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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Trends in Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Mitochondria,weakness,Cirrhosis,Cell death,Energy crisis,Muscle waste
- چکیده:
- چکیده انگلیسی: Cirrhosis-associated muscle mass loss or sarcopenia is a common complication (17-30% prevalence) in cirrhotic patients. However, the pathogenesis of this complication is poorly understood. Therefore, finding the mechanisms of sarcopenia could lead to the development of therapeutic strategies against this complication. In the current study, rats underwent bile duct ligation (BDL) surgery, and their skeletal muscle (gastrocnemius; GS) was isolated and assessed 28 and 56 days after BDL operation. Significant increase in biomarkers of oxidative stress, including reactive oxygen species (ROS) formation, lipid peroxidation, and increased oxidized glutathione (GSSG) levels were detected in the muscle of cirrhotic animals. Skeletal muscle tissue antioxidant capacity and reduced glutathione (GSH) were also significantly decreased in BDL rats. Moreover, deterioration of several mitochondrial indices, including mitochondrial depolarization, increased mitochondrial permeabilization, depleted ATP reservoirs, and decreased mitochondrial dehydrogenases activity, were evident in the GS isolated from cirrhotic rats. Based on these data, oxidative stress and mitochondrial impairment seem to play as primary mechanisms of cirrhosis-induced sarcopenia.
- انتشار مقاله: 15-05-1399
- نویسندگان: Omid Farshad,Mohammad Mehdi Ommati,Jale Yüzügülen,Sahand Alizadeh,Khadijeh Mousavi,Negar Azarpira,Anahita Marhonian,Akram Jamshidzadeh,Reza Heidari
- مشاهده
- جایگاه : پژوهشی
- مجله: Trends in Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Neurodegeneration,oxidative stress,ATP,Neurotoxicity,Mitochondrial impairment
- چکیده:
- چکیده انگلیسی: Multiple sclerosis (MS) is a neurodegenerative disease. Although multiple factors are involved in the pathogenesis of MS, there are several lines of evidence that oxidative stress and mitochondrial dysfunction are involved in neuronal demyelination and deterioration of MS symptoms. Hence, compounds that could modulate mitochondrial function and decrease mitochondria-mediated ROS formation might be able to decrease MS symptoms. Methylene blue (MB) is a compound widely used in the treatment of central nervous system disease (e.g., Alzheimer's disease). It has been found that MB could robustly suppress mitochondria-mediated ROS formation at low concentrations. The current study was designed to evaluate the effect of MB on neuronal demyelination, mitochondrial function, and ROS formation in an animal model of MS. C57BL/6 male mice received cuprizone (0.1% w: w in chow diet for 42 consecutive days). MB (0.5 and 1 mg/kg, oral) was simultaneously administered. Significant demyelination was detected in CPZ-treated animals, which confirm the induction of MS in the mice model. Decreased animals’ locomotor activity, including significant suppression of open field movement, stride length, and decreased time on the rotarod, was evident in CPZ-treated mice. Mitochondrial indices, including significantly elevated lipid peroxidation, mitochondrial depolarization, significant mitochondrial permeabilization, and decreased ATP levels, were also detected in the CPZ group. It was found that MB administration significantly improved animals’ locomotor activity and mitochondrial indices in the current animal model of MS. The effects of MB on mitochondria and mitochondria-mediated ROS formation might play a fundamental role in the protective effects of this compound.
- انتشار مقاله: 10-12-1398
- نویسندگان: Mohammad Mehdi Ommati,Negar Azarpira,Forouzan Khodaei,Hossein Niknahad,Vahideh Gozashtegan,Reza Heidari
- مشاهده
- جایگاه : پژوهشی
- مجله: Trends in Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی:
- چکیده:
- چکیده انگلیسی: The liver is continuously exposed to a variety of xenobiotics. Several xenobiotics are identified which act as hepatotoxicants. Hence, finding protective agents for ameliorating xenobiotics-included liver injury has a great value. Eisenia foetida, a kind of “earthworm,” is a source of a wide range of bioactive components. Several investigations have been evaluated the E. foetida extract (EFX) for biomedical and nutritional applications. The current study was designed to evaluate the potential hepatoprotective properties of EFX in two experimental models of hepatic damage. Acetaminophen (APAP; 1 g/kg, i.p) was administered as the animal model of acute liver injury in mice. Bile duct ligated (BDL) rats were used as the animal model of chronic hepatic damage. Severe elevation in tissue biomarkers of oxidative stress including lipid peroxidation and hepatic glutathione depletion was evident in both APAP-treated and BDL animals. Moreover, serum biomarkers of liver injury were drastically increased in both acute and chronic animal models of hepatotoxicity. Significant liver tissue histopathological alterations including tissue necrosis, vascular congestion, and inflammatory cells infiltration were detected in APAP-treated and BDL animals. On the other hand, it was found that EFX supplementation (100, 200, 500, and 700 mg/kg, i.p) mitigated oxidative stress markers, decreased serum biomarkers of liver injury, and alleviated liver tissue histopathological changes. The hepatoprotection provided by EFX supplementation in the current study might be mediated through its potential antioxidative mechanisms.
