首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 31 毫秒
1.
In the present study, we investigated the potential protective effects of royal jelly against azathioprine-induced toxicity in rat. Intraperitoneal administration of azathioprine (50 mg/kg B.W.) induced a significant decrease in RBCs count, Hb concentration, PCV%, WBCs count, differential count and platelet count, hepatic antioxidant enzymes (reduced glutathione and glutathione s-transferase) and increase of serum transaminases (alanine aminotransferase and aspartate aminotransferase enzymes) activities, alkaline phosphatase and malondialdehyde formation. Azathioprine induced hepatotoxicity was reflected by marked pathological changes in the liver. Oral administration of royal jelly (200 mg/kg B.W.) was efficient in counteracting azathioprine toxicity whereas it altered the anemic condition, leucopenia and thrombocytopenia induced by azathioprine. Furthermore, royal jelly exerted significant protection against liver damage induced by azathioprine through reduction of the elevated activities of serum hepatic enzymes. Moreover, royal jelly blocked azathioprine-induced lipid peroxidation through decreasing the malondialdehyde formation. In conclusion, royal jelly possesses a capability to attenuate azathioprine-induced toxicity.  相似文献   

2.
BackgroundExposure to chemotherapeutic agents such as acetaminophen may lead to serious liver injury. Calcium deregulation, angiotensin II production and xanthine oxidase activity are suggested to play mechanistic roles in such injury.ObjectiveThis study evaluates the possible protective effects of the calcium channel blocker amlodipine, the angiotensin converting enzyme inhibitor lisinopril, and the xanthine oxidase inhibitor allopurinol against experimental acetaminophen-induced hepatotoxicity, aiming to understand its underlying hepatotoxic mechanisms.Material and methodsAnimals were allocated into a normal control group, a acetaminophen hepatotoxicity control group (receiving a single oral dose of acetaminophen; 750 mg/kg/day), and four treatment groups receive N-acetylcysteine (300 mg/kg/day; a reference standard), amlodipine (10 mg/kg/day), lisinopril (20 mg/kg/day) and allopurinol (50 mg/kg/day) orally for 14 consecutive days prior to acetaminophen administration. Evaluation of hepatotoxicity was performed by the assessment of hepatocyte integrity markers (serum transaminases), oxidative stress markers (hepatic malondialdehyde, glutathione and catalase), and inflammatory markers (hepatic myeloperoxidase and nitrate/nitrite), in addition to a histopathological study.ResultsRats pre-treated with amlodipine, lisinopril or allopurinol showed significantly lower serum transaminases, significantly lower hepatic malondialdehyde, myeloperoxidase and nitrate/nitrite, as well as significantly higher hepatic glutathione and catalase levels, compared with acetaminophen control rats. Serum transaminases were normalized in the lisinopril treatment group, while hepatic myeloperoxidase was normalized in the all treatment groups. Histopathological evaluation strongly supported the results of biochemical estimations.ConclusionAmlodipine, lisinopril or allopurinol can protect against acetaminophen-induced hepatotoxicity, showing mechanistic roles of calcium channels, angiotensin converting enzyme and xanthine oxidase enzyme in the pathogenesis of hepatotoxicity induced by acetaminophen.  相似文献   

