scholarly journals Effect of reduced glutathione on the indexes of oxidative stress and heme metabolism in liver and blood of rats under hemin chloride injection in vivo

Heme (iron-protoporphyrin IX) is involved in various cellular functions. The release of heme under hemolysis or under the damage of intracellular hemeproteins leads to its accumulation in tissues and, as a result, to the activation of free radical processes. Reduced glutathione (GSH) functions as an endogenous water-soluble antioxidant and a regulator of cells redox status, but its effect on the development of oxidative stress under hemin action in mammals remains not investigated. The aim of this work was to study the effect of hemin chloride on some hemeproteins activity and a number of prooxidant-antioxidant status indexes in rat liver and blood under GSH level modulation in vivo. White male rats weighing 170–280 g were taken for investigation. Hemin chloride and GSH were injected intraperitoneally. Blood plasma, homogenate, and postmitochondrial fraction of liver were the objects of study. Hemin chloride injection (50 mg/kg body weight) caused the increase in heme-containing products level in blood and free heme level in liver of rats, which was accompanied by the activation of free radical processes in these tissues. The accumulation of free heme in liver was proved by an increase in tryptophan 2,3-dioxygenase (TDO) holoenzyme activity and heme saturation. The pretreatment by GSH (500 mg/kg body weight) 0.5 h before hemin chloride injection normalized GSH content, but did not prevent heme accumulation, the decrease in triglycerides level and the increase in lipid hydroperoxides content in rat blood plasma under hemin action. In liver, GSH injection prevented the increase in lipid hydroperoxides and protein carbonyl derivatives concentration as well as in TDO holoenzyme activity, and decreased the degree of TDO heme saturation. All these changes occurred under GSH content increase in liver. Catalase activity in liver did not differ from the control values after hemin chloride injection as well as after glutathione and hemin coadministration. The analysis of relationship between parameters studied in this work revealed the strong positive correlation between GSH content in plasma and liver (r=0.85; p<0.001), which was consistent with literature data on the significant role of liver in supplying other tissues with reduced glutathione. A negative correlation was found between lipid peroxidation products and triglycerides content in plasma (r=–0.52; p<0.05), which indicated the participation of triglycerides unsaturated fatty acids as substrates in the peroxidation processes under hemin action. No significant correlation between GSH and hydroperoxides content, as well as between GSH and heme-containing products levels in blood plasma was revealed. Thus, the water-soluble antioxidant glutathione was not effective enough to prevent damage of lipid components in blood under hemin chloride action in the selected dose. In the liver, on the contrary, GSH injection prevented heme accumulation and oxidative stress development under hemin action, which was obviously associated with an increase in the GSH content in this organ.

2018 ◽  
Vol 8 (6-s) ◽  
pp. 48-52
Author(s):  
B. Sabari Senthil ◽  
V.K. Kalaichelvan ◽  
A. Kottai Muthu

Objective: The objective of the present study was to investigate the Evaluation of In vivo antioxidant activity of Ethanolic extract of root of Smilax zeylanica(EESZ) on Aluminium Chloride Induced apoptosis suppressing oxidative stress  in Wistar rats. Materials and Methods: The ethanolic extract from the roots of S. china by hot continuous percolation method. The rats were divided into 5 groups and each group consists of 6 animals. Rats were treated with EESC for 150 and 300 mg/ kg of body weight and piracetam, 0.5 mg/ kg of body weight for 14 successive days after inducing oxidative stress  with aluminium chloride (100 mg/ kg of body weight) for 60 days. The lipid peroxidation level (TBARS) and antioxidant activities like Superoxide dismutase (SOD), Catalase (CAT) and reduced Glutathione (GSH) were estimated in rats. Results: AlCl3 induced rats showed increased the TBARS and decreased the antioxidant enzymes like Superoxide dismutase (SOD), Catalase (CAT) and reduced Glutathione (GSH) when compared with the control group. The EESZ at higher dose 300 mg/ kg of body weight animals were significantly (P < 0.001) reduced the TBARS and increased the anti oxidant enzymes Superoxide dismutase (SOD), Catalase (CAT) and reduced Glutathione (GSH) when compared with the AlCl3 treated group Conclusion: Findings of the present study revealed that Ethanolic extract from roots of Smilax zeylanica  may be used as a significant source of natural antioxidant, which might be helpful in preventing the progress of various oxidative stresses.                    Keywords: S. zeylanica, antioxidant, ethanolic extract, TBARS, rats.