- انتشار مقاله: 10-06-1397
- نویسندگان: Akram Jamshidzadeh,Fatemeh Dabagh,Omid Farshad,Mohammad Mehdi Ommat,Azadeh Mahdavinia,Negar Azarpira,Maryam Shahbazi,Asma Najibi,Reza Heidari
- مشاهده
- جایگاه : پژوهشی
- مجله: Trends in Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی:
- چکیده:
- چکیده انگلیسی: Hepatic encephalopathy (HE) is a serious clinical complication, which could lead to coma and death if not appropriately managed. There is agreement on the predominant role of ammonia in the etiology of HE. Brain is one of the most critical organs affected by ammonia. The critical role of oxidative stress and its consequences in the pathogenesis of ammonia-induced brain injury have been revealed before. On the other hand, there is no promising therapeutic option against ammonia neurotoxicity. Taurine is one of the most abundant amino acids in the human body. Several pharmacological roles including brain protecting properties have been attributed to this amino acid. The current study was designed to evaluate the role of taurine supplementation on HE-induced oxidative stress in the brain tissue. Animals received thioacetamide (400 mg/kg, i.p, for three consecutive days at 24-hr intervals) as a model of acute liver failure and hyperammonemia. Several serum biochemical parameters, in addition to plasma and brain ammonia level, were monitored. Moreover, markers of oxidative stress in the brain of hyperammonemic animals were assessed. It was found that plasma and brain ammonia was increased, and serum markers of liver injury were significantly elevated in the thioacetamide-treated group. On the other hand, an increase in markers of oxidative stress, including reactive oxygen species formation, lipid peroxidation, glutathione depletion, and decreased tissue antioxidant capacity, was detected in the brain tissue of thioacetamide-treated animals. It was found that taurine treatment (250, 500, and 1000 mg/kg, i.p) alleviated brain tissue markers of oxidative stress and decreased serum biomarkers of liver injury. Furthermore, lower plasma and brain ammonia were detected in taurine-treated animals. These data suggest taurine as a potential protective agent with therapeutic capability against HE-associated central nervous system complications.
- انتشار مقاله: 11-06-1396
- نویسندگان: Akram Jamshidzadeh,Narges Abdoli,Hossein Niknahad,Negar Azarpira,Elnaz Mardani,Somayeh Mousavi,Mojgan Abasvali,Reza Heidari
- مشاهده
- جایگاه : پژوهشی
- مجله: Trends in Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی:
- چکیده:
- چکیده انگلیسی: Fulminant hepatic failure is a deleterious clinical complication, which leads to hyperammonemia. Ammonia is a noxious neurotoxic agent, which affects brain tissue through different mechanisms. On the other hand, it is well-known that oxidative stress and its consequences play a major role in the pathogenesis of ammonia-induced brain injury. Carnosine is a dipeptide abundantly found in the human central nervous system (CNS). This peptide is widely investigated for its neuroprotective properties. The current study aimed to evaluate the effect of carnosine supplementation on oxidative stress markers in the brain tissue of a rat model of fulminant hepatic failure and hyperammonemia. Animals received thioacetamide (400 mg/kg, i.p, for three consecutive days at 24-hr intervals) as a model of acute liver failure and hyperammonemia. Several serum biochemical parameters, in addition to plasma and brain ammonia level, were monitored. On the other hand, brain tissue markers of oxidative stress including reactive oxygen species (ROS) formation, lipid peroxidation, tissue glutathione content, and total antioxidant capacity were measured. It was found that plasma and brain ammonia was increased, and serum markers of liver injury were significantly elevated in the thioacetamide-treated group. On the other hand, an increase in markers of oxidative stress, including ROS formation, lipid peroxidation, glutathione depletion, and decreased tissue antioxidant capacity, was evident in the brain of thioacetamide-treated animals. It was found that carnosine supplementation (250, 500, and 1000 mg/kg) decreased serum markers of liver injury, mitigated brain, and plasma ammonia level, and alleviated brain tissue markers of oxidative stress. These data suggest carnosine as a potential neuroprotective agent with therapeutic capability against ammonia-induced CNS injury.
