Immunohistochemical Analysis ◽  
Control Group ◽  
Beet Root ◽  
Hepatotoxic Effect ◽  
Anti Oxidant ◽  
Albino Mice ◽  
Anti Inflammatory ◽  
Pre Treatment ◽  
Main Component

The beet root as dietary supplement hepatoprotective ability has gained interest in recent days. The present study was designed to determine the potential hepatoprotective effect of beet root juice as anti-inflammatory and anti-oxidant agent to eliminate the hepatotoxic effect of diclofenac as wide spread analgesic agent. Male albino mice were divided randomly into 4 groups, the 1st group served as control group, the 2nd group received 8 mL/kg of freshly prepared beet root juice, the 3rd group received oral administration 20 mg/kg of diclofenac and the 4th group pre-treated with beet root before one-hour diclofenac administration for 30 days. Biochemical results revealed sharp significant raised levels of liver enzymes level (AST, ALT, ALP and GGT) in the 3rd group that received diclofenac, besides to marked pathological changes manifested by high pathological scoring system such as hepatocytes degeneration, ballooning, infiltration and fibrosis. Immunohistochemical analysis elucidated massive incidence of MDA as an indicator of oxidative stress, moreover great number of neutrophils were seen as main component of inflammation. Whereas, pre-treatment of beet root juice one hour before diclofenac resulted in significant decrease of liver enzymes, clear attenuation of pathological features, decrease of pathological score. A great reduction of MDA in liver tissue and number of neutrophils stained histochemically. It was concluded that beet root juice possessed beneficial hepatoprotective role against diclofenac, as significant anti-oxidant and anti-inflammatory effect.

scholarly journals Ubiquitin and Ubiquitin-Like Proteins Are Essential Regulators of DNA Damage Bypass

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2848
Author(s):  
Nicole A. Wilkinson ◽  
Katherine S. Mnuskin ◽  
Nicholas W. Ashton ◽  
Roger Woodgate
Keyword(s):  
Dna Damage ◽  
Cancer Progression ◽  
Chemotherapeutic Agents ◽  
Tumor Formation ◽  
Human Cells ◽  
Double Strand Breaks ◽  
Template Switching ◽  
Post Translational Modifications ◽  
Strand Breaks ◽  
Exogenous Factors

Many endogenous and exogenous factors can induce genomic instability in human cells, in the form of DNA damage and mutations, that predispose them to cancer development. Normal cells rely on DNA damage bypass pathways such as translesion synthesis (TLS) and template switching (TS) to replicate past lesions that might otherwise result in prolonged replication stress and lethal double-strand breaks (DSBs). However, due to the lower fidelity of the specialized polymerases involved in TLS, the activation and suppression of these pathways must be tightly regulated by post-translational modifications such as ubiquitination in order to limit the risk of mutagenesis. Many cancer cells rely on the deregulation of DNA damage bypass to promote carcinogenesis and tumor formation, often giving them heightened resistance to DNA damage from chemotherapeutic agents. In this review, we discuss the key functions of ubiquitin and ubiquitin-like proteins in regulating DNA damage bypass in human cells, and highlight ways in which these processes are both deregulated in cancer progression and might be targeted in cancer therapy.

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