2020 ◽  
Vol 84 (2) ◽  
Author(s):  
Wafa Trabelsi ◽  
Chaima Fouzai ◽  
Imene Chetoui ◽  
Safa Bejaoui ◽  
Khaoula Telahigue ◽  
...  

Acrylamide (ACR) is among the most deleterious pollutants in the environment and presents a serious risk to humans and ecosystems. The purpose of this study was to assess its effects when administered at different concentrations (5, 10 and 20 mg L–1) to evaluate antioxidant status in the gills of Mactra stultorum. Our results showed, after five days of treat­ment, an increase in malondialdehyde (MDA), lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), reduced glutathione (GSH), ascorbic acid (Vit C) and metallothionein (MDA) levels in gills of treated clams compared with controls. Moreover, an increase in superoxide dismutase (SOD) and a significant decrease in glutathione peroxidase (GPx) activities were also observed. Acrylamide induced neurotoxicity, as evidenced by the inhibition of acetylcholinesterase (AChE) activity in a dose-dependent manner. Overall, our results indicated that oxidative stress may be considered one of the mechanisms behind acrylamide toxicity in bivalves, although the subject requires more research.


2007 ◽  
Vol 52 (2) ◽  
pp. 705-715 ◽  
Author(s):  
Sanjay Kumar ◽  
Sajal Kumar Das ◽  
Sumanta Dey ◽  
Pallab Maity ◽  
Mithu Guha ◽  
...  

ABSTRACT A series of [(aryl)arylsufanylmethyl]pyridines (AASMP) have been synthesized. These compounds inhibited hemozoin formation, formed complexes (KD = 12 to 20 μM) with free heme (ferriprotoporphyrin IX) at a pH close to the pH of the parasite food vacuole, and exhibited antimalarial activity in vitro. The inhibition of hemozoin formation may develop oxidative stress in Plasmodium falciparum due to the accumulation of free heme. Interestingly, AASMP developed oxidative stress in the parasite, as evident from the decreased level of glutathione and increased formation of lipid peroxide, H2O2, and hydroxyl radical (·OH) in P. falciparum. AASMP also caused mitochondrial dysfunction by decreasing mitochondrial potential (ΔΨm) in malaria parasite, as measured by both flow cytometry and fluorescence microscopy. Furthermore, the generation of ·OH may be mainly responsible for the antimalarial effect of AASMP since ·OH scavengers such as mannitol, as well as spin trap α-phenyl-n-tertbutylnitrone, significantly protected P. falciparum from AASMP-mediated growth inhibition. Cytotoxicity testing of the active compounds showed selective activity against malaria parasite with selectivity indices greater than 100. AASMP also exhibited profound antimalarial activity in vivo against chloroquine resistant P. yoelii. Thus, AASMP represents a novel class of antimalarial.


2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Monika A. Olszewska ◽  
Joanna Kolodziejczyk-Czepas ◽  
Magdalena Rutkowska ◽  
Anna Magiera ◽  
Piotr Michel ◽  
...  

Polyphenol-rich plant extracts might alleviate the negative impact of oxidative stress and inflammation, but careful phytochemical standardisation and evaluation of various mechanisms are required to fully understand their effects. In this context, flower extracts of Sorbus aucuparia L.—a traditional medicinal plant—were investigated in the present work. The LC-MS/MS profiling of the extracts, obtained by fractionated extraction, led to the identification of 66 constituents, mostly flavonols (quercetin and sexangularetin glycosides with dominating isoquercitrin), pseudodepsides of quinic and shikimic acids (prevailing isomers of chlorogenic acid and cynarin), and flavanols (catechins and proanthocyanidins). Minor extract components of possible chemotaxonomic value were flavalignans (cinchonain I isomers) and phenylamides (spermidine derivatives). As assessed by HPLC-PDA and UV-spectrophotometric studies, the extracts were polyphenol-abundant, with the contents up to 597.6 mg/g dry weight (dw), 333.9 mg/g dw, 382.0 mg/g dw, and 169.0 mg/g dw of total phenolics, flavonoids, proanthocyanidins, and caffeoylquinic acids, respectively. Their biological in vitro effects were phenolic-dependent and the strongest for diethyl ether, ethyl acetate, and n-butanol fractions of the methanol-water (7 : 3, v/v) extract. The extracts showed significant, concentration-dependent ability to scavenge in vivo-relevant radical/oxidant agents (O2∙−, OH∙, H2O2, ONOO–, NO∙, and HClO) with the strongest effects towards OH∙, ONOO–, HClO, and O2∙− (compared to ascorbic acid). Moreover, the extracts efficiently inhibited lipoxygenase and hyaluronidase (compared to indomethacin) but were inactive towards xanthine oxidase. At in vivo-relevant levels (1-5 μg/mL), they also effectively protected human plasma components (proteins and lipids) against ONOO–-induced oxidative damage (reduced the levels of 3-nitrotyrosine, lipid hydroperoxides, and thiobarbituric acid-reactive substances) and normalised/enhanced the total nonenzymatic antioxidant capacity of plasma. In cytotoxicity tests, the extracts did not affect the viability of human PBMCs and might be regarded as safe. The results support the application of the extracts in the treatment of oxidative stress-related pathologies cross-linked with inflammatory changes.


