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کاربرد نوع شرط:
- 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
- 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
- جایگاه : پژوهشی
- مجله: Trends in Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Medicinal plants,Hepatoprotective,hepatotoxicity,Liver injury,Gundelia tournefortii
- چکیده:
- چکیده انگلیسی: Xenobiotics-induced liver injury is a major challenge for clinicians and pharmaceutical industry. Hence, finding new therapeutic molecules against this complication has clinical value. The current investigation aimed to evaluate the potential protective effects of different fractions obtained from Gundelia tournefortii (GT) hydroalcoholic extract in a rat model of acute hepatic injury. Male Sprague-Dawley rats (200‑250 g) were treated with carbon tetrachloride (CCl4) (1.5 ml/kg, i.p), then ethanol, water, chloroform, ethyl acetate, and n-Butanol fractions of GT extract were administered. Biochemical and histopathological markers of hepatic injury were assessed and glutathione (GSH) and lipid peroxidation were monitored in liver samples. CCl4 administration caused hepatotoxicity as revealed by an increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activity, as well as pathological changes of the liver. Furthermore, a significant reduction in hepatic glutathione content and an elevation in lipid peroxidation were observed in CCl4‑treated rats. It was found that the n‑butanol (200 mg/kg) and the ethyl acetate (300 mg/kg) fractions of GT extract protected liver against CCL4‑induced damage as judged by lower AST, ALT, LDH and lipid peroxidation, prevention of tissue glutathione depletion, and alleviation of histopathological damages of liver in extract‑treated animals. As n‑butanol and the ethyl acetate fractions of GT effectively alleviated the liver injury induced by CCl4 and provide antioxidant properties, we might be able to propose that the hepatoprotective chemicals of Gundelia extract are present in these fractions.
- انتشار مقاله: 12-10-1394
- نویسندگان: Hossein Niknahad,Reza Heidari,Tannaz Mokhtebaz,Sasan Mansouri,Shadab Dehshahri,Narges Abdoli,Asma Najibi
- مشاهده