3.
BackgroundCisplatin (a platinum-compound) is a anti-neoplastic drug used in the treatment of various cancers but eventually results in severe adverse effects namely nephrotoxicity or renal disorder through generation of reactive oxygen species (ROS). This biochemical measurements and histopathology analysis investigated a possible protective effect of 1,2-diazole with regards to cisplatin-induced nephrotoxicity in experimental animals.MethodsAnimals were divided into four groups of six mice each. Group A: normal control, vehicle (1 % (w/v) gum acacia in phosphate buffer saline (PBS)). Group B: cisplatin group, vehicle + cisplatin (7.5 mg/kg). Group C: 1,2-diazole (10 mg/kg) + cisplatin and Group D: silymarin (50 mg/kg) + cisplatin. Each vehicle/drug treatment was given daily via intraperitoneal (ip) injection for 10 consecutive days starting from day 1. On group B, C and D cisplatin was given in single dose only on day 5 one hour post drug administration. Animals were allowed till 10th day and on day 11 all four groups animals were anesthetized. Blood samples were collected and serum was isolated for biochemical measurements. The rats were then euthanized by cervical dislocation and their kidney was recovered and then prepared for biochemical measurements and histopathology analyses.ResultsPretreatment with 1,2-diazole prevented nephrotoxicity induced by cisplatin through a protective mechanism that involved reduction of increased oxidative stress by significantly increasing the enzymatic and non enzymatic antioxidant enzymes such as glutathione peroxidase (GPx), glutathione (GSH) and diminishing the lipid peroxidation (LPO). The pretreatment with 1,2-diazole does not affect superoxide dismutase (SOD), catalase (CAT), serum urea and creatinine level during nephrotoxicity when compared to cisplatin-induced group. Moreover, the 1,2-diazole animals shown significant decrease in urine volume and kidney weight when compared with cisplatin-induced group. Histopathological findings reveals the protective efficacy of 1,2-diazole that restores histopathological changes against nephrotoxicity.ConclusionThese analysis will provide a critical evidence that 1,2-diazole could provide a new protective strategy against cisplatin-induced nephrotoxicity.  相似文献   

4.
Lead acetate (PbA) is one of the major environmental contaminants with grave toxicological consequences both in the developing and developed countries. The liver and erythrocyte antioxidant status and markers of oxidative were assessed. Exposure of rats to PbA led to significant decline (p < 0.05) in hepatic and erythrocyte glutathione peroxidase (GPx), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) content. Similarly, malondialdehyde (MDA) and H2O2 concentrations were significantly (p < 0.05) elevated. Histopathology and immunohistology of liver of rats exposed to PbA showed focal areas of necrosis and COX-2 expression after 6 weeks of PbA withdrawal. Taken together, hepatic and erythrocytes antioxidant defence system failed to recover after withdrawal of the exposed PbA for the period of the study. In conclusion, experimental animals exposed to PbA did not recover from hepatotoxicity and disruption of erythrocyte antioxidant defence system via free radical generation and oxidative stress.  相似文献   

5.
BackgroundAcetaminophen (APAP) is a conventional drug widely used in the clinic because of its antipyretic-analgesic effects. However, accidental or intentional APAP overdoses induce liver injury and even acute liver failure (ALF). Astaxanthin (ASX) is the strongest antioxidant in nature that shows preventive and therapeutic properties, such as ocular protection, anti-tumor, anti-diabetes, anti-inflammatory, and immunomodulatory effects. The aim of present study was to determine whether ASX pretreatment provides protection against APAP-induced liver failure.MethodsMale C57BL/6 mice were randomly divided into 7 groups, including control, oil, ASX (30 mg/kg or 60 mg/kg), APAP and APAP + ASX (30 mg/kg or 60 mg/kg) groups. Saline, olive oil and ASX were administered for 14 days. The APAP and APAP + ASX groups were given a peritoneal injection of 700 mg/kg or 300 mg/kg APAP to determine the 5-day survival rate and for further observation, respectively. Blood and liver samples were collected to detect alanine transaminase (ALT), aspartate transaminase (AST), inflammation, oxidative stress and antioxidant systems, and to observe histopathologic changes and key proteins in the mitogen-activated protein kinase (MAPK) family.ResultsASX pretreatment before APAP increased the 5-day survival rate in a dose-dependent manner and reduced the ALT, AST, hepatic necrosis, reactive oxygen species (ROS) generation, lipid peroxidation (LPO), oxidative stress and pro-inflammatory factors. ASX protected against APAP toxicity by inhibiting the depletion of glutathione (GSH) and superoxide dismutase (SOD). Administration of ASX did not change the expression of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and P38. However, phosphorylation of JNK, ERK and P38 was reduced, consistent with the level of tumor necrosis factor alpha (TNF-α) and TNF receptor-associated factor 2 (TRAF2).ConclusionASX provided protection for the liver against APAP hepatotoxicity by alleviating hepatocyte necrosis, blocking ROS generation, inhibiting oxidative stress, and reducing apoptosis by inhibiting the TNF-α-mediated JNK signal pathway and by phosphorylation of ERK and P38, which made sense in preventing and treating liver damage.  相似文献   

