Fatemeh Nabavizadeh

Protective effect of ghrelin on acetaminophen-induced liver injury in rat.

Ghrelin is a peptide that has protective effects on many tissues of the body. It has anti-inflammatory and anti-oxidant effects. Acetaminophen, a commonly used analgesic-antipyretic drug, has hepatotoxic side effects. The aim of this study was to evaluate the protective role of ghrelin in liver toxicity due to acetaminophen overdose. Thirty male rats were used in this study and divided into five groups. They were control, propylene-glycol (as a solvent of acetaminophen), acetaminophen, acetaminophen and NAC, acetaminophen and ghrelin groups. Tumor necrosis factor alpha (TNF-α), and hepatic enzymes, AST (aspartate aminotransferase) and ALT (alanine aminotransferase), were assessed and histologic study of liver were performed as indicators of liver damage following acetaminophen toxicity. Results showed that Ghrelin decreased ALT and AST to the normal level, and also reduced TNF-α. Although NAC (the standard antidote of acetaminophen toxicity) also reduced ALT, AST and TNF-α levels, our results show that ghrelin is more potent than NAC in protecting the liver from acetaminophen-induced liver injury.

Naltrexone attenuates endoplasmic reticulum stress induced hepatic injury in mice

Endoplasmic reticulum (ER) stress provides abnormalities in insulin action, inflammatory responses, lipoprotein B100 degradation and hepatic lipogenesis. Excess accumulation of triglyceride in hepatocytes may also lead to disorders such as non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Opioid peptides are involved in triglyceride and cholesterol dysregulation, inflammation and cell death. In this study, we evaluated Naltrexone effects on ER stress induced liver injury. To do so, C57/BL6 mice received saline, DMSO and Naltrexone, as control groups. ER stress was induced by tunicamycin (TM) injection. Naltrexone was given before TM administration. Liver blood flow and biochemical serum analysis were measured. Histopathological evaluations, TNF-α measurement and Real-time RT-PCR were also performed. TM challenge provokes steatosis, cellular ballooning and lobular inflammation which significantly reduced in Naltrexone treated animals. ALT, AST and TNF-α increased in the TM group and improved in the Naltrexone plus TM group. Triglyceride and cholesterol levels decreased in TM treated mice with no increase in Naltrexone treated animals. In the Naltrexone plus TM group, gene expression of Bax/Bcl-2 ratio and caspase3 significantly lowered compared with the TM group. In this study, we found that Naltrexone had a notable alleviating role in ER stress induced steatosis and liver injury.

Smart bomb AS1411 aptamer-functionalized/PAMAM dendrimer nanocarriers for targeted drug delivery in the treatment of gastric cancer

Chemotherapy, a conventional method assessed in recent oncology studies, poses numerous problems in the clinical environment. To overcome the problems inherent in chemotherapy, an intelligent drug delivery system has come to the forefront of cancer therapeutics. In this study, we designed a dendrimer‐based pharmaceutical system together with a single‐stranded AS1411 aptamer (APTAS1411) as a therapeutic strategy. The polyamidoamine (PAMAM)‐polyethylene glycol (PEG) complex was then conjugated with the AS1411 aptamer and confirmed by atomic‐force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) .In this study, we show that the conjugated PAMAM‐PEG‐APTAS1411complex dramatically increased PAMAM‐PEG‐5‐FU uptake by MKN45 gastric cancer cells. We also demonstrated both the stability of the nanoparticle‐5‐FU‐APTAS1411 complex, by thin layer chromatography (TLC), and an increase in 5‐fluorouracil (5‐FU) accumulation in the vicinity of cancerous tumors. This smart drug delivery system is capable of effectively transferring 5‐FU to MKN45 gastric cancer cells in consistent and without toxic effects.

Effect of different doses of GLP-2 (Teduglutide) on acute esophageal lesion due to acid-pepsin perfusion in male rats.

Gastro-esophageal reflux currently is widespread disorders with dangerous complications. GLP-2 is a peptide that has trophic and anti-inflammatory effects on gastrointestinal mucosa. The aim of this study was to evaluate the protective role of GLP-2 in esophageal mucosa lesion due to perfusion acid-pepsin. Thirty-six male rats were used in this study and divided into six groups. They were control, acid-pepsin, GLP-2 20 μg, GLP-2 30 μg, GLP-2 40 μg and GLP-2 50 μg/kg groups. Esophageal blood flow, plasma NO metabolite, esophageal tissue NO metabolites and histological study of esophagus were performed as indicators of esophageal damage following acid-pepsin perfusion. Results showed that GLP-2 significantly increased plasma and tissue NO metabolites in comparison to acid-pepsin group. Also histological study showed significantly fewer lesions in the most effective dose GLP-2 30 μg in comparison to acid-pepsin group, our results show that GLP-2 could be useful for the treatment of esophageal in animal model.

