Co-occurrence of Wilson disease and Auto-Immune Hepatitis in 14-year-old female: A case report

Unusual cases of coexistence between Wilson's disease and autoimmune hepatitis have occurred. There are characteristics of both diseases in this community of patients, and laboratory and histo pathological findings can be misleading. Wilson disease's clinical appearance can differ widely; thus, there is not always an easy diagnosis. In addition to being childhood and young adult illnesses, Wilson's disease can also be triggered at any age. Liver disease and cirrhosis, neuropsychiatric disorders, Kayser-Fleischer(KF.) rings, and acute hemolysis events are the primary characteristics of Wilson's disease, frequently in combination with acute liver failure. Diagnosis is extremely difficult for children and adults with active liver disease. None of the latest Wilson's disease laboratory tests are optimal and may not be specific. Therefore, by taking into account acute hepatitis similar to Wilson's disease and autoimmune hepatitis, concomitant treatment with immunosuppression and penicillamine may have a superior impact

Evaluation of anti-proliferative activity of simvastatin and atorvastatin on MCF7 cell line compared with doxorubicin using MTT test

Statins are effective to lower the cholesterol level and protect against cardiovascular disease. Recent studies showed that statins have pleiotropic effect and can be used to treat many types of diseases like neurodegenerative disorders, stroke, and cancer. Statins inhibit cell proliferation by suppression of mevalonate pathway leading to desregu-lation of cell signal transduction of some membrane receptor protein which is important for gene transcription. This study was done to evaluate the anti-proliferative activity of simvastatin and atorvastatin on MCF7 cell line alone and in combination with anathracycline chemotherapy drug (doxo-rubicin) using MTT assay. The results showed that simvastatin and atorvastatin had significant anti-proliferative effect on MCF7 cell line in dose-dependent manner with an IC50 10.10 μM and 12.3 μM respect-tively. Moreover, the combination of atorvastatin and simvastatin with (1 μM) doxorubicin had higher cytotoxic effect with an IC50 = 0.07 μM and 0.05μM respectively than doxoru-bicin alone IC50 = 1.9 μM. In conclusion, simvastatin and atorvastatin had anti-proliferative effect on MCF7 cell line and displayed significant synergism with doxorubicin which will help in enhancing efficacy of doxorubicin and decrease the adverse effect

The Potential Effect of Simvastatin on Regulatory T cells in Experimentally Induced Autoimmune Thyroiditis in Female Rats

Autoimmune thyroiditis also named Hashimoto's thyroiditis: is an inflammatory disorder of the thyroid gland. It is characterized by circulating antibodies to thyroid antigens, and enlargement of the gland with lymphocytic infiltration. Regulatory T cells (Tregs), a particular subset of CD4+ T cells that express CD25 at a markedly increased level. they can regulate immune response in order to preserve homeostasis and self-tolerance. T cell expansion and cytokine production are restricted by Tregs. The development of this autoimmune disease is influenced by TGF-ß1 shortage. Management of HT is usually a symptomatic therapy that concentrates on HT's symptoms rather than its underlying cause. Statins, the lipid lowering medications have pleotropic effects. they can alter immunological reactions. Twenty-four female rats were used for this experiment divided into four groups (n=6), the disease was induced in all groups except group1 (control) where rats only received phosphate buffer saline, group 2 (induction group), group 3 received Prednisolone 2mg\kg orally for 30 days and group 4 received Simvastatin (4mg\kg) orally for 30 days too. Hashimoto’s thyroiditis was induced experimentally by subcutaneous injection of porcine thyroglobulin in Freund’s adjuvant emulsion (4mg/ml). Results showed an increase in Tregs and serum TGF-ß level in rats treated with simvastatin. In conclusion, simvastatin improves the number of functioning Tregs and increases TGF-ß signaling to suppress the autoimmune reaction. Therefore, simvastatin can be a promising approach in the treatment of this disease

Nrf2 as a modulator of oxidative stress

Nrf2 is active protein presents in the cytoplasm in the cells of the body. In the presence of an activators, Nrf2 can enter the nucleus which bind to Antioxidant Responses Elements (ARE) or otherwise named human ARE (hARE) which control the whole antioxidants activity in human cell. Many factors may contribute to defective or overwhelmed cellular antioxidants activities for instances aging and cellular damages. These cellular damages can be produced by free radicals or oxidative stress. In the mechanism, if Nrf2 activated in the nucleus, can caused the production of collaborative antioxidants enzymes especially: catalase, glutathione (GLT) and superoxide dismutase (SOD) as a responsible for detoxification of free radical inside the cells

