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کاربرد نوع شرط:
- 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
- جایگاه : پژوهشی
- مجله: Iranian Journal of Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی:
- چکیده:
- چکیده انگلیسی:
- انتشار مقاله: 14-04-1393
- نویسندگان: Soheila Khabbaz Azar,Mahmood Reza Moeen,Hossein Niknahad
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Hepatoprotective,Carbon tetrachloride,Punica granatum,HepG2 cells
- چکیده:
- چکیده انگلیسی: Punica granatum is used as a medicinal plant, and its fruit concentrate has been used for the prevention and treatment of liver diseases in Iran. The effects of different concentrations of the hydroalcoholic, ethyl acetate and n-hexane extracts of the Punica granatum (fruit juice and seed) were investigated against CCl4- induced cytotoxicity in HepG2 cells. Concentrations (1-10000 µg/ml) of the extracts were added to the cells, 1 h before the addition of 100 mM of CCl4. After 24 h, the cells were evaluated for toxicity, TBARs level and GSH content. The hydroalcoholic extracts of fruit juice and seeds with concentrations of 100 to 1000 µg/ml protected the cells against CCl4 induced cytotoxicity, but the ethyl acetate extract of fruit juice with higher concentration (1000 µg/ml) protected the cells against CCl4 cytotoxicity and the n-hexane extracts were less effective. The ethyl acetate and n-hexane extracts of seeds with different concentrations did not have any significant protective effect. The Punica granatum extracts themselves were not toxic towards cells with concentrations up to 1 mg/ml. Therefore, the results of the present study are somehow consistent with traditional beliefs about hepatoprotective effects of Punica granatum.
- انتشار مقاله: 26-10-1390
- نویسندگان: Hossein Niknahad,Akram Jamshidzadeh,Marjan Abbasian,Abbas Rezaeian Mehrabadi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Mitochondria,Cytochrome P-450 inhibition,Glyceryl trinitrate,GSH depletion,Isolated rat hepatocyte
- چکیده:
- چکیده انگلیسی: It has been proposed that organic nitrates such as glyceryl trinitrate (GTN), used in the treatment of cardiovascular diseases, act by producing nitric oxide (NO). However, the biochemical pathway for NO formation from GTN is not well understood. In the present study, we showed that nitrate formation from GTN, by isolated rat hepatocytes, was inhibited about 50% when cellular glutathione was depleted and about 40% when cytochrome P-450 was inactivated by SKF525A. This suggests that GTN is metabolized and/or NO is formed by three pathways in rat hepatocytes: 1) denitrification of GTN by GSH/GSH transferase system; 2) reduction of GTN by reduced cytochrome P-450; and 3) GTN can directly react with protein thiol groups of cellular macromolecules (transnitrosation). At much higher concentrations, GTN was toxic towards hepatocytes (LC 50= 2 mM for 2 h of incubation) and cytotoxicity was accompanied by GSH and ATP depletion. Depleting GSH and/or inactivating cytochrome P-450 beforehand markedly increased GTN cytotoxicity. The permeable thiol reductant dithioteritol unlike antioxidants was found to be an effective antidote, even if added to the cells an hour after GTN. The results suggest that GTN-induced cytotoxicity is mediated by transnitrosyllation of mitochondrial, structural and vital protein thiols.
- انتشار مقاله: 19-08-1390
- نویسندگان: Hossein Niknahad,Peter J. O Brien
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: oxidative stress,Cisplatin,Nephrotoxicity,Simvastatin
- چکیده:
- چکیده انگلیسی: Statins have antioxidant and anti-inflammatory effects that are not directly related to their cholesterol-lowering activity. This study aimed to investigate the effect of simvastatin on the extent of tissue damage in cisplatin-induced nephrotoxicity. Simvastatin was orally given to rats in different doses (1, 2 and 4 mg/kg), 1 h prior to cisplatin injection (5 mg/kg, i.p.). All animals were decapitated 5 days after cisplatin administration. Blood urea nitrogen, creatinine, K and Na levels were measured. The kidney samples used for the measurement of malondialdehyde and glutathione levels or were processed for histopathological studies. Simvastatin at 1 mg/kg caused a significant decrease in serum Na and a significant increase in serum K. Simvastatin at 2 mg/kg significantly increased serum Na, and at 4 mg/kg significantly prevented decrease of GSH levels by cisplatin and significantly decreased serum Na levels. The morphological changes induced by cisplatin treatment were prevented only by 4 mg/kg dose of simvastatin. Thus, simvastatin at 4 mg/kg dose is beneficial in cisplatin-induced nephrotoxicity in rats via prevention of lipid peroxidation, inflammation and endothelial function impairment.