- انتشار مقاله: 11-06-1396
- نویسندگان: Akram Jamshidzadeh,Narges Abdoli,Hossein Niknahad,Negar Azarpira,Somayeh Mousavi,Elnaz Mardani,Mojgan Abasvali,Reza Heidari
- مشاهده
- جایگاه : پژوهشی
- مجله: Trends in Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: chemotherapy,hepatotoxicity,Antineoplastic agents,Glutathione,Drug-Induced Liver Injury (DILI)
- چکیده:
- چکیده انگلیسی: Mitoxantrone is anthracycline antibiotic highly effective against various human cancers. Hepatotoxicity is associated with mitoxantrone administration. On the other hand, there is no effective therapeutic option against chemotherapy-induced liver injury. The current investigation was designed to evaluate the effect of thiol reductants on mitoxantrone-induced liver injury in two experimental models. As an ex vivo model, isolated rat liver was exposed to increasing concentrations of mitoxantrone (100, 250, 750, and 1000 µM) alone or in combination with thiol-reductants (Dithiothreitol; DTT, and N-acetyl cysteine; NAC). In addition, rats (in vivo) received mitoxantrone (2.5 mg/kg, i.p, at days 1, 10, and 20), NAC (100 and 300 mg/kg/day, i.p, for 20 consecutive days) and DTT (15 and 30 mg/kg/day, i.p, for 20 consecutive days), then liver and serum pathological changes were monitored. Mitoxantrone-induced liver injury was evident in both ex vivo and in vivo experiments as assessed by pathological changes in biomarkers of liver injury, along with tissue histopathological changes. Furthermore, an increase in liver tissue markers of oxidative stress was detected in the mitoxantrone-treated group. It was found that thiol reductants significantly mitigated mitoxantrone hepatotoxicity. The data indicate that thiol reductants might serve as hepatoprotective agents against chemotherapy-induced liver injury.
- انتشار مقاله: 11-02-1396
- نویسندگان: Hossein Niknahad,Helia Hosseini,Fatemeh Gozashtegan,Farzaneh Ebrahimi,Negar Azarpira,Narges Abdoli,Reza Heidari
- مشاهده
- جایگاه : پژوهشی
- مجله: Trends in Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: oxidative stress,Hepatoprotective,hepatotoxicity,Glutathione,Sodium Valproate
- چکیده:
- چکیده انگلیسی: Valproic acid (VPA) is a widely administered drug against epilepsy and several other neurological disorders. On the other hand, liver injury is a deleterious side effect associated with VPA. Oxidative stress seems to play a critical role in VPA-induced hepatotoxicity. The current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithiothreitol (DTT) as thiol reducing agents have any protective effects against VPA-induced liver injury. Isolated rat hepatocytes (in vitro) were exposed to increasing concentrations of VPA (25, 50, 100, 150, and 250 µM) and markers of cytotoxicity were evaluated. Furthermore, animals received VPA (250 and 500 mg/kg, i.p for 15 consecutive days) (in vivo) and markers of liver injury were monitored. It was found that 250 µM of VPA caused marked cytotoxicity toward isolated hepatocytes as judged by trypan blue exclusion test. Moreover, markers of oxidative stress including glutathione depletion and lipid peroxidation were detected in VPA-treated hepatocytes. On the other hand, VPA caused a significant increase in plasma markers of hepatotoxicity in drug-treated group. Liver histopathological changes and markers of oxidative stress were also detected in VPA-treated animals. It was found that administration of NAC (1 mM), and DTT (1 mM) significantly alleviated VPA-induced cytotoxicity (In vitro). NAC (250 and 500 mg/kg) and DTT (15 and 30 mg/kg) also significantly mitigated VPA hepatotoxicity (In vivo). The data obtained from the current investigation indicate potential therapeutic properties of thiol reductants against VPA-induced liver injury.
