Search results for: liver foci

Authors: V. R. Ahire, A. Kumar, B. N. Pandey, K. P. Mishra, G. R. Kulkarni

Abstract:

Radiation therapy is an effective vital strategy used globally in the treatment of cervical cancer. However, radiation efficacy principally depends on the radiosensitivity of the tumor, and not all patient exhibit significant response to irradiation. A radiosensitive tumor is easier to cure than a radioresistant tumor which later advances to local recurrence and metastasis. Herbal polyphenols are gaining attention for exhibiting radiosensitization through various signaling. Current work focuses to study the radiosensitization effect of ellagic acid (EA), on HeLa cells. EA intermediated radiosensitization of HeLa cells was due to the induction γ-H2AX foci formation, G1 phase cell cycle arrest, and loss of reproductive potential, growth inhibition, drop in the mitochondrial membrane potential and protein expression studies that eventually induced apoptosis. Irradiation of HeLa in presence of EA (10 μM) to doses of 2 and 4 Gy γ-radiation produced marked tumor cytotoxicity. EA also demonstrated radio-protective effect on normal cell, NIH3T3 and aided recovery from the radiation damage. Our results advocate EA to be an effective adjuvant for improving cancer radiotherapy as it displays striking tumor cytotoxicity and reduced normal cell damage instigated by irradiation.

Keywords: apoptotic radiosensitivity, ellagic acid, mitochondrial potential, cell-cycle arrest

Procedia PDF Downloads 353

Authors: Bing-Fang Lee, Srinivasan Periasamy, Ming-Yie Liu

Abstract:

Shift work sleep disorder is a common problem in industrialized world. It is a type of circadian rhythmic sleep disorders characterized by insomnia and sleep deprivation. Lack of sleep in workers may lead to poor health conditions such as hepatic dysfunction. Melatonin is a hormone secreted by the pineal gland to alleviate insomnia. Moreover, it is a powerful antioxidant and may prevent acute liver injury. Therefore, workers take in melatonin to deal with sleep-related health is an important issue. The aim of this study was to investigate the effect of melatonin on an acute hepatic injury model sinusoidal obstruction syndrome (SOS) in mice. Male C57BL/6 mice were injected with a single dose (500 mg/kg) of monocrotaline (MCT) to induce SOS. Melatonin (1, 3, 10 and 30 mg/kg) was injected 1 h before MCT treatment. After 24 h of MCT treatment, mice were sacrificed. The blood and liver were collected. Organ damage was evaluated by serum biochemistry, hematology analyzer, and histological examination. Low doses of melatonin (1 and 3 mg/kg) had no protective effect on SOS. However, high doses (10 and 30 mg/kg) exacerbated SOS. In addition, it not only increased serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and extended liver damage indicated by histological examination but also decreased platelet levels, lymphocyte ratio, and glutathione level; it had no effect on malondialdehyde and nitric oxide level in SOS mice. To conclude, melatonin may exacerbate MCT-induced SOS in mice. Furthermore, melatonin might have a synergistic action with SOS. Usage of melatonin for insomnia by people working in long shift must be cautioned; it might cause acute hepatic injury.

Keywords: acute liver injury, melatonin, shift work, sleep deprivation

Procedia PDF Downloads 191

Authors: Anit S. Malhotra, Ajay Duseja, Neelam Chadha

Abstract:

Endothelial dysfunction is a precursor to atherosclerosis, and flow-mediated dilatation (FMD) in the brachial artery is the commonest method to evaluate endothelial function in humans. Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders encountered in clinical practice. An earlier meta-analysis had quantitatively assessed the degree of endothelial dysfunction using FMD. However, the largest study investigating the relation of FMD with NAFLD was published after that meta-analysis. In addition, that meta-analysis did not include some studies, including one from our centre. Therefore, an updating the previous meta-analysis was considered important. We searched PubMed, Cochrane Library, Embase, Scopus, SCI, Google Scholar, conference proceedings, and references of included studies till June 2017 to identify observational studies evaluating endothelial function using FMD in patients with non-alcoholic fatty liver disease. Data was analyzed using MedCalc. Fourteen studies were found eligible for inclusion in the meta-analysis. Patients with NAFLD had lower brachial artery FMD as compared to controls, standardized mean difference (random effects model) being –1.279%; 95% confidence interval (CI), –1.478 to –0.914. The effect size became smaller after addition of the recent study with the largest sample size was included compared with the earlier meta-analysis. In conclusion, patients with NAFLD had low FMD values indicating that they are at a higher risk of cardiovascular disease although our results suggest the effect size is not as large as reported previously.

Keywords: endothelial dysfunction, flow-mediated dilatation, meta-analysis, non-alcoholic fatty liver disease

Procedia PDF Downloads 190

Authors: Nora Mohammed Al-Kehayez

Abstract:

This present investigation was performed to study the effect of low fat yogurt on serum and liver lipids profile of male albino rats (weighing 100 g+or- 5 gram) when fed balanced or high fat high cholesterol diets and given yogurt ad libitum compared with control groups. Rats were divided into 4 groups, each group contains 6 rats. The groups of rats were fed as follows: Group(1) was fed balanced diet + water(control). Group(2) was fed balanced diet + low fat yogurt. Group(3) was fed high fat high cholesterol diet + water(Control). Group(4) was fed high fat high cholesterol diet + low fat yogurt. The obtained results could be summarized as follows: When rats were given low fat yogurt and fed balanced or high fat high cholesterol diets a significantly greater weight gains resulted in comparison with the control groups given water instead of yogurt. The data on the weights of liver and heart expressed' as percentage increased the body weight in case of rats which were fed balanced diet with low fat yogurt while in case of rats which were fed high fat high cholesterol diet with low fat yogurt the increment scenes to be less. Results of serum cholesterol levels in serum of rats were given balanced or high fat high cholesterol diets and consuming low fat yogurt was showed a significant reduction values. However the low fat yogurt produced the highest significant decrease values. The values of serum cholesterol go hand in hand with serum lipoprotein fractions in rats given low fat yogurt with both balanced or high fat high cholesterol diets. An increase of high density lipoprotein HDL-C and a decrease of low density lipoprotein LDL-C values were obtained. When rats ingested low fat yogurt a significant decrease in serum and liver triglycerides content was obtained wether with balanced or high fat high cholesterol diets. Rats consuming high fat high cholesterol diets with water showed a significant increase in liver total lipids, total cholesterol and phospholipides levels in comparison with the same liver parameters in rats given balanced diet with water. Supplement with low fat yogurt significantly suppressed these effects.