2006 ◽  
Vol 3 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Yuta Inokuchi ◽  
Masamitsu Shimazawa ◽  
Yoshimi Nakajima ◽  
Shinsuke Suemori ◽  
Satoshi Mishima ◽  
...  

Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory) effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retinain vitroand/orin vivo.In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2) exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin–reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus) by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation), as also did trolox (water-soluble vitamin E). In micein vivo, propolis (100 mg kg−1; intraperitoneally administered four times) reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer) induced by intravitrealin vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage bothin vitroandin vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects.


2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Victor Paromov ◽  
Sudha Kumari ◽  
Marianne Brannon ◽  
Naga S. Kanaparthy ◽  
Hongsong Yang ◽  
...  

Sulfur mustard or mustard gas (HD) and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES), or “half-mustard gas,” are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated usingin vitromodel systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes) increased cell viability and attenuated production of reactive oxygen species (ROS) in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM) increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously describedin vivoprotective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.


2018 ◽  
Vol 64 (3) ◽  
pp. 261-267
Author(s):  
E.I. Gorina ◽  
T.N. Popova ◽  
K.K. Shulgin ◽  
S.S. Popov ◽  
L.F. Panchenko ◽  
...  

The effect of the synthetic biguanide derivatives N-[imino(1-piperidinyl)methyl]guanidine (NIPMG) and 1,3-dimethyl-5-[(carbamimidamidomethanimidoil) amino]benzoyl-1,3dicarboxylate (DCB) on the degree of proteins oxidative modification (POM) and the DNA fragmentation, the content of the lipid peroxidation primary products – conjugated dienes (CD), and the activity of glutathione antioxidant system in the liver and heart of rats with experimental hyperglycemia was investigated. Administration of the biguanides (15.0 mg/kg) to hypoglycemic rats promoted reduction of the free radical processes intensity in the studied tissues. Data about CD and POM level changes in hyperglycemic rats treated by NIPMG and DKB correlate with the results of DNA fragmentation degree evaluation. At the same time, the activity of antioxidant enzymes (glutathione peroxidase and glutathione reductase), and the reduced glutathione content in the liver and heart of rats changed toward control values. For metformin, which was used as a comparison drug, changes in the studied parameters in the same direction were also found. These results indicate the ability of the tested biguanide derivatives to exhibit a positive regulatory effect on free radical homeostasis, reducing the degree of oxidative stress at this pathology.


2018 ◽  
Vol 9 (2) ◽  
pp. 300-307
Author(s):  
Y. M. Stepanov ◽  
L. A. Ponomarenko ◽  
O. A. Lykholat ◽  
T. M. Shevchenko ◽  
O. M. Khomenko ◽  
...  