Nuclear Factor Erythroid-2 Linked Factor (Nrf2) as a Potential Mediator of Hepatotoxicity

Hepatotoxicity is a term used to describe serious health complications of liver disease caused by a variety of factors. Nuclear factor erythroid-2 linked factor (Nrf2) as a potential mediator of hepatotoxicity via inflammatory and induction of oxidative stress, oxidation produces more toxic compounds caused more pathogenic cases; therefore, to maintain sufficient homeostasis, involve antioxidant materials and detoxification factors. Controlling cytokine activity in normal cells is a useful way to regulate the signaling pathway of Nrf2. Recent studies found a relation between each Nrf2 and NF-κB activation and drug-induced liver injury.  This review presents a detailed and conformation update of Nrf2 roles in hepatotoxicity which considers that drug-induced liver injury is the main problem to draw attention in medical clinics and to develop new drugs with less harmful to the liver. In addition to that. Kept each of normal oxidation and cytokines levels is crucial responses for cells alteration and remaining to survive

The Protective Effect of Metformin Against Doxorubicin Induced Cardiotoxicity in Rabbits

Back ground: Doxorubicin is a very effective anticancer therapy of the anthracycline's family used in many pediatric and adult cancers. However, due to severe cardiotoxicity adverse effect, the uses of doxorubicin are limited. Metformin reducing basal and postprandial glucose levels. Metformin has a good treatment efficacy and safety profile in treatment of T2DM in conjunction with lifestyle modification. Metformin have a cardioprotective effect in addition to reducing basal and postprandial levels of glucose by decreasing the production of reactive oxygen species, maintaining energy homeostasis and apoptosis regulation by its activation of adenosine monophosphate-activated protein kinase.  Method: Thirty-six white male rabbits randomly divided to six groups, each comprising of six rabbits. 1- Control group injected 2 ml saline single dose intraperitoneally. 2- Metformin group 300 mg/kg/daily for 14 days orally. 3- Acute doxorubicin induction group 16 mg/ kg intraperitoneally as a single dose. 4- Chronic doxorubicin induction group 4mg/kg intraperitoneally twice a week for two weeks. 5- Metformin+ acute doxorubicin induction group 16 mg/kg intraperitoneally single dose and Metformin 300 mg/kg/daily for 14 days orally, three days before doxorubicin treatment. 6- Metformin + chronic doxorubicin induction group 4 mg/kg intraperitoneally, twice a week for two weeks and Metformin 300 mg/kg/daily for 14 days orally, three days before doxorubicin treatment.  Result: our results revealed the treatment with metformin significantly (p < 0.05) reduced the serum level of troponin I and MMP2 in Metformin+ acute doxorubicin induction and Metformin + chronic doxorubicin induction groups in comparison with the acute doxorubicin and chronic doxorubicin groups. Conclusion: From these results in this study, we can conclude that metformin has a cardioprotective effect against doxorubicin induced cardiotoxicity in acute and also the chronic induction by decreasing serum level of troponin I and MMP2

SIRT1 activators as novel therapy for cancer

Sirutins 1-7 (SIRT1-7) is an enzyme that depends on NAD+ to be activated, making it a member of the 3rd class of Deacetylase enzymes. SIRT1-7’s activity is involved with metabolism, cell survival and/or death as well as DNA repair, gene repression, inflammatory responses, the   aging process, neuroprotection in addition to possibly helping with the treatment of cancer. Molecules that could have a modifying effect on SIRT1-7’s activity has caught a great attention recently, owing to the fact of how beneficial this enzyme could be. In this review, we attempt to shed a light on these activator compounds and their use in Sirutin activation therapy, particularly SIRT1, for it is the most researched type. One of these compounds is Resveratrol, a natural compound that –due to its SIRT 1 activation potential – could help in the treatment of obesity, prevention of tumor formation as well as decrease in heart function and neuronal loss related to aging; however, Resveratrol has poor bioavailability, which is why structurally reformulated compounds and molecules have been developed. Other molecules that are different from Resveratrol such as SRT1720, SRT2104 and SRT2379 in addition to others, have been used and shown greater activation potential for SIRT1 than Resveratrol

