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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Trends in Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Antioxidant,Stress,Surgery,mitochondrion,Energy crisis
- چکیده:
- چکیده انگلیسی: Surgery-associated small intestine damage is a clinical complication. It has been found that opening the abdominal cavity during surgery and manipulation of organs, including the intestine, could lead to intestinal barrier disintegrity and the entrance of pathogens to the systemic circulation. Hence, finding agents to protect the intestine during surgical manipulation could have clinical value. Oxidative stress and enterocytes mitochondrial dysfunction and energy (ATP) crisis are the proposed mechanisms for surgery-induced intestinal damage. N-acetylcysteine (NAC) is a thiol reducing agent and radical scavenging molecule which is widely investigated for its pharmacological properties. The current study was designed to evaluate the effects of NAC treatment on the surgery-induced mitochondrial dysfunction in an animal model. Rats were treated with NAC (500 and 1000 mg/kg, oral) and underwent surgical stress. Afterward, the small intestine mitochondria were isolated and assessed. The effects of surgical stress on small intestine mitochondrial was revealed as a significant decrease in mitochondrial dehydrogenase activity, mitochondrial depolarization, decreased mitochondrial ATP levels, and mitochondrial permeabilization. Moreover, the level of alkaline phosphatase secretion from the intestinal brush border was increased. It was found that NAC treatment significantly alleviated ALP levels, and improved mitochondrial indices when this drug was pre-treated (1 week) to rats. Collectively, it could be concluded that NAC treatment might be a therapeutic approach against surgery-induced intestinal damage. The effects of NAC on mitochondrial function seem to has a pivotal role in its protective mechanism of action.
- انتشار مقاله: 16-01-1399
- نویسندگان: Reza Heidari,Khadijeh Mousavi,Shayesteh Amin,Mohammad Mehdi Ommati,Hossein Niknahad
- مشاهده
- جایگاه : پژوهشی
- مجله: Trends in Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: oxidative stress,Mitochondria,Liver failure,cholestasis,Bile Acids,Bioenergetics
- چکیده:
- چکیده انگلیسی: Different diseases or xenobiotics could cause cholestasis. The only promising treatment for this disease is the identification of its etiology or liver transplantation in severe cases. Nevertheless, preserving liver function could delay organ injury or help to the treatment of the disease in mild cases. The mechanism of cholestasis-induced liver injury is multifactorial. However, it has been found that hepatocyte mitochondrial function is impaired in this disease. Methylene blue (MB) is a phenothiazine compound. MB is pharmacologically used for a wide range of diseases. It has been found that this compound could significantly improve mitochondrial function and prevent the releases of cell death mediators from this organelle. MB is also well-known for its preventing effect on mitochondria-facilitating reactive oxygen species (ROS) formation. It has been found that mitochondrial function is impaired in the liver tissue in different models of cholestasis. The current study aimed to evaluate the effects of MB administration on mitochondrial indices in cholestatic animals. Rats underwent bile duct ligation (BDL) surgery and treated with MB (0.5 and 1 mg/kg, oral). Significant mitochondrial permeabilization, mitochondrial membrane depolarization, lipid peroxidation, decreased mitochondrial dehydrogenase activity, and depleted ATP content was evident in BDL rats. It was found that mitochondrial indices improved in MB-treated cholestatic animals. Based on the data collected in this study, MB might be useful as a therapeutic agent in cholestasis. The mitochondria protecting properties of this compound could play a major role in its mechanism of action.