Keywords: yogurt, lipids profile, albino, rats

Procedia PDF Downloads 421

Authors: Imeobong Joseph Inyang, Aniekan-Augusta Okon Eyo, Abel William Essien

Abstract:

Hepatitis B virus (HBV) is one of the known human carcinogens. The presence of HBsAg in liver tissues indicates active viral replication. More than 85% of Hepatocellular Carcinoma (HCC) cases occur in countries with increased rates of chronic HBV infection. An evaluation study to determine the relationship between positivity for HBsAg and development of HCC and its distribution between age and gender of subjects was done. Shikata Orcein and Haematoxylin and Eosin (H&E) staining techniques were performed on liver sections. A total of 50 liver tissue specimens comprising 38 biopsy and 12 post-mortem specimens were processed. Thirty-five of the 50 specimens were positive for HBsAg with Orcein stain whereas only 16 were positive with H&E stain, and these were also positive with Orcein stain, giving an HBsAg prevalence of 70.0% (35/50). The prevalence of HCC in the study was 56.0% (28/50), of which 21 (75.0%) cases were positive for HBsAg, 18 (64.3%) were males while 10 (35.7%) were females distributed within the age range of 20-70 years. The highest number of HBsAg positive HCC cases, 7/21 (33.3%) occurred in the age group 40-49 years. There was no relationship in the pattern of distribution of HCC between age and gender using the Pearson correlation coefficient (r = 0.0474; P < 0.05). HBV infection predisposed to HCC. Orcein technique was more specific and is therefore recommended for screening of liver tissues where facilities for immunohistochemistry are inaccessible.

Keywords: Hepatitis B. surface antigen, hepatocellular carcinoma, orcein, pathology

Procedia PDF Downloads 312

Authors: Manisha, Manisha Mathur, Jay K. Desai, Shesh Asopa, Manisha Mehra

Abstract:

The present study was carried out for the comprehensive analysis of lumpy skin disease (LSD) in cattle and to elucidate the histopathology of vital organs in natural outbreaks. Lumpy skin disease (LSD) is a viral infection that primarily affects cattle. It is caused by a Capri pox virus and is characterized by the formation of skin nodules or lesions. For this study, a postmortem of 20 cows who died of Lumpy skin disease in different regions of Rajasthan was conducted. This study aimed to examine a cow's external and internal organs to confirm if lumpy skin disease was the cause of death. Accurate diagnosis is essential for improving disease surveillance, understanding the disease's progression, and informing control measures. Pathological examinations reveal virus-induced changes across organs, while histopathological analyses provide crucial insights into the disease's pathogenesis, aiding in the development of advanced diagnostics and effective prevention strategies. Histopathological examination of nodular skin lesions revealed edema, hyperemia, acanthosis, severe hydropic degeneration/ballooning degeneration, and hyperkeratosis in the epidermis. In the lungs, congestion, oedema, emphysema, and atelectasis were observed grossly. Microscopically changes were suggestive of interstitial pneumonia, suppurative pneumonia, bronchopneumonia post pneumonic fibrosis, and stage of resolution. Grossely liver showed congestion and necrotic foci microscopically in most of the cases, and the liver showed acute viral hepatitis. Microscopically in kidneys, multifocal interstitial nephritis was observed. There was marked interstitial inflammation and zonal fibrosis with cystically dilated tubules and bowman's capsules. Microscopically, most of the heart tissue section showed normal histology with few sarcocysts in between cardiac muscles. In some cases, loss of cross striation, sarcoplasmic vacuolation, fregmentation, and disintegration of cardiac fibres were observed. The present study revealed the characteristic gross and histopathological changes in different organs in natural cases of lumpy skin disease. Further, the disease was confirmed based on the molecular diagnosis and transmission electron microscopy of capripox infection in the affected cattle in the study area.

Keywords: Capripoxvirus, lumpy skin disease, polymerage chain reaction, transmission electron microscopy

Procedia PDF Downloads 23

Authors: Deepak Mohan, Sushma Sharma

Abstract:

Diclofenac sodium, a member of the acetic acid family of non-steroidal anti-inflammatory drugs, is used to retard inflammation, arthritis pain and ankylosing spondylitis. The drug is known to cause severe injury in different tissues due to formation of reactive oxygen species. The present study is focused on the effect of different doses of diclofenac (4 mg/kg/body weight and 14 mg/kg/body weight on histoarchitecture of the liver from 7-28 days of the investigation. Diclofenac administration resulted in distorted hepatic degeneration and formation of wide areas in the form of sinusoidal gaps. Hepatic fibrosis noticed in different stages of investigation could be attributed to chronic inflammation and reactive oxygen species which results in deposition of extracellular matrix proteins. The abrupt degenerative changes observed during later stages of the experiment showed maximum damage to the liver, and there was enlargement of sinusoidal gaps accompanied by maximum necrosis in the tissues.