6.
ObjectiveWe evaluated the effect of astaxanthin (ASX) and vitamin E (vit E) on colistin methanesulfonate (CMS) induced-nephrotoxicity in rats.MethodsAnimals were treated with sterile saline, 300 000 or 450 000 IU/kg/day of CMS, CMS + ASX (20 mg/kg), CMS + vit E (100 mg/kg), or CMS + 1 ml/kg olive oil (OO) for 7 days. The plasma/urine creatinine (Cr) level, urine γ-glutamyl-transferase (GGT) level, and renal tissue activities in malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reductase (GSH), as well as renal histology were performed.ResultsCMS induced a tubular damage, increased the GGT and MDA levels, and decreased the activities of SOD, CAT, GPx and GSH. Co-treatment with ASX or vit E restored all biochemical parameters cited above and improved the histopathological damage.ConclusionNephrotoxicity induced by CMS might be due to oxidative damage. The improvement by ASX or vit E seems to be related to their antioxidant properties.  相似文献   

7.
BackgroundThe aim of the conducted studies was to evaluate the effect of 4-methylpyrazole, increasingly used in detoxifying treatments after ethylene glycol poisoning, on the activity of some antioxidant enzymes and lipid peroxidation formation in the liver of rats after experimental co-exposure to ethylene glycol and ethyl alcohol.MethodsThe trials were conducted on adult male Wistar rats. Ethylene glycol (EG) at the dose of 3.83 g/kg bw and ethyl alcohol (EA) at the dose of 1 g/kg bw were administered po, and 4-methylpyrazole (4-MP) at the dose of 0.01 g/kg bw was administered ip. Parameters of antioxidant balance were evaluated in hepatic cytosol, including the activity of the following enzymes: glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and lipid peroxidation level (TBARS).ResultsThe results suggest that evaluation of the effects of administrated 4-MP after co-exposure to EG and EA in the liver revealed statistically significant changes on antioxidant enzyme system and malondialdehyde formation.ConclusionThe changes in biomarkers activity indicate a greater production of free radicals which exceeds the capability of antioxidant system, appearing with oxidative stress in the group of animals treated by 4-MP combined with EG and EA.  相似文献   

8.
This study aims to determine the potential protective effects of ferulic acid against cisplatin-induced nephrotoxicity and to compare its effect with curcumin, a well-known protective agent against cisplatin- induced toxicity in rats. Administration of cisplatin resulted in high BUN (Blood Urea Nitrogen), creatinine, MDA (Malondialdehyde), MPO (Myeloperoxidase), TOS (Total Oxidative Status), PtNT (Protein Nitrotyrosine) levels (p < 0.05). Histological observations showed abnormal morphology of kidney; in addition with appearance of TUNEL positive cells indicating apoptosis in cisplatin administered group. HO-1 (Heme Oxygenase-1) levels measured by RT-PCR (Real Time Polymerase Chain Reaction), and TAS (Total Antioxidative Status) revealed antioxidant depletion due to cisplatin toxicity in animals (p < 0.05). All parameters showed improvement in groups treated with ferulic acid (p < 0.05). Ferulic acid treatment was found significant in preventing oxidative stress, increasing antioxidative status and regaining histological parameters to normal, indicating nephroprotective and antioxidant effects of this phenolic compound.  相似文献   

9.
The aim of the present study was to investigate the antioxidant and hepatotective effects of Schisandra chinensis pollen extract (SCPE) on CCl4-induced acute liver damage in mice. Total phenolic content, total flavonoid content, individual phenolic compounds and antioxidant activities (1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, chelating activity, and reducing power assay) were determined. In vivo study, SCPE (10, 20 and 40 g/kg) administered daily orally for 42 days prior to CCl4-intoxicated. Our results showed that SCPE had high total phenolic content (53.74 ± 1.21 mg GAE/g), total flavonoid content (38.29 ± 0.91 mg Rutin/g), quercetin and hesperetin may be the major contributor to strong antioxidant activities. Moreover, SCPE significantly prevented the increase in serum ALT and AST level in acute liver damage induced by CCl4, decreased the extent of malondialdehyde (MDA) formation in liver and elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver. The results indicated that SCPE has strong antioxidant activities and significant protective effect against acute hepatotoxicity induced by CCl4, and have been supported by the evaluation of liver histopathology in mice. The hepatoprotective effect may be related to its free radical scavenging effect, increasing antioxidant activity and inhibiting lipid peroxidation.  相似文献   