- انتشار مقاله: 16-01-1399
- نویسندگان: Reza Heidari,Asrin Ahmadi,Mohammad Mehdi Ommati,Hossein Niknahad
- 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: oxidative stress,amino acid,Nutraceuticals,Cytoprotection,Mitochondrial cytopathies
- چکیده:
- چکیده انگلیسی: Taurine (TAU) is the most abundant free amino acid in the human body. High concentrations of this amino acid are found in tissues such as the skeletal muscle, brain, and kidney. Recently, a focus has emerged on the effects of TAU on cellular mitochondria. It has been found that TAU could positively affect this organelle by enhancing mitochondrial membrane potential, increasing ATP levels, and mitigating mitochondria-mediated ROS formation. The current study aimed to evaluate the effect of a wide range of TAU concentrations (0.01 mM-1000 mM) on mitochondrial function. Mice liver mitochondria were isolated and exposed to different concentrations of TAU (30 min). Several indices, including mitochondrial depolarization, dehydrogenases activity, permeabilization, and ATP content, were monitored. It was found that TAU supplementation significantly enhanced parameters such as mitochondrial ATP levels and mitochondrial membrane potential in comparison with the control group. Moreover, TAU prevented Ca2+-induced mitochondrial permeabilization. This amino acid revealed no significant adverse effect on isolated mitochondria even at very high and supra-physiological concentrations (e.g., 100, 250, and 500 mM). These data suggest TAU as an ideal and safe agent to protect mitochondria against toxic insults or regulating cellular function in different mitochondria-linked disorders.
- انتشار مقاله: 21-08-1398
- نویسندگان: Hamidreza Mohammadi,Mohammad Mehdi Ommati,Omid Farshad,Akram Jamshidzadeh,Mohammad Reza Nikbakht,Hossein Niknahad,Reza Heidari
- مشاهده
- جایگاه : پژوهشی
- مجله: Trends in Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی:
- چکیده:
- چکیده انگلیسی: Carnosine is an abundantly found dipeptide present in different tissues. Several pharmacological properties have been attributed to carnosine. On the other hand, the precise mechanism of cytoprotection provided by carnosine remains obscure. The current study aimed to evaluate the direct effect of different concentrations of carnosine on cellular mitochondria as an essential target involved in the cytoprotection/cytotoxicity. Liver mitochondria were isolated and exposed to carnosine (0.01-20 mM). Mitochondrial depolarization, dehydrogenases activity, mitochondrial swelling and permeability, and ATP content were assessed. On the other hand, the effect of carnosine supplementation on calcium (Ca2+) overload-induced mitochondrial injury was evaluated. It was found that concentrations between 0.01-20 mM of this peptide preserved mitochondrial indices of functionality in a Ca2+ overloaded environment. These data represent regulation of mitochondrial function as a primary mechanism for the protective properties of carnosine.
- انتشار مقاله: 30-11-1396
- نویسندگان: Reza Heidari,Vahid Ghanbarinejad,Mohammad Mehdi Ommati,Akram Jamshidzadeh,Hossein Niknahad
- مشاهده
- جایگاه : پژوهشی
- مجله: Trends in Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی:
- چکیده:
- چکیده انگلیسی: The cholestatic liver disease ensues with a hepatic accumulation of cytotoxic molecules. Several hydrophobic bile acids are known as cytotoxic agents accumulated in the liver during cholestasis. Chenodeoxycholic acid (CDCA) is a toxic hydrophobic bile acid. Oxidative stress and mitochondrial dysfunction are well-known mechanisms of bile acids cytotoxicity. In the current study, CDCA effect on isolated liver mitochondria was monitored by analyzing the changes in mitochondrial dehydrogenases activity, mitochondrial permeabilization, and mitochondrial membrane potential. On the other hand, taurine (1 mM) and carnosine (1 mM) were added as potential protective agents against CDCA-induced mitochondrial dysfunction. Increasing concentrations of CDCA (100 µM - 1000 µM) impaired mitochondrial membrane potential, decreased mitochondrial dehydrogenases activity and enhanced mitochondrial permeabilization and swelling. It was found that taurine and carnosine supplementation preserved mitochondrial function in the presence of CDCA. The results mention that toxicologically relevant concentrations of CDCA impaired mitochondrial function. On the other hand, taurine and carnosine might be applicable as protective agents against bile acids-induced mitochondrial impairment and toxicity.
- انتشار مقاله: 12-03-1397
- نویسندگان: Reza Heidari,Narges Abdoli,Mohammad Mehdi Ommati,Akram Jamshidzadeh,Hossein Niknahad
- 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