Keywords: arthritis, diclofenac, histoarchitecture, sinusoidal

Procedia PDF Downloads 269

Authors: N. F. Hamid, A. Kipar, J. Stewart, D. J. Antoine, B. K. Park, D. P. Williams

Abstract:

Acetaminophen (APAP) is a widely used analgesic that is safe at therapeutic doses. The mouse model of APAP has been extensively used for studies on pathogenesis and intervention of drug induced liver injury based on the CytP450 mediated formation of N-acetyl-p-benzo-quinoneimine and, more recently, as model for mechanism based biomarkers. Delay of the fasted CD1 mice to rebound to the basal level of hepatic GSH compare to fed mice is reported in this study. Histologically, 15 hours fasted mice prior to APAP treatment leading to overall more intense cell loss with no evidence of apoptosis as compared to non-fasted mice, where the apoptotic cells were clearly seen on cleaved caspase-3 immunostaining. After 15 hours post APAP administration, hepatocytes underwent stage of recovery with evidence of mitotic figures in fed mice and return to completely no histological difference to control at 24 hours. On the contrary, the evidence of ongoing cells damage and inflammatory cells infiltration are still present on fasted mice until the end of the study. To further measure the regenerative capacity of the hepatocytes, the inflammatory mediators of cytokines that involved in the progression or regression of the toxicity like TNF-α and IL-6 in liver and spleen using RT-qPCR were also included. Yet, quantification of proliferating cell nuclear antigen (PCNA) has demonstrated the time for hepatic regenerative in fasted is longer than that to fed mice. Together, these data would probably confirm that fasting prior to APAP treatment does not only modulate liver injury, but could have further effects to delay subsequent regeneration of the hepatocytes.

Keywords: acetaminophen, liver, proliferating cell nuclear antigen, regeneration, apoptosis

Procedia PDF Downloads 430

Authors: Toumi Farah, Charallah Salima

Abstract:

In the Algerian Sahara, goat farming is predominant, and it’s associated with other types of breeding, particularly camel and sheep; it also constitutes a significant proportion of breeding exclusively goat. This Saharan goat is a small ruminant with a black dress with white’s spots, hanging ears, and a coat more or less long. It is known for its hardiness and resistance to adverse conditions of arid zones and its perfect ecophysiological adaptation to harsh environmental conditions. However, pregnancy alterations, particularly abortion, degrade its productivity and cause economic losses, having both direct and indirect effects on animal production, like the costs of veterinary interventions and the reconstitution of livestock. The purpose of this work is to study the histological aspect of the liver of goats’ aborted living under nomadic herds in the region of Béni-Abbès (30° 7' N, 2° 10 'O). The organs were collected in physiological serum, rinsed, and then fixed with formaldehyde (37°, diluted at 10%). After that, these samples were processed for a topographic study. The morphometric study of the liver was performed by using an image analysis and processing software "Image J"; the various measurements obtained are intended to specify the supposed stage of development according to the body weight. The histological structure of the liver shows that the hepatic parenchyma consists of vascular conjunctive spaces surrounded by Glisson’s capsule. The sinusoids and hepatic portal vein are full of red blood cells, representing sinusoidal congestion and a thrombosed vein. At high magnification, the blood vessels show the presence of vascular thrombosis and haemorrhage in some areas of the hepatic parenchyma. Morphometric analysis shows that the number of liver parenchymal cells and the diameter of liver vessels vary according to the stage of development. The results obtained will provide details of the anatomical and cellular elements that can be used in the diagnosis of early or late abortion and late embryonic death. It would be interesting to find, by immunohistochemistry, some inflammatory markers useful for monitoring the progress of pregnancy and bioindicators of fetomaternal distress.

Keywords: aborting goat, arid zone, liver, histopathology

Procedia PDF Downloads 95

Authors: Anjana Aggarwal, Sheilja Walia

Abstract:

Prevalence of obesity and overweight is increasing due to sedentary lifestyles and busy schedules of people that spend less time on physical exercise. To reduce weight, people are finding easier and more convenient ways. The easiest solution is the use of dietary supplements and fat burners. These are products that decrease body weight by increasing the basal metabolic rate. Various reports have been published on the consumption of fat burners leading to heart palpitations, seizures, anxiety, depression, psychosis, bradycardia, insomnia, muscle contractions, hepatotoxicity, and even liver failure. Case reports and series are reporting that the ingredients present in the fat burners caused acute liver failure (ALF) and hepatic toxicity in many cases. Another contributing factor is the absence of regulations from the Food and Drug Administration on these products, leading to increased consumption and a higher risk of liver diseases among the population. This systematic review aims to attain a better understanding of the dietary supplements used globally to reduce weight and document the case reports/series of acute liver failure caused by the consumption of fat burners. Electronic databases like PubMed, Cochrane, Google Scholar, etc., will be systematically searched for relevant articles. Various websites of dietary products and brands that sell such supplements, Journals of Hepatology, National and international projects launched for ALF, and their reports, along with the review of grey literature, will also be done to get a better understanding of the topic. After discussing with the co-author, the selection and screening of the articles will be performed by the author. The studies will be selected based on the predefined inclusion and exclusion criteria. The case reports and case series that will be included in the final list of the studies will be assessed for methodological quality using the CARE guidelines. The results from this study will provide insights and a better understanding of fat burners. Since the supplements are easily available in the market without any restrictions on their sale, people are unaware of their adverse effects. The consumption of these supplements causes acute liver failure. Thus, this review will provide a platform for future larger studies to be conducted.