Lipidomics application to explain acute cardiotoxicity induced by doxorubicin

Doxorubicin (DOX) induced cardio-toxicity is one of the important limiting factors for the clinical use of this drug, the exact mechanism underlying the cardiotoxicity is still under debate and different experimental protocols were used.  Lipidomics technology was used in this study to investigate the underlying the cardiotoxicity is still under debate and different experimental protocols were used.  Lipidomics technology was used in this study to investigate the underlying mechanism of cardiotoxicity induced by DOX.  Lipidomics refers to the complete analysis of lipid profile of a cell or organism based on the principles and tools of analytical chemistry particularly mass spectrometry. This study was designed to investigate cardiotoxicity induced by doxorubicin using lipidomics technology. Method: Twelve adult male rats divided randomly into two groups, each group comprising of six rats. 1: Control group (single dose (1ml) saline intraperitoneally); 2: DOX group (20 mg/ kg single dose intraperitoneally). After anesthesia, the myocardial tissue harvested and stored in liquid nitrogen, then the metabolites will be extracted from left ventricle of the heart tissue, derivatized using boron trifluride-methanol 10% and then the metabolites identified using GC-MS. Results: The results showed that treatment with DOX produced significant (P<0.05) increase in the level of acetic acid, cholesterol, myristic acid, and stearic acid. Whereas the level of arachidonic acid, linolic acid, pentadecanoic acid, oleic acid and ricinoleic acid, decreased significantly (P<0.05) in DOX group.  Lauric acid, palmitic acid, and methylcyclohexane, were found to be increased in DOX group. Conclusion: This study showed that DOX induced cardiotoxicity can be identified by lipidomics technique by measuring lipid biomarkers of cardiotoxicity in heart tissue which include the saturated fatty acids (stearic acid, acetic acid and palmitic acid), unsaturated fatty acids (arachidonic acid, linoleic acid, and oleic acid) as well as cholestero

In Vivo Study of the Anticancer Activity of Doxorubicin Loaded on a Cellulose-Based Nanocarrier System

Many cancer treatment protocols regard doxorubicin as a one of the most effective anticancer agents available to treat different types of cancer. Its mechanisms of action include either intercalation with the DNA of the cancerous cells, production of reactive oxygen species ROS or it acts by inhibition of topoisomerase TOP IIα. The international administration of doxorubicin is associated with a real problem which is cancer cells resistance, which is a worldwide problem that reduced its usage. Therefore, in this study doxorubicin was loaded on a cellulose-based nanocarrier system [Cellulose Nanowhiskers (CNWs)] as an attempt to increase its intracellular concentration and reduce its resistance. The effect of the loaded doxorubicin was evaluated by measuring the reduction in the size of the tumor masses those induced by intra peritoneal administration of adenocarcinoma cells (AM3) to a group of albino mice. This study was performed in comparison with unloaded doxorubicin and it was found that the loaded doxorubicin produced a significant reduction in tumor size with suspended antitumor effect compared to the unloaded doxorubicin

Role of miRNA in drug-induced hepatic injury

Acute liver disease is characterized by loss of liver function within days or weeks however, in the patient who is not previously diagnosed, its less common compared with chronic liver failure, which developed slowly and irreversible process. It’s caused by   drug-induced liver damage (DILI) therefore identifying liver injury is challenging for clinical treatment and diagnosis. The major causes of liver failure involve toxic metabolites of some medications that consumed Adenosine Tri Phosphate (ATP) compared with normal conditions and increased oxidative stress due to overexpression of MicroRNAs, it is necessary to do complete diagnosis of patients. Biomarker parameters can be utilized to validate liver damage like microRNAs (miRNAs) analysis, it is a more receptive marker because increased earlier than the transaminases enzymes allowing for a more accurate diagnosis.  we summarized recent signs of progress disease concerning the role of miRNA as a novel DILI biomarker, the miRNA levels can be measured in plasma, saliva, urine, fetal fluid (amniotic), as well as other materials either in human or animals like mice, rats which significantly elevate during illness, therefore, provide e specific biomarker of hepatoinjury