- انتشار مقاله: 11-02-1396
- نویسندگان: Nahid Najafi,Akram Jamshidzadeh,Hamideh Fallahzadeh,Mahmoud Omidi,Narges Abdoli,Asma Najibi,Negar Azarpira,Reza Heidari,Hossein Niknahad
- مشاهده
- جایگاه : پژوهشی
- مجله: Journal of Dentistry, Shiraz University of Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی:
- چکیده:
- چکیده انگلیسی: Statement of the Problem: Sinonasal papilloma (SNP) is a rare benign lesion characterized by high recurrence rate and malignant transformation. Purpose: This study aimed to investigate the prevalence of human papilloma virus (HPV) infection in these lesions in South of Iran. Materials and Method: In this cross sectional retrospective study, a total of 41 patients, 38 SNP and 3 SNP/Squamous cell carcinoma cases, from 2007 to 2014 were studied. Human papilloma virus (HPV) DNA detection was performed by nested PCR method and positive cases were analyzed for high risk HPV-16 and HPV-18. Results: HPV was detected in 31.7%; HPV- 16 in 4.9% and HPV 18 was not detected at all. Dysplastic epithelium was detected in 53% that was not associated with HPV. Three cases were accompanied with malignant transformation that HPV genome was detected in only one case and none of them were positive for HPV16 /18 genomic DNA. Conclusion: Current research suggests that HPV may be involved in the development of SNP. But the high risk HPV is not important in malignant transformation. More studies are needed to elucidate the possible etiologic mechanism between HPV, inverted papilloma, and squamous cell carcinoma. Keywords ● Sinonasal ● Papilloma ● Carcinoma ● Human papilloma virus ● High risk
- انتشار مقاله: 23-02-1395
- نویسندگان: Behnaz Valibeigi,Mohamad Javad Ashraf,Narges Kerdegari,Akbar Safai,Elham Abedi,Bijan Khademi,Negar Azarpira
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: WOUND HEALING,Nitric oxide,Sildenafil cream
- چکیده:
- چکیده انگلیسی: Nitric oxide (NO) is an important molecule synthesized during wound repair. Studies have reported the use of NO donors on cutaneous wound repair, but their effects in different phases of healing are not elucidated. The aim of this work was to investigate the effects of topical sildenafil on wounds in rats. Sildenafil (25 mg) was topically applied once daily on wound in treatment groups. On days, 7, 14 and 21 of lesion, five animals in each group were randomly selected and sacrificed and histological properties were evaluated. Our results showed the wound area contracted to 15% of the original size by day 7 post-wounding in treated group. Whereas control rats showed significantly delayed wound healing. The wound area contracted to 26% of the original size by day 14 post-wounding and to 46% by day 21 post-wounding. Also sildenafil cream caused more fibroblast and macrophage migration, increased vascularization, collagen regeneration, and epithelialization. This study indicates that sildenafil cream augments the wound healing process and may be of clinical benefit.
- انتشار مقاله: 19-04-1389
- نویسندگان: Akram Jamshidzadeh,Negar Azarpira
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Pathology
- نوع مقاله: Journal Article
- کلمات کلیدی: Squamous Cell Carcinoma,Human papilloma virus,tongue
- چکیده:
- چکیده انگلیسی: Background and objective: Oral tongue Squamous Cell carcinoma (SCC) commonly involves males between the sixth to eighth decades of life. Major risk factors are tobacco usage and alcohol consumption. The increasing number of patients developing oral tongue cancer without these well-known risk factors suggests that a viral infection, such as Human Papillomavirus (HPV), may be responsible for this increase, by acting as an oncogenic agent. This study investigated the prevalence of HPV infection and its clinicopathologic significance in oral tongue SCCs.
Material and methods: Tissue blocks from a total of 50 cases (patients with oral tongue SCC) and 50 controls (palatine tonsillar tissues with benign diagnosis) were selected. DNA was extracted from tumoral and non-tumoral tissue blocks. Detection of common HPV DNA by nested Polymerase Chain Reaction (PCR), and high-risk genotypes, HPV 16 and HPV 18, by conventional PCR, was achieved and the results correlated with clinicopathological parameters.
Results: Of the 50 patients (18 males and 32 females with a mean age of 57.36±12.18 years, and age range of 27 to 86 years), 7 (14%) had HPV positive results. None of the control group subjects had HPV DNA positive results (P-value of 0.012). The HPV genotype 16/18 was not detected in positive cases. No statistically significant association was found between HPV status and gender, age, tumor grade, tumor stage or lymph node involvement.
Conclusion: Although there was a significantly higher prevalence of HPV in oral tongue SCC, its association with carcinogenesis in this area requires further studies.- انتشار مقاله: 24-03-1395
- نویسندگان: Mohamad Javad Ashraf,Shahla Hosseini,Ahmad Monabati,Behnaz Valibeigi,Bijan Khademi,Elham Abedi,Negar Azarpira
- مشاهده