Keywords: acute liver failure, dietary supplements, fat burners, weight loss supplements

Procedia PDF Downloads 84

Authors: Deepak Nathiya1, Ramesh Roop Rai, Pratima Singh1, Preeti Raj1, Supriya Suman, Balvir Singh Tomar

Abstract:

Background: Sarcopenia is a catabolic state in liver cirrhosis (LC), accelerated with a breakdown of skeletal muscle to release amino acids which adversely affects survival, health-related quality of life, and response to any underlying disease. The primary objective of the study was to investigate the long-term effect of branched-chain amino acids (BCAA) supplementations on parameters associated with improved prognosis in sarcopenic patients with LC, as well as to evaluate its impact on cirrhotic-related events. Methods: We carried out a 24 week, single-center, randomized, open-label, controlled, two cohort parallel-group intervention trial comparing the efficacy of BCAA against lactoalbumin (L-ALB) on 106 sarcopenic liver cirrhotics. The BCAA (intervention) group was treated with 7.2 g BCAA per whereas, the lactoalbumin group was also given 6.3 g of L-Albumin. The primary outcome was to assess the impact of BCAA on parameters of sarcopenia: muscle mass, muscle strength, and physical performance. The secondary outcomes were to study combined survival and maintenance of liver function changes in laboratory and clinical markers in the duration of six months. Results: Treatment with BCAA leads to significant improvement in sarcopenic parameters: muscle strength, muscle function, and muscle mass. The total cirrhotic-related complications and cumulative event-free survival occurred fewer in the BCAA group than in the L-ALB group. Prognostic markers also improved significantly in the study. Conclusion: The current clinical trial demonstrated that long-term BCAAs supplementation improved sarcopenia and prognostic markers in patients with advanced liver cirrhosis.

Keywords: sarcopenia, liver cirrhosis, BCAA, quality of life

Procedia PDF Downloads 134

Authors: Sabika Rafiq, Rubaida Mehmood, Sajid Hussain, Atia Iqbal

Abstract:

Background and objectives: The pathogenesis of liver function abnormalities and cardiac dysfunction in hyperthyroid patients after I131 treatment is still unclear. This study aimed to determine the effects of radioiodine I131 on liver function parameters, lactate dehydrogenase (LDH) and low-density lipoproteins (LDL) before and after I131 therapy hyperthyroidism patients. Material & Methods: A total of 52 patients of hyperthyroidism recommended for I131were involved in this study with ages ranging from 12–65 years (mean age=38.6±14.8 & BMI=11.5±3.7). The significance of the differences between the results of 1st, 2nd and 3rd-time serum analysis was assessed by unpaired student’s t-test. Associations between the parameters were assessed by Spearman correlation analysis. Results: Significant variations were observed for thyroid profile free FT3 (p=0.04), FT4 (p=0.01), TSH (p=0.005) during the follow-up treatment. Before taking I131 (serum analyzed at 1st time), negative correlation of FT3 with AST (r=-0.458, p=0.032) and LDL (r=-0.454, p=0.039) were observed. During 2nd time (after stopping carbimazole), no correlation was assessed. Two months after the administration of I131 drops, a significant negative association of FT3 (r=-0.62, p=0.04) and FT4(r=-0.61, p=0.02) with ALB were observed. FT3(r=-0.82, p=0.00) & FT4 (r=-0.71, p=0.00) also showed negative correlation with LDL after I131 therapy. Whereas TSH showed significant positive association with ALB (r=0.61, p=0.01) and LDL (r=0.70, p=0.00) respectively. Conclusion: Current findings suggested that the association of TFTs with biochemical parameters in patients with goiter recommended for iodine therapy is an important diagnostic and therapeutic tool. The significant changes increased in transaminases and low-density lipoprotein levels after taking I131drops are alarming signs for heart and liver function abnormalities and warrant physicians' attention on an urgent basis.

Keywords: hyperthyroidism, carbimazole, radioiodine I131, liver functions, low-density lipoprotein

Procedia PDF Downloads 154

Authors: Mateusz Bilski, Jakub Klas, Emilia Kowalczyk, Sylwia Koziej, Katarzyna Kulszo, Ludmiła Grzybowska- Szatkowska

Abstract:

Background: Liver metastases are a common complication of primary solid tumors and sig-nificantly reduce patient survival. In the era of increasing diagnosis of oligometastatic disease and oligoprogression, methods of local treatment of metastases, i.e. MDT, are becoming more important. Implementation of such treatment can be considered for liver metastases, which are a common complication of primary solid tumors and significantly reduce patient survival. To date, the mainstay of treatment for oligometastatic disease has been surgical resection, but not all patients qualify for the procedure. As an alternative to surgical resection, radiotherapy techniques have become available, including stereotactic body radiation therapy (SBRT) or high-dose interstitial brachytherapy (iBT). iBT is an invasive method that emits very high doses of radiation from the inside of the tumor to the outside. This technique provides better tumor coverage than SBRT while having little impact on surrounding healthy tissue and elim-inates some concerns involving respiratory motion. Methods: We conducted a systematic re-view of the scientific literature on the use of brachytherapy in the treatment of liver metasta-ses from 2018 - 2023 using PubMed and ResearchGate browsers according to PRISMA rules. Results: From 111 articles, 18 publications containing information on 729 patients with liver metastases were selected. iBT has been shown to provide high rates of tumor control. Among 14 patients with 54 unresectable RCC liver metastases, after iBT LTC was 92.6% during a median follow-up of 10.2 months, PFS was 3.4 months. In analysis of 167 patients after treatment with a single fractional dose of 15-25 Gy with brachytherapy at 6- and 12-month follow-up, LRFS rates of 88,4-88.7% and 70.7 - 71,5%, PFS of 78.1 and 53.8%, and OS of 92.3 - 96.7% and 76,3% - 79.6%, respectively, were achieved. No serious complications were observed in all patients. Distant intrahepatic progression occurred later in patients with unre-sectable liver metastases after brachytherapy (PFS: 19.80 months) than in HCC patients (PFS: 13.50 months). A significant difference in LRFS between CRC patients (84.1% vs. 50.6%) and other histologies (92.4% vs. 92.4%) was noted, suggesting a higher treatment dose is necessary for CRC patients. The average target dose for metastatic colorectal cancer was 40 - 60 Gy (compared to 100 - 250 Gy for HCC). To better assess sensitivity to therapy and pre-dict side effects, it has been suggested that humoral mediators be evaluated. It was also shown that baseline levels of TNF-α, MCP-1 and VEGF, as well as NGF and CX3CL corre-lated with both tumor volume and radiation-induced liver damage, one of the most serious complications of iBT, indicating their potential role as biomarkers of therapy outcome. Con-clusions: The use of brachytherapy methods in the treatment of liver metastases of various cancers appears to be an interesting and relatively safe therapeutic method alternative to sur-gery. An important challenge remains the selection of an appropriate brachytherapy method and radiation dose for the corresponding initial tumor type from which the metastasis origi-nated.