10.
The study objective was to investigate the potential of a beverage containing silymarin and l-arginine to alter basic physiological and urodynamic parameters in 22 normal healthy men aged 38–59 years. The volunteers drank 500 ml/day beverage without silymarin and l-arginine for 10 days followed, after a 7-day washout period, by the beverage with 400 mg silymarin and 295 mg l-arginine for 10 days. Blood and urine samples were collected on days 0, 10 and 27. The beverages were well-tolerated with no adverse effects. Most of the biochemical, hematological and urodynamic parameters remained unchanged. Total antioxidant capacity, total level of antioxidants, lipoperoxidation products (malondialdehyde), advanced oxidation products of proteins in plasma and glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase levels in erythrocytes were not influenced. Serum γ-glutamyl transferase, malondialdehyde level and activity of glutathione S-transferase in erythrocytes were lowered at day 27 and the concentration of total plasma SH-groups was higher on day 10. Using an ex vivo system, we found that silymarin/silybin at 10–100 μM is able to adsorb onto human erythrocytes and the complexes displayed antioxidant properties as studied using ex situ square-wave voltammetry. The trial showed that silymarin in vivo may protect erythrocytes against oxidative damage.  相似文献   

11.
Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage.  相似文献   

12.
Riboflavin has been shown to exhibit anti-inflammatory and antioxidant properties in the settings of experimental sepsis and ischaemia/reperfusion (I/R) injury. We investigated the effect of riboflavin on normothermic liver I/R injury. Mice were submitted to 60 min of ischaemia plus saline or riboflavin treatment (30 μmoles/kg BW) followed by 6 h of reperfusion. Hepatocellular injury was evaluated by aminotransferase levels, reduced glutathione (GSH) content and the histological damage score. Hepatic neutrophil accumulation was assessed using the naphthol method and by measuring myeloperoxidase activity. Hepatic oxidative/nitrosative stress was estimated by immunohistochemistry. Liver endothelial and inducible nitric oxide synthase (eNOS/iNOS) and nitric oxide (NO) amounts were assessed by immunoblotting and a chemiluminescence assay. Riboflavin significantly reduced serum and histological parameters of hepatocellular damage, neutrophil infiltration and oxidative/nitrosative stress. Furthermore, riboflavin infusion partially recovered hepatic GSH reserves and decreased the liver contents of eNOS/iNOS and NO. These data indicate that riboflavin exerts antioxidant and anti-inflammatory effects in the ischaemic liver, protecting hepatocytes against I/R injury. The mechanism of these effects appears to be related to the intrinsic antioxidant potential of riboflavin/dihydroriboflavin and to reduced hepatic expression of eNOS/iNOS and reduced NO levels, culminating in attenuation of oxidative/nitrosative stress and the acute inflammatory response.  相似文献   

13.
Cisplatin, a chosen drug for cancer treatment, is associated with severe nephrotoxicity, that limits its clinical use. Cisplatin involves enhanced oxidative stress, mitochondrial dysfunction and death of tubular cells. Nephroprotective role of PTY, prepared from methanolic extract of tubers of Pueraria tuberosa D.C., has been studied. PTY was orally given to rats in different doses for seven consecutive days, along with cisplatin (8 mg/kg B.W., i.p.) on 4th day. PTY significantly prevented the rise in serum creatinine, blood urea nitrogen. It prevented the decline in glutathione content, activities of superoxide dismutase and catalase and also prevented DNA damage, tubular swelling, cellular necrosis and protein cast deposition as compared to experimental control group in kidney. These changes were restored to near normal levels by PTY in dose of 40 mg/100 g B.W. Thus, it is proposed that the PTY possesses dose-dependent protective effect against cisplatin induced kidney damages, primarily through its free radical scavenging property.  相似文献   

