Nonprotein Sulfhydryl Research Articles

English

Dyslipidaemia is characterised by enhanced production of reactive oxygen species and increased oxidative stress, which may affect liver, kidney and heart function. It is considered as a critical risk factor for cardiovascular and liver diseases. The aim of our study was to assess the effect of vanadium chloride on the oxidative stress state of liver, kidney and heart functions along with electrolyte balance during treatment of dyslipidemia using simvastatin in an animal model.  Rats were assigned to 1 of 5 groups: group 1, control group; group 2, received high fat diet (HFD); group 3, received HFD and 30 mg/kg body weight (BW) simvastatin; group 4, received HFD and 15 mg/kg BW vanadium chloride and group 5, received HFD, simvastatin and vanadium chloride. Drugs were administered orally by gavage for the last week of the experimental period. HFD was found to elicit a significant decrease (P ≤ 0.05) in non-protein sulfhydryls and significant increases (P ≤ 0.05) in hepatic and cardiac malondialdehyde (MDA), serum creatine kinase, lactate dehydrogenase, creatinine, urea, uric acid, calcium, sodium and potassium. Oral administration of vanadium chloride did not synergize simvastatin to ameliorate the negative effects of HFD, instead it worsens the negative effect of the HFD. Vanadium chloride administration decreased the concentration of non-protein sulfhydryls and increased MDA concentration in liver and heart tissues. It also caused further increase in the serum concentration of all measured serum parameters. These data proved that the vanadium concentration used in this study is not safe or efficient in ameliorating the oxidative stress or in improving kidney or heart functions in dyslipidemic rats. Key words: Vanadium, simvastatin, oxidative stress, kidney, rats. &nbsp

ОКИСНА МОДИФІКАЦІЯ БІЛКІВ У СИРОВАТЦІ КРОВІ ЩУРІВ В УМОВАХ КАРРАГІНАН-ІНДУКОВАНОГО ЗАПАЛЕННЯ ЗАДНЬОЇ КІНЦІВКИ ТА ТРИВАЛОГО ПРОФІЛАКТИЧНОГО ВВЕДЕННЯ ХОНДРОЇТИНУ СУЛЬФАТУ

The aim of the work was to investigate the preventive effect of Chondroitin Sulfate on the content of products of oxidative modification of proteins and the level of sulfhydryl groups in blood serum of rats at local inflammation of the hind limb. The studies were conducted on white non-linear, sexually mature male rats weighing 180–240 g, in compliance with the general ethical principles of experiments on animals. All animals were divided into four experimental groups. The first group – control: animals sub-planar injected 0,1 ml of 0,9 % NaCl solution into the posterior right limb. The second group – animals received a therapeutic dose of 3 mg x kg-1 chondroitin sulfate daily for 28 days daily. The third group – animals were infused intramuscularly with 0,1 ml of 0,9 % NaCl solution in the posterior right limb for 28 days and for 29 days inflammatory edema of the limb was stimulated (animals were sub-planar injected with 0,1 ml of 1 % carrageenan solution to the posterior right limb ) The fourth group – for 28 days rats were daily intramuscularly injected with a therapeutic dose of 3 mg x kg-1 chondroitin sulfate, after which on 29th day, inflammatory edema of the limb was stimulated. Animals were killed 3 hours after injection of carrageenan solution according to the protocol of the ethical committee, and then blood sampling for further research was quickly taken. The total number of animals involved in experimental studies was 40 individuals. The content of the products of oxidative modification of proteins (OMP) and oligopeptides was determined by the level of carbonyl derivatives that were detected in reaction with 2,4-dinitrophenylhydrazine. The level of total, protein-bound and non-protein sulfhydryl (SH) -groups was measured by the Elman method. It has been established that with carrageenan-induced inflammation of the posterior limb, the content of the products of oxidative modification of proteins increases and the content of sulfhydryl groups decreases in the serum. It was shown that the prophylactic administration of chondroitin sulfate based drug on animals with carrageenan-induced inflammation restored the abovementioned parameters.

Vaccinium macrocarpon Aiton Extract Ameliorates Inflammation and Hyperalgesia through Oxidative Stress Inhibition in Experimental Acute Pancreatitis.