Keywords: liver metastases, brachytherapy, CT-HDRBT, iBT

Procedia PDF Downloads 113

Authors: Justina I. R. Udotong, Essien U. Essien

Abstract:

Diagnostic enzymes like aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were determined as indices of heavy metal pollution in Tilapia guinensis. Three different sets of fishes treated with lead (Pb), iron (Fe) and copper (Cu) were used for the study while a fourth group with no heavy metal served as a control. Fishes in each of the groups were exposed to 2.65 mg/l of Pb, 0.85 mg/l of Fe and 0.35 mg/l of Cu in aerated aquaria for 96 hours. Tissue fractionation of the liver tissues was carried out and the three diagnostic enzymes (AST, ALT, and ALP) were estimated. Serum levels of the same diagnostic enzymes were also measured. The mean values of the serum enzyme activity for ALP in each experimental group were 19.5±1.62, 29.67±2.17 and 1.15±0.27 IU/L for Pb, Fe and Cu groups compared with 9.99±1.34 IU/L enzyme activity in the control. This result showed that Pb and Fe caused increased release of the enzyme into the blood circulation indicating increased tissue damage while Cu caused a reduction in the serum level as compared with the level in the control group. The mean values of enzyme activity obtained in the liver were 102.14±6.12, 140.17±2.06 and 168.23±3.52 IU/L for Pb, Fe and Cu groups, respectively compared to 91.20±9.42 IU/L enzyme activity for the control group. The serum and liver AST and ALT activities obtained in Pb, Fe, Cu and control groups are reported. It was generally noted that the presence of the heavy metal caused liver tissues damage and consequent increased level of the diagnostic enzymes in the serum.

Keywords: diagnostic enzymes, enzyme activity, heavy metals, tissues investigations

Procedia PDF Downloads 287

Authors: Hanen Bouaziz-Ketata, Ghada Ben Salah, Hichem Ben Salah, Kamel Jamoussi, Najiba Zeghal

Abstract:

The present study investigated the protective role of Hyparrhenia hirta on nitrate-induced liver damage. Experiments were carried out on adult rats divided into 3 groups, a control group and two treated groups. NaNO3 was administered daily by oral gavage at a dose of 400 mg/kg bw in treated groups either alone or coadministered with Hyparrhenia hirta methanolic extract via drinking water at a dose of 200 mg/kg bw for 50 days. Liver toxicity induced by NaNO3 was characterized by higher serum levels of glucose, total cholesterol and triglyceride and lower serum total protein than those of controls. Transaminases and lactate deshydrogenase activities in serum were elevated indicating hepatic cells’ damage after treatment with NaNO3. The hyperbilirubinemia and the increased serum gamma glutamyl transferase activities suggested the presence of cholestasis in NaNO3 exposed rats. In parallel, NaNO3 caused oxidant/antioxidant imbalance in the liver as reflected by the increased lipid peroxidation, the decreased total glutathione content and superoxide dismutase, catalase and glutathione peroxidase activities. Nitrate caused also a significant induction of DNA fragmentation as evidenced by the presence of a smear without ladder formation on agarose gel. Hyparrhenia hirta supplementation showed an improvement of all parameters cited above. We conclude that the present work provides ethnopharmacological relevance of Hyparrhenia hirta against the toxic effect of nitrate, suggesting its role as a potential antioxidant.

Keywords: Hyparrhenia hirta, liver, nitrate toxicity, oxidative stress, rat

Procedia PDF Downloads 543

Authors: Fatimah A. Alhomaid

Abstract:

The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of liver cancer in Saudi patients. our results were carried out on 54 patients liver cancer. We obtained our data from laboratory in King Khalid University Hospital. The specimens were taken (54) patients with liver cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as grade I in tow patients (male and female) and grade 2 in 45 patients (28 male and 17 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining, immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients with adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscular layer. With advancing the disease, there were haemorrhage in blood and increase in lymphocytes and increase in the number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20, PCNA, P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for PCAN and the grades. In our sections there were strong reaction in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of liver cancer.

Keywords: cancer, CK20, DNA, cytometry analysis, liver, immunohistochemical, molecular changes, PCNA, p53

Procedia PDF Downloads 264

Authors: Ezomoh O. Olubunmi, Chukwuma S. Anakwe, Bekewei Progress, Prohp The Prophet

Abstract:

Benzene is a volatile organic compound that is recognised as carcinogenic to humans. The objective of the current investigation was to ascertain the impact of the administration of benzene at varying concentrations on the livers of Wistar rats. The 40 adult female Wistar rats were divided into 10 groups, each consisting of four rats. For 28 days, Group 1 received distilled water, while Groups 2 to 10 were administered 0.04,0.06,0.08,0.2,0.4,0.6,0.8,1.0, and 1.2 ml/kg body weight of analytical grade benzene. Blood samples were obtained through cardiac puncture for liver function assessment, while the animals in groups 1 to 5 were euthanised after the 28th day under chloroform anaesthesia. The animals in groups 6 to 10 died midway through the study period. Antioxidant analysis was conducted on liver tissues that were collected and homogenised. The results indicated a substantial (p<0.05), dose-dependent increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities as a result of benzene exposure. Additionally, benzene resulted in a substantial reduction in the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in liver tissue, as well as an increase in malondialdehyde (MDA) concentrations, and this effect was dose-dependent. These findings emphasise the hepatotoxic effects of benzene, even at concentrations that are relatively low.