14.
Two selenium withdrawal periods, 30 and 90 days, were considered for sturgeon fed 90 days three Se-cysteine diets (1.25, 5, 20 mg kg−1). Subsequently Acipenser baeri was fed the previous control diet (0.32 mg Se kg−1) for 90 days. Levels of superoxide dismutase, catalase, glutathione peroxidases, glutathione reductase, glyoxalase-II and malondialdehyde were determined in liver and kidney. Chemical analyses were carried out for the same tissues and for muscle. A reduction of Se levels in all tissues was recorded and the metalloid concentration decreased more quickly in liver than in kidney and muscle. At the end of the withdrawal Se concentration in muscle remained high in specimens previously fed 20 mg Se kg−1 diet, and disturbance of key antioxidant enzymes was recorded in liver and kidney. Moreover, alterations in glutathione peroxidases, and glyoxalase-II activities persisted even after 90 withdrawal days and were indicative of oxidative stress induced by Se-cysteine concentrations.  相似文献   

15.
BackgroundCisplatin is a platinum derivative frequently used in the chemotherapy of different solid tumors. This biochemical and histologic study investigated a possible protective effect of mirtazapine with regard to cisplatin-induced nephrotoxicity in the rat.MethodsThe animals were divided into 4 groups: 15 mg/kg mirtazapine + 10 mg/kg cisplatin, 30 mg/kg mirtazapine + 10 mg/kg cisplatin, only 10 mg/kg cisplatin and negative control (healthy) group. During 14 days, the treatment and treated control group took drugs, while the healthy animals were given distilled water on the same schedule. All animals were sacrificed by high-dose anesthesia at the end of the 14 days of treatment; their kidneys were removed and subjected to histologic and biochemical study.ResultsIn both of the doses we used, mirtazapine decreased the levels of malondialdehyde, creatinine, blood urea nitrogen and myeloperoxidase activity when compared to cisplatin group. On the other hand, it increased total glutathione level in all doses. Slight histopathological findings were determined in mirtazapine groups when compared to cisplatin control group.ConclusionIn the light of our results and literature knowledge, we can conclude that the protective effect of mirtazapine in cisplatin toxicity originates from its own antioxidant activity.  相似文献   

16.
Bi-n-butyl phthalate (BNBP) is an environmental pollutant. The aim of this study was to evaluate the protective effect of lipoic acid (LA) against testicular dysfunction associated with the intake of to BNBP- intoxicated rats. Adult male Wistar rats were divided into 4 groups of 6 animals each, and received medication orally for 14 days. Group I rats received 0.5 ml corn oil. Group II rats received LA (20 mg/kg B.W./day). Group III rats received BNBP (250 mg/kg B.W./day). Group IV rats received LA 24 h prior to BNBP intake. Testes weight, cauda sperm count and sperm motility were decreased significantly by 18.15%, 13.83% and 13.5%, respectively, after BNBP treatment. Significant increase by 12.1%, 10.20% and 11.51%, respectively, was observed in LA–BNBP rats. Significant increase by 1.53%, 1.5% and 1.8%, for serum follicle stimulating hormone, testosterone and total antioxidant status, respectively, were observed in LA–BNBP rats. Testicular lipid peroxides and lactate dehydrogenase enzyme were significantly decreased by 1.5 and 1.6 folds, respectively, in LA–BNBP rats were decreased after BNBP treatment. Testicular superoxide dismutase, catalase and glutathione reductase enzymes were significantly increased in LA–BNBP rats. LA–BNBP rats, decreased the damage to seminiferous tubules produced by BNBP intake. In conclusion, LA mitigated BNBP-induced testicular toxicity through antioxidant mechanism and by direct free radical scavenging activity.  相似文献   

17.
Indigofera caerulea Roxb. is a well known shrub among native medical practitioners in folk medicine used for the treatment of jaundice, epilepsy, night blindness and snake bites. It is also reported to have antioxidant and antimicrobial properties. However its actual efficacy and hepatoprotective mechanism in particular is uncertain. Thus the present study investigates the hepatoprotective effect of the methanolic extract of I. caerulea Roxb. leaves (MIL) and elucidation of its mode of action against carbon tetrachloride (CCl4) induced liver injury in rats. HPLC analysis of MIL when carried out showed peaks close to standard ferulic acid and quercetin. Intragastric administration of MIL up to 2000 mg/kg bw, didn't show any toxicity and mortality in acute toxicity studies. During “in-vivo” study, hepatic injury was established by intraperitoneal administration of CCl4 3 ml/kg bw (30% CCl4 in olive oil; v/v) twice a week for 4 weeks in Sprague–Dawley rats. Further, hepatoprotective activity of MIL assessed using two different doses (100 and 200 mg/kg bw) showed that intra-gastric administration of MIL (200 mg/kg bw) significantly attenuates liver injury. Investigation of the underlying mechanism revealed that MIL treatment was capable of reducing inflammation by an antioxidant defense mechanism that blocks the activation of NF-κB as well as inhibits the release of proinflammatory cytokine TNF-α and IL-1β. The results suggest that MIL has a significant hepatoprotective activity which might be due to the presence of phytochemicals namely analogues of ferulic acid and other phytochemicals which together may suppress the inflammatory signaling pathways and promote hepatoprotective activity against CCl4 intoxicated liver damage.  相似文献   