The processes of effect of L-arginine-L-glutamate on peroxidation and slime-forming function of the stomach cells, the system of antioxidant defense in the blood, liver and brain tissues of rats with experimental pathology of the gastroduodenal zone have been investigated. The animals were divided into four groups. Group I – control group were rats injected intragastrically through a probe physiological solution. Group II included animals with erosive ulcerative lesions of the gastroduodenal zone. Modeling of the erosive ulcerative lesions was carried out by intragastric administration of medical bile (1 ml/100 g) in combination with immobilization-cold stress for 1 hour at + 4 ºС for a period of seven days. Rats of group ІІІ simultaneously received an intra-abdominal 4% solution of L-arginine-L-glutamate in a dose of 20 mg per 100 g of body weight at the same time as the erosive ulcerative lesions modeling. To clarify the role of NO-ergic mechanism of L-arginine-L-glutamate influence on the quantitative composition of mucins and free radical processes rats in group ІV with erosive ulcerative lesions were injected with non-selective NO-synthase inhibitor, L-NAME (L-NG-nitroarginine methyl ester), at a dose of 1 mg per 100 g at the same time as injections of 4% solution of L-arginine-L-glutamate. The simulation of erosive-ulcerative lesions of the gastroduodenal zone in the experimental animals was accompanied by the intensification of lipid peroxidation processes, the imbalance of the antioxidant defense systems and the development of oxidative stress in the blood, tissues of the stomach, liver and brain, which has tissue-specific features. In the blood of the animals, the activation of the enzymatic link of antioxidant defense did not compensate for free radical processes, as a result, the exhaustion of the reduced glutathione pool occurred, and the level of TBA-active products increased both in plasma and in erythrocytes. There was a depression of the enzymes of the antioxidant defense and a decrease in the level of recovered glutathione, indicating decompensating of the liver antioxidant protection systems in the liver tissue of the rats. In the experimental animals , formation of erosive ulcerative lesions was accompanied by destabilization of the oxidation-reducing processes in the brain, which led to the intensification of the lipoperoxidation. In the mucous membrane of the stomach of the experimental animals, the total number of protection factors – secretory mucins with a simultaneous structural change – decreased. The use of L-arginine-L-glutamate reduced the manifestations of oxidative stress in the stomach tissue of animals with experimental pathology and normalized the quantitative and qualitative composition of mucins. In the blood, liver tissues and brain of the rats, L-arginine-L-glutamate injections activated the enzymes of the first anti-radical linkage – superoxide dismutase and catalase contributed to the increase of the pool of reduced glutathione and the deceleration of free radical reactions. Investigation of reactions to the action of the inhibitor provides the basis for the hypothesis of the NO-mediated action of L-arginine-L-glutamate on the formation of S-nitrosothiols, as evidenced by the high level of reduced glutathione when the inhibitor is used.


Author(s):  
ZAFAR JAVED KHAN ◽  
NAEEM AHMAD KHAN

Objective: The aim of the present study was to investigate the in vivo antioxidant potential of 50% ethanolic extract of Sesamum indicum against high-fat diet-induced rats. Methods: Animals were treated with plant extract for 30 d, and a high-fat diet was given to all groups except plain control, throughout, out the study. And alpha-tocopherol acetate (Vit, E) was used as standard. Pre-treatment with 16 mg/100 gm of body weight of 50% ethanolic extract of Sesamum indicum improved the Superoxide dismutase, catalase, glutathione, and lipid peroxidation levels significantly as compared to control group. Results: The present studies revealed that Sesamum indicum has significant in vivo antioxidant activity and can be used to protect tissue from oxidative stress. The result showed that the activities of SOD, catalase, lipid peroxidase, and glutathione, in the group treated with high-fat diet declined significantly than that of normal group. Conclusion: 50% ethanolic extract of in the dose of Sesamum indicum 16 mg/100 gm of body weight, has improved the SOD, catalase, glutathione, and lipid peroxidase levels significantly, which were comparable with high-fat-diet-induced rats. Based on this study we conclude that the 50% ethanolic extract of Sesamum indicum possesses in vivo antioxidant activity and can be employed in protecting tissue from oxidative stress.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Prabhakar Singh ◽  
Syed Ibrahim Rizvi

Curcumin ((1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), the yellow biphenolic pigment isolated from turmeric (Curcuma longa), has various medicinal benefits through antioxidation, anti-inflammation, cardiovascular protection, immunomodulation, enhancing of the apoptotic process, and antiangiogenic property. We explored the effects of curcuminin vitro(10−5 M to 10−8 M) andin vivo(340 and 170 mg/kg b.w., oral) on Na+/K+ATPase (NKA), Na+/H+exchanger (NHE) activity, and membrane lipid hydroperoxides (ROOH) in control and experimental oxidative stress erythrocytes of Wistar rats. As a result, we found that curcumin potently modulated the membrane transporters activity with protecting membrane lipids against hydro-peroxidation in control as well as oxidatively challenged erythrocytes evidenced by stimulation of NKA, downregulation of NHE, and reduction of ROOH in the membrane. The observed results corroborate membrane transporters activity with susceptibility of erythrocyte membrane towards oxidative damage. Results explain the protective mechanism of curcumin against oxidative stress mediated impairment in ions-transporters activity and health beneficial effects.


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