Keywords: benzene, alanine aminotransferase, aspartate aminotransferase, alkaline phosphate, antioxidants, superoxide dismutase, catalase, glutathione peroxidase

Procedia PDF Downloads 19

Authors: Faris Alkhalil, Rana Bitar, Amer Azaz, Hisham Natour, Noora Almeraikhi, Mohamad Miqdady

Abstract:

Background: Children with liver transplantation are achieving very good survival and so there is now a need to concentrate on achieving good health in these patients and preventing disease. Immunosuppressive medications have side effects that need to be monitored and if possible avoided. Glucocorticoids and calcineurin inhibitors are detrimental to bone and mineral homeostasis in addition steroids can also affect linear growth. Steroid sparing regimes in renal transplant children has shown to improve children’s height. Aim: We aim to review the growth and bone health of children post liver transplant by measuring bone mineral density (BMD) using dual energy X-ray absorptiometry (DEXA) scan and assessing if there is a clear link between poor growth and impaired bone health and use of long term steroids. Subjects and Methods: This is a single centre retrospective Cohort study, we reviewed the medical notes of children (0-16 years) who underwent a liver transplantation between November 2000 to November 2016 and currently being followed at our centre. Results: 39 patients were identified (25 males and 14 females), the median transplant age was 2 years (range 9 months - 16 years), and the median follow up was 6 years. Four patients received a combined transplant, 2 kidney and liver transplant and 2 received a liver and small bowel transplant. The indications for transplant included, Biliary Atresia (31%), Acute Liver failure (18%), Progressive Familial Intrahepatic Cholestasis (15%), transplantable metabolic disease (10%), TPN related liver disease (8%), Primary Hyperoxaluria (5%), Hepatocellular carcinoma (3%) and other causes (10%). 36 patients (95%) were on a calcineurin inhibitor (34 patients were on Tacrolimus and 2 on Cyclosporin). The other three patients were on Sirolimus. Low dose long-term steroids was used in 21% of the patients. A considerable proportion of the patients had poor growth. 15% were below the 3rd centile for weight for age and 21% were below the 3rd centile for height for age. Most of our patients with poor growth were not on long term steroids. 49% of patients had a DEXA scan post transplantation. 21% of these children had low bone mineral density, one patient had met osteoporosis criteria with a vertebral fracture. Most of our patients with impaired bone health were not on long term steroids. 20% of the patients who did not undergo a DEXA scan developed long bone fractures and 50% of them were on long term steroid use which may suggest impaired bone health in these patients. Summary and Conclusion: The incidence of impaired bone health, although studied in limited number of patients; was high. Early recognition and treatment should be instituted to avoid fractures and improve bone health. Many of the patients were below the 3rd centile for weight and height however there was no clear relationship between steroid use and impaired bone health, reduced weight and reduced linear height.

Keywords: bone, growth, pediatric, liver, transplantation

Procedia PDF Downloads 278

Authors: Deepak Mohan, Sushma Sharma

Abstract:

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are a group of widely used drugs for the treatment of rheumatoid diseases and to relieve pain and inflammation due to their analgesic anti-pyretic and anti-inflammatory properties. The therapeutic and many of the toxic effects of NSAIDs result from reversible inhibition of enzymes in the cyclooxygenase (COX) group. In the present investigation the effect of the drug on the concentration of lipids, and on the activity of the enzymes i.e. acid and alkaline phosphatase, GOT, GPT and lipid peroxidase were studied. There was a significant enhancement in the activities of both acid and alkaline phosphatase after 21 days of treatment. Proportionate increase in the MDA contents was observed after different days of diclofenac treatment. Cellular damage in the liver resulted in decrease in the activity of both GOT (Glutamate oxaloacetate transaminase) and GPT (Glutamate pyruvate transaminase) in both low and high dose groups. Significant decrease in the liver contents was also observed in both dose groups.

Keywords: anti-inflammatory, cyclooxygenase, glutamate oxaloacetate transaminase, malondialdehyde

Procedia PDF Downloads 299

Authors: Bouzidi Abdelouahab, Ghadjati Nadhra, Bettihi Sara, Mahdeb Nadia, Daamouche Z. El Youm

Abstract:

The effects of acute administration of TOTAL alkaloids, the main active principle of Datura stramonium, with toxic properties, were studied in female Albino-Wistar rats. After acute intraperitoneal administration of dose 120 mg kg-1 (≈1/3 DL50) of total alkaloids to the seeds of D. stramonium, there were no remarkable changes in general appearance and no deaths occurred in any experimental group. After 5 days a significant reduction was observed in total alkaloids of seeds. The Red Blood Cells (RBC), Hematocrit (HCT) and Hemoglobin (HGB) show significant changes in the treated groups. There were no statistical differences in Glutamic-pyruvic Transaminase (GPT), Alkaline Phosphatase (ALP), urea, glucose and total protein observed between groups. After 24 h Glutamic-Oxaloacetic Transaminase (GOT) and creatinine were significantly higher in the treated male rats than the control group histological examination of liver showed no histopathological changes.