18.
Protective effect of mixture of flavonoids baicalin and chrysin (BCH) was studied against methylglyoxal (MG, a precursor of AGEs) induced cytotoxicity in NRK 52E kidney epithelial cells. Flow cytometry and microscopic analysis showed increased ROS generation, compromised antioxidant status, depolarization of mitochondria and apoptosis in MG stressed cells which were significantly transformed (p  0.01) during BCH co-treatment. In vivo studies in streptozotocin induced diabetic rats increased protein levels of iNOS, protein kinase C (PKC) and decreased IκB which was modulated by oral BCH treatment (75 mg baicalin and 10 mg chrysin/kg b.wt.). Increased levels of AGEs and their receptor proteins (RAGE) in diabetic rats were reduced significantly (p  0.01) in BCH treated group. Renal tubular injuries and deranged kidney function were significantly improved in BCH treated animals. The results indicate that the protection accorded by BCH through its antioxidant and anti-inflammatory effects can be explored for management of diabetic nephropathy.  相似文献   

19.
This study was undertaken to evaluate the protective effect of thymoquinone (TQ) against acetaminophen-induced hepatotoxicity. Mice were given TQ orally at three different doses (0.5, 1 and 2 mg/kg/day) for 5 days before a single hepatotoxic dose of acetaminophen (500 mg/kg i.p.). TQ supplementation dramatically reduced acetaminophen-induced hepatotoxicity, in a dose-dependent manner, as evidenced by decreased serum alanine aminotransferase (ALT) activities.Acetaminophen (500 mg/kg i.p.) resulted in a significant increase in serum ALT and total nitrate/nitrite, hepatic lipid peroxides and a significant decrease in hepatic reduced glutathione (GSH) and ATP in a time-dependent manner. Interestingly, supplementation of TQ (2 mg/kg/day) for 5 days before acetaminophen administration resulted in reversal of acetaminophen-induced increase in ALT, total nitrate/nitrite, lipid peroxide and a decrease in GSH and ATP. Moreover, TQ did not affect acetaminophen-induced early decrease in hepatic GSH indicating lack of the effect on the metabolic activation of acetaminophen.In conclusion, TQ is effective in protecting mice against acetaminophen-induced hepatotoxicity possibly via increased resistance to oxidative and nitrosative stress as well as its ability to improve the mitochondrial energy production.  相似文献   

20.
In this study, we investigated the protective effects of S-adenosyl-l-methionine (SAM), which is a precursor of cellular reduced glutathione (GSH), against the hepatotoxicity of pyrrolizidine alkaloid clivorine. MTT assay showed that SAM (5 μM) prevented the cytotoxicity of clivorine on human normal liver L-02 cells. DNA fragmentation assay showed that SAM (5 μM) improved clivorine-induced L-02 cell apoptosis, and the results of Western blot showed that SAM (5 μM) decreased clivorine-induced caspase-3 activation. Cellular GSH analysis showed that when L-02 cells were exposed to different concentrations (0, 3, 10, 30, 50 and 100 μM) of clivorine for 48 h, cellular GSH was decreased in a concentration-dependent manner, while SAM (5 μM) enhanced 50 μM clivorine decreased cellular GSH. Further MTT assay showed that 5 mM GSH and 5 mM N-acetyl-l-cysteine (NAC) both had protective effects against clivorine-induced hepatotoxicity. Our results suggest that SAM has protective effects against the hepatotoxicity of clivorine possibly by enhancing cellular GSH level and increasing cellular defensive ability against clivorine-induced cytotoxicity.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号