- انتشار مقاله: 25-10-1389
- نویسندگان: Mohammad Javad Khoshnoud,Baligh Naji Abdeh Moghbel,Bita Geramizadeh,Hossein Niknahad
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Stability,Lyophilization,DOTAP nanoliposome,Survivin antisense,Transfection activity
- چکیده:
- چکیده انگلیسی: Survivin, an inhibitor of apoptosis protein is highly expressed in most cancers and considered as an attractive target for cancer antisense therapy. To vectorize antisense molecules, cationic nanoliposomes are generally used; however, their complexes are too instable, during shelf-life and upon exposure to blood components and extracellular matrix, to be used in-vivo. The present study aimed to develop fresh and lyophilized formulations of antisense/DOTAP nanoliposomes with different helper lipids and compare their shelf-life and biologic stabilities and their transfection activities in tumor cell lines. DOTAP nanoliposomes in combination with different helper lipids were prepared in HEPES buffer (20 mM, pH=7.4) by thin-layer hydration followed by thermobarrel extrusion and PTFE membrane filter sterilization. Nanoliposomes were characterized regarding their particle size distribution, final lipid recovery and physical stability. Following antisense loading by direct addition through electrostatic attraction, the degree of complexation was determined by ethidium bromide displacement assay. To stabilize the formulations, they were freeze-dried with 10% sucrose. The potential of the lyophilized and fresh formulations of FITC-labeled antisense to transfect different cell lines (SK-BR-3, MCF-7) was studied by flow cytometry. Fresh nanoliposomes of different formulations had a size in range of 50-100 nm. The degree of complex formation with antisense was determined almost 70-80% (N/P ~ 2) which decreased as incubated with either PBS or complete medium and heparin sulfate. Their average sizes significantly changed after preservation for few days at 4 °C. Lyophilization process compromised the particle size distribution and antisense loading efficiency of different formulations except for DOTAP/DOPE (1:1 mole ratio) which did not change significantly. Both fresh and lyophilized formulations exhibited the highest transfection activity at comparable levels especially in SK-BR-3 cells. As a conclusion, lyophilization process could promote stability and preserve transfection activity of the antisense complexes of DOTAP/DOPE (1:1) nanoliposomes.
- انتشار مقاله: 02-10-1389
- نویسندگان: Ali Mohammad Tamaddon,Hossein Niknahad,Mozhgan Nikravesh
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: oxidative stress,Doxorubicin,Captopril,Rat liver mitochondria
- چکیده:
- چکیده انگلیسی: Doxorubicin (DOX) is an anthracycline antibiotic that has been used for a long time in therapy of an array of human malignancies either alone or in combination with other cytotoxic agents. The dose-dependent cardiotoxicity of DOX significantly limits its anticancer efficacies. Oxidative stress caused by enhanced production of reactive oxygen species is an important contributor to DOX mitochondrial toxicity. In the present study, DOX produced a significant elevation in TBARS, which is an indicator of lipid peroxidation, and significantly inhibited the activity of superoxide dismutase in rat liver mitochondria. Mitochondrial GSH dramatically decreased while GSSG was increased upon treatment of mitochondria by DOX. Co-treatment with captopril significantly reduced the lipid peroxidation in mitochondria and prevented the inhibition of superoxide dismutase activity induced by DOX. Captopril also significantly increased the level of GSH in DOX-treated mitochondria. These results, therefore, suggest that captopril acts as an antioxidant and can protect the mitochondria against DOX-induced oxidative stress. This effect appears to be due to the sulfhydryl groups of captopril which may act as antioxidant or scavenger of reactive oxygen species.
- انتشار مقاله: 22-07-1388
- نویسندگان: Hossein Niknahad,Alireza Taghdiri,Afshin Mohammadi-Bardbori,Abbas Rezaeian Mehrabadi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی:
- چکیده:
- چکیده انگلیسی: Background: Cylophosphamide is used alone or in combination with other drugs for treatment of neoplastic diseases. Hemorrhagic cystitis is a major potential toxicity and dose limiting side effect of cyclophosphamide. The aim of this study was to evaluate the effects of lycopene compared with some antioxidants for the prevention of cyclophosphamide induced hemorrhagic cystitis in rats. Methods: In this study, male Sparague-Dawley rats divided into 17 groups of six animals. Group 1 received saline (10 ml/kg, i.p) as normal control, group 2 received cyclophosphamide (200 mg/kg, i.p) as a single dose, groups 3-10 received Mesna (40 mg/kg, i.p), N-acetylcysteine (100 mg/kg i.p), dithiotheritol (50 mg/kg, i.p), L-carnitine (200 and 400 mg/kg, i.p), grape seed extract (500 mg/kg i.p) and lycopene (0.1 and 0.5 mg/kg, i.p) alone. Groups 11-17 received Mesna (40 mg/kg, i.p), N-acetylcysteine (100 mg/kg, i.p), dithiotheritol (50 mg/kg, i.p), L-carnitine (400 mg/kg, i.p), grape seed extract (500 mg/kg, i.p) and lycopene (0.1 and 0.5 mg/kg, i.p), 5 minutes before, and 2 and 6 hours after administration of 200 mg/kg cyclophosphamide. Pathological and biochemical analysis was evaluated 24 hours after cyclophosphamide administration. Results: Mesna and N-acetylcysteine resulted in some but not full protection against cyclophosphamide toxicity compared to the controls. Lycopene (0.1 and 0.5 mg/kg) was efficient in protecting the bladder from cyclophosphamide induced hemorrhagic cystitis. However, dithiotheritol, L- carnitine and grape seed extract did not prevent hemorrhagic cystitis. Conclusion: Our results suggest that pre and co- treatment of lycopene (0.1 and 0.5 mg/kg) with cyclophosphamide may have therapeutic potential to inhibit the hemorrhagic cystitis by cyclophosphamide.
- انتشار مقاله: 22-02-1394
- نویسندگان: Akram Jamshidzadeh,Hossein Niknahad,Negar Azarpira,Afshin Mohammadi- Bardbori,Maryam Delnavaz
- مشاهده