Keywords: datura stramonium, rat, liver, kidney, alkaloids, toxicity

Procedia PDF Downloads 481

Authors: M. Chaichanyut, S. Tungjitkusolmun

Abstract:

This paper is concerned with microwave (MW) ablation for a liver cancer tissue by using helix antenna. The antenna structure supports the propagation of microwave energy at 2.45 GHz. A 1½ turn spiral catheter-based microwave antenna applicator has been developed. We utilize the three-dimensional finite element method (3D FEM) simulation to analyze where the tissue heat flux, lesion pattern and volume destruction during MW ablation. The configurations of helix antenna where Helix air-core antenna and Helix Dielectric-core antenna. The 3D FEMs solutions were based on Maxwell and bio-heat equations. The simulation protocol was power control (10 W, 300s). Our simulation result, both helix antennas have heat flux occurred around the helix antenna and that can be induced the temperature distribution similar (teardrop). The region where the temperature exceeds 50°C the microwave ablation was successful (i.e. complete destruction). The Helix air-core antenna and Helix Dielectric-core antenna, ablation zone or axial ratios (Widest/length) were respectively 0.82 and 0.85; the complete destructions were respectively 4.18 cm³ and 5.64 cm³.

Keywords: liver cancer, Helix antenna, finite element, microwave ablation

Procedia PDF Downloads 307

Authors: Angelis P. Barlampas

Abstract:

PURPOSE: The purpose of this paper is to demonstrate the important role of taking an appropriate and detailed history, in order to reach the best possible diagnostic conclusion. MATERIAL: A patient presented to the emergency department due to the sudden onset of continuous abdominal pain, during the last hour and with the clinical symptoms of an acute abdomen. During the clinical examination, signs of peritoneal irritation and diffuse abdominal tenderness were found. The rest of the clinical and laboratory tests did not reveal anything important. From the reported medical history, nothing of note was found, except for the report of a large liver cyst, for which he was advised not to take any further action, except from regular ultrasound examination . METHOD: A computed tomography examination was performed after per os administration of gastrografin, which revealed a hyperdense ascitic effusion, similar in density to that of gastrografin within the intestinal tract. The presence of a large cyst of the left hepatic lobe was confirmed, contacting and pushing against the stomach. In the area of the contact between the liver cyst and the pylorus, there were extraluminal air bubbles and local opacity of the peritoneal fat, with a small hyperdense effusion. Result : The above, as well as the absence of a history of stomach ulcer or recent trauma, or other pathology, argue in favor of acute pyloric perforation, due to mural necrosis, in response to chronic external pressure from the pre-existing large liver cyst.

Keywords: perforation, stomach, large liver cyst, CT abdomen, acute abdominal pain, intraperitoneal leakage, constrast leakage

Procedia PDF Downloads 94

Authors: I. M. Fakai, A. Abdulhamid, I. Sani, F. Bello, E. O. Olusesi

Abstract:

The phytochemical screening and hepatotoxic effect of Datura metel aqueous seeds extract in Albino Wistar rats were evaluated. Phytochemicals were screened using standard methods. The enzymes activity and liver function indices were also determined using standard methods of analysis. The phytochemicals screening revealed the presence of alkaloid, tannin, glycoside and flavonoid. The organ-body weight decreased significantly (P<0.05) at all the doses of the extract treated groups compared to the control. The activity of alkaline phosphatase decreased significantly (P<0.05) in the liver and increased significantly in the serum at all the doses of the extract treated groups compared to the control. The activity of serum alanine transaminase increased significantly (P<0.05) while there is no significant difference (P>0.05) in the activity liver alanine transaminase at all the doses of the extract treated groups compared to the control. The result also revealed significant increase (P<0.05) in the aspartate transaminase activity in both liver and serum at all doses of the extract treated groups compared to the control. Serum total protein, albumin, globulin, and total bilirubin concentration decreased significantly (P<0.05), while direct bilirubin concentration increased significantly (P<0.05) at all the doses of the extract treated groups compared to the control. The present study therefore revealed that, the present of some phytochemicals in the plant extract attributed the plant to its hepatotoxic effects as revealed in the alteration of marker enzymes and some liver function indices analyzed.

Keywords: datura metel, transaminases, hepatotoxic effect, phytochemicals, rats

Procedia PDF Downloads 443

Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

Abstract:

Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

Procedia PDF Downloads 428

Authors: Aniekan Peter, ECS Naidu, Edidiong Akang, U. Offor, R. Kalhapure, A. A. Chuturgoon, T. Govender, O. O. Azu

Abstract:

Introduction: Nano-drugs are novel innovations in the management of human immunodeficiency virus (HIV) pandemic, especially resistant strains of the virus in their sanctuary sites: testis and the brain. There are safety concerns to be addressed to achieve the full potential of this new drug delivery system. Aim of study: Our study was designed to investigate toxicity profile of Tenofovir Nanoparticle (TDF-N) synthesized by University of Kwazulu-Natal (UKZN) Nano-team for prevention and treatment of HIV infection. Methodology: Ten adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit UKZN were used for the study. The animals were weighed and divided into two groups of 5 animal each. Control animals (A) were administered with normal saline. Therapeutic dose (4.3 mg/kg) of TDF-N was administered to group B. At the end of four weeks, animals were weighed and sacrificed. Liver and kidney were removed fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT), liver function test (LFT) and full blood count (FBC) using appropriate analysers. Cellular measurements were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, values < 0.05 were significant. Results: We reported no histological alterations in the liver, kidney, FBC, LFT and RFT between the TDF-N animals and saline control. There were no significant differences in weight, organo-somatic index and histological measurements in the treatment group when compared with saline control. Conclusion/recommendations: TDF-N is not toxic to the liver, kidney and blood cells in our study. More studies using human subjects is recommended.

