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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: 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: cancer,chemotherapy,amino acid,hepatotoxicity,Hepatoprotection,Drug-Induced Liver Injury (DILI)
- چکیده:
- چکیده انگلیسی: Taurine (2-aminoethane sulfonic acid) is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid) is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 µM, 100 µM and 1000 µM) of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5‑Fluorouracil, Doxorubicin and Dacarbazine) via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+). Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione) were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug‑treated livers. It was found that taurine (5 and 10 mM) and glycine (5 and 10 mM) administration significantly mitigated the biomarkers of liver injury and attenuated drug‑induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.
- انتشار مقاله: 12-10-1394
- نویسندگان: Reza Heidari,Akram Jamshidzadeh,Hossein Niknahad,Farshad Safari,Hamdollah Azizi,Narges Abdoli,Mohammad Mehdi Ommati,Forouzan Khodaei,Arastoo Saeedi,Asma Najibi
- مشاهده