Naltrexone changes the expression of lipid metabolism-related proteins in the endoplasmic reticulum stress induced hepatic steatosis in mice

Endoplasmic reticulum (ER) stress is closely associated with several chronic diseases such as obesity, atherosclerosis, type 2 diabetes, and hepatic steatosis. Steatosis in hepatocytes may also lead to disorders such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), fibrosis, and possibly cirrhosis. Opioid peptides are involved in triglyceride and cholesterol dysregulation. Naltrexone also attenuates ER stress induced hepatic steatosis in mice. In this study, we evaluated the effects of naltrexone on the expression of lipid metabolism‐related nuclear factors and enzymes in the ER stress induced hepatic steatosis. C57/BL6 mice received saline, DMSO and naltrexone as control groups. In a fourth group, ER stress was induced by tunicamycin (TM) injection and in the last group, naltrexone was given before TM administration. Histopathological evaluations, real‐time RT‐PCR and western blot were performed. We found that GRP78, IRE1α, PERK and ATF6 gene expression and steatosis significantly reduced in naltrexone treated animals. Naltrexone alleviated the gene and protein expression of SREBP1c. Expression of ACAT1, apolipoprotein B (ApoB) and PPARα also increased after naltrexone treatment. In conclusion, this study, for the first time, shows that naltrexone has a considerable role in attenuation of ER stress‐induced liver injury.

Evaluation of nanocarrier targeted drug delivery of capecitabine-PAMAM dendrimer complex in a mice colorectal cancer model

Present study was focused to investigate the anti-hyperlipidemic activity of Terminalia bellerica against high fat diet induced hyperlipidemia and obesity. Terminalia bellerica commonly known as Baheda is one of the most common plants being used in India since early times in many disorders one of the ingredients in many polyherbal formulations like Triphala etc used for cardiac disorders. The ethanolic extract of the fruits of Terminalia bellerica 250mg/kg & 500mg/kg body weight was administered p.o. for 20 days to test antihyperlipidemic activity. The parameters for evaluation of anti-hyperlipidemic activity are the physical parameters and the biochemical estimations. The physical parameters were gross examination of heart, heart weight: body weight ratio, liver weight, atherogenic index and basal metabolic index. In biochemical estimations various cardiac enzymes like lactate dehydrogenase, and the lipid profile were measured. The results of present study show that alcoholic extract of Terminalia bellerica (500 mg/Kg) has significant reduction in various lipid levels as well as the elevated physical parameters like heart weight: body weight ratio, body weight gain and BMI against high fat diet induced hyperlipidemia and obesity compared to clinically used drugs, Atorvastatin (10mg/kg) and Orlistat (pure drug 10mg/kg).Capecitabine, an effective anticancer drug in colorectal cancer chemotherapy, may create adverse side effects on healthy tissues. In the present study, we first induced colon adenocarcinoma with azoxymethane, a carcinogen agent, and then investigated the potentiality of polyamidoamine (PAMAM) dendrimer to improve capecitabine therapeutic index and decrease its adverse side effects on healthy tissues like liver and bone marrow. Other variables such as nanoparticle concentrations have also been investigated. Drug loading concentration (DLC) and encapsulation efficiency (EE) were calculated for capecitabine/dendrimer complex. Experimental results showed an increase in DLC percentage resulted from elevated capecitabine/dendrimer ratio. Capecitabine/dendrimer complex could reduce tumor size and adverse side effects in comparison with free capecitabine form.The strategy of price liberalisation and privatisation had been implemented in Sudan over the last decade and has had a positive result on government deficit. The investment law approved recently has good statements and rules on the above strategy to pharmacy regulations. Under the pressure of the new privatisation policy, the government introduced radical changes in the pharmacy regulations. To improve the effectiveness of the public pharmacy, resources should be switched towards areas of need, reducing inequalities and promoting better health conditions. Medicines are financed either through cost sharing or full private. The role of the private services is significant. A review of reform of financing medicines in Sudan is given in this study. Also, it highlights the current drug supply system in the public sector, which is currently responsibility of the central medical supplies public corporation (CMS). In Sudan, the researchers did not identify any rigorous evaluations or quantitative studies about the impact of drug regulations on the quality of medicines and how to protect public health against counterfeit or low-quality medicines, although it is practically possible. However, the regulations must be continually evaluated to ensure the public health is protected against by marketing high quality medicines rather than commercial interests, and the drug companies are held accountable for their conduct.

Effect of opium dependency on secondary intention wound healing in a rat model: an experimental study

Opium dependency is a social and health problem in some middle eastern countries like Iran. Many of these people may require surgery. This study investigates the effects of opium dependency on histological parameters of secondary intention wound healing in rat. A full‐thickness wound (2 × 2 cm in diameters) was created on the dorsum of two groups of rats, a normal control group and a second group of rat depended to opium (Badawys method). Several times during 14 days postwounding, the wound was excised with peripheral margins of normal skin and was evaluated for cellular population, reepithelialisation and revascularisation. Results are presented as the mean ± standard error. Data were compared by an unpaired t‐test or analysis of variance. Histological examination of the wound tissue showed evidence of increased population of fibroblasts, decreased recruitment of neutrophile and plateau of macrophage cells in opium depended animals comparing with control group. In the depended animals, reepithelialisation was seen to be enhanced significantly, while prohibiting progression of revascularisation. This study shows that opium dependency enhances reepitheliazation as well as tissue recruitment of fibroblasts; thereby probable enhancement of secondary intention wound healing.