Keywords: tenofovir nanoparticles, liver, kidney, blood cells

Procedia PDF Downloads 182

Authors: Abhishek Kumar Jain, Anki Jain, Yuvraj Singh Dangi, Brajesh Kumar Tiwari

Abstract:

The plant Eclipta alba Hassk. (Family: Compositae) contains coumestans (wedelolactone and demethyl wedelolactone) used in liver disorders. The objective of the present investigation was to develop a formulation of these coumestans in combination with the soya phosphatidylcholine (PC), in order to overcome the limitation of absorption and to investigate the protective effect of coumestans–phosphatidylcholine complex (C-PC) on carbon tetrachloride induced acute liver damage in rats. Methanolic extract (ME) of the whole plant of Eclipta alba was fractionated with water and then with ehylacetate. Coumestans were characterized in the ethylacetate fraction of methanolic extract (EFME). The C-PC was prepared by dissolving EFME and PC in 1:1 ratio in dichloromethane and heating at 60°C for 2 h. The C-PC was characterized by DSC and FTIR spectroscopy. In vitro drug release from EFME and C-PC through egg membrane was measured using UV-Visible spectrophotometer. The hepatoprotective activity of C-PC (equivalent to 5.35 and 10.7 mg/kg body weight of EFME), ME 250 mg/kg and EFME 5.35 mg/kg was evaluated by measuring various enzymes level. C-PC significantly provided better protection to the liver by restoring the enzyme levels of SGPT, SGOT, ALP and total billirubin with respect to carbon tetrachloride (CCl4) treated group (P < 0.001). Histopathological studies were also performed. The C-PC provided better protection to rat liver than ME and EFME at similar doses as well as shown significant regeneration of hepatocytes, central vein, intact cytoplasm, and nucleus.

Keywords: hepatotoxicity, wedelolactone, soya phosphatidylcholine, eclipta alba

Procedia PDF Downloads 403

Authors: Marwa M. Abu-Serie, Marwa M. Eltarahony

Abstract:

The search for reliable, effective, and safe nanoparticles (NPs) as a treatment for cancer is a pressing priority. In this study, Cu-NPs were fabricated by Streptomyces cyaneofuscatus through simultaneous bioreduction strategy of copper nitrate salt. The as-prepared Cu-NPs subjected to structural analysis; energy-dispersive X-ray spectroscopy, elemental mapping, X-ray diffraction, transmission electron microscopy, and ζ-potential. These biological synthesized Cu-NPs were mixed with disulfiram (DS), forming a nanocomplex of Cu-DS with a size of ~135 nm. The prepared nanocomplex (nanoCu-DS) exhibited higher anticancer activity than that of free complex of DS-Cu, Cu-NPs, and DS alone. This was illustrated by the lowest IC50 of nanoCu-DS (< 4 µM) against human breast and liver cancer cell lines comparing with DS-Cu, Cu-NPs, and DS (~8, 22.98-33.51 and 11.95-14.86, respectively). Moreover, flow cytometric analysis confirmed that higher apoptosis percentage range of nanoCu-DS-treated in MDA-MB 231, MCF-7, Huh-7, and HepG-2 cells (51.24-65.28%) than free complex of Cu-DS ( < 4.5%). Regarding inhibition potency of liver and breast cancer cell migration, no significant difference was recorded between free and nanocomplex. Furthermore, nanoCu-DS suppressed gene expression of β-catenine, Akt, and NF-κB and upregulated p53 expression (> 3, >15, > 5 and ≥ 3 folds, respectively) more efficiently than free complex (all ~ 1 fold) in MDA-MB 231 and Huh-7 cells. Our finding proved this prepared nano complex has a powerful anticancer activity relative to free complex, thereby offering a promising cancer treatment.

Keywords: biologically prepared Cu-NPs, breast cancer cell lines, liver cancer cell lines, nanoCu- disulfiram

Procedia PDF Downloads 186

Authors: Shenghu Feng, Jun Cheng

Abstract:

The molecular mechanism underlying nonalcoholic fatty liver disease (NAFLD) progression to hepatocellular carcinoma (HCC) remains unknown. In this study, immunohistochemistry staining result showed that NS5ABP37 protein expression decreased as with increasing degree of HCC malignancy. In agreement, NS5ABP37 protein overexpression significantly suppressed cell proliferation, caused G1/S cell cycle arrest, and induced apoptosis by increasing caspase-3/7 activity and cleaved caspase-3 levels. In addition, NS5ABP37 overexpression resulted in decreased intracellular TG and TC contents, with level reduction in SREBPs and downstream effectors. Furthermore, NS5ABP37 overexpression decreased SREBP1c and SREBP2 levels by inducing their respective promoters. Finally, ROS levels and ER-stress were both induced by NS5ABP37 overexpression. These findings together demonstrate that NS5ABP37 inhibits cancer cell proliferation and promotes apoptosis, by altering SREBP-dependent lipogenesis and cholesterogenesis in HepG2 cells and inducing oxidative stress and ER stress.

Keywords: NS5ABP37, liver cancer, lipid metabolism, oxidative stress, ER stress

Procedia PDF Downloads 152

Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

Abstract:

Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

Procedia PDF Downloads 164

Authors: Keivan Jamshidi, Afshin Zahedi

Abstract:

An abattoir based study was carried out during spring 2011 to investigate pathological conditions of the liver in camels (Camelus deromedarius) slaughtered in the Semnan slaughter house, Northern East of Iran. In this study, 40 carcasses out of 150 randomly selected carcasses inspected at postmortem, found with liver lesions. Proper tissue samples obtained from the livers with macroscopic lesions, fixed in 10% neutral buffer formaldehyde, processed for routine histopathological techniques, and finally embedded in paraffin blocks. Sections of 5µm thickness then cut and stained by H&E staining techniques. In histopathological examination of hepatic tissues, following changes were observed: Hydatid cysts; 65%, Cirrhosis; 10%, Hepatic lipidosis (Mild to Severe fatty changes); 12.5%, Glycogen deposition; 2.5%, Cholangitis; 2.8%, Cholangiohepatitis; 5%, Calcified hydatid cyst; 2.5%, Hepatic abscess; 2.5%, lipofuscin pigments; 17.5%. It is concluded that the highest and lowest prevalent patterns of hepatic lesions were hydatid cysts and Hepatic abscess respectively.

Keywords: camel, liver, lesion, pathology, slaughterhouse

Procedia PDF Downloads 477