We evaluated the effect of the hydroethanolic extract of fruits of Vaccinium macrocarpon (HEVm) in a model of acute pancreatitis (AP) in mice. AP was induced by two injections of L-arginine and animals were treated with HEVm (50, 100, and 200 mg/kg, p.o.) or vehicle (saline) every 24 h, starting 1 h after the induction of AP. Phytochemical analysis of the extract and measurement of inflammatory and oxidative stress parameters, as well as abdominal hyperalgesia, were performed. Catechin, epicatechin, rutin, and anthocyanins were identified in HEVm. Treatment with HEVm decreased L-arginine-induced abdominal hyperalgesia (from 48 to 72 h). Also, treatment with HEVm decreased L-arginine-induced pancreatic edema, pancreatic and pulmonary neutrophil infiltration, and levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6, after 72 h of induction. L-arginine-induced hyperamylasemia and hyperlipasemia were also reduced by the treatment with HEVm in comparison to vehicle-treated group. Moreover, lipoperoxidation, carbonyl radicals, nonprotein sulfhydryl groups, and activity of catalase and superoxide dismutase, but not glutathione peroxidase, were restored by the treatment with HEVm. These results show that treatment with HEVm decreased hyperalgesia and pancreatic/extrapancreatic inflammation and oxidative damage in L-arginine-induced AP, making this extract attractive for future approaches designed to treat this condition.

Anti-arthritic and gastroprotective activities of Ardisia crispa root partially mediated via its antioxidant effect.

Background Ardisia crispa Thunb A.DC (Myrsinaceae), commonly known as "hen's eyes", has been traditionally used in treating various inflammatory diseases. The present study evaluated anti-arthritic, gastroprotective and antioxidant activities of Ardisia crispa root hexane extract (ACRH) in various animal models. Methods Anti-arthritic activity was evaluated in complete Freund adjuvant (CFA)-induced adjuvant arthritis and gastroprotective effect was studied in the ethanol-induced ulcer model in rats. ACRH was further isolated to yield quinone-rich fraction (QRF) and both were analyzed for their total phenolic content, total flavonoid content and antioxidant activities in various antioxidant assays. Both ACRH and QRF were also analyzed for the quinone composition via gas chromatography analysis. Results ACRH exerted significant reduction of IL-1β and TNF-α at a lower dose range in CFA-induced arthritis, as well as exhibited its cytoprotective effect against ethanol-induced ulcer lesion via involvement of mucosal nonprotein sulfhydryl (NP-SH) groups. ACRH also showed higher phenolic and flavonoid contents, as well as better antioxidant activities than QRF. Conclusions These findings demonstrated the plant as a potential anti-inflammatory agent, with ACRH succeeded in inhibiting both arthritic and ulcerogenic effect, possibly mediated via its antioxidant effect.

5-Fluorouracil induces inflammation and oxidative stress in the major salivary glands affecting salivary flow and saliva composition

This study aimed to elucidate the effect of 5-fluorouracil (5-FU) on the histological aspects of the major salivary glands, salivary flow and saliva composition using an established oral mucositis model in hamsters. Oral mucositis was induced by two intraperitoneal administrations of 5-FU in two consecutive days (60 and 40mg/kg), followed by cheek pouch mucosa scratch, on day 4. The Pilocarpine-stimulated salivary flow was measured 4 and 10days after the first 5-FU injection. Salivary glands were harvested for histopathological analysis, measurement of inflammatory cells, quantification of pro-inflammatory cytokines (TNF-α and IL-1β), investigation of cell death and cell proliferation. Oxidative stress and oxidative defense system were also investigated in the salivary gland tissues using MDA (malondialdehyde), nitrite, non-protein sulfhydryl groups (NP-SH), SOD (superoxide dismutase) and CAT (catalase). In addition, the CAT and lysozyme activities and the IgA and SOD levels were evaluated in the saliva samples. 5-FU significantly reduced the pilocarpine-stimulated salivary flow rate on the 4th experimental day, associated with an increase in the SOD levels in saliva. Recovery of the salivary flow and SOD were observed on day 10, when an increase in the saliva lysozyme levels was detected. In addition, 5-FU promoted vacuolization in parotid (P) and periductal edema in submandibular (SM) gland, combined with an increase in the inflammatory cells influx, mostly observed on the 4th day in SM gland and on 4th and 10th days in P. Oxidative stress was found mostly on day 10 in SM, SL and P glands, associated with release of proinflammatory cytokines, observed in SM and SL glands, but not in P. 5-FU induces an inflammatory response in the major salivary glands, most observed ten days after its first injection, which may contribute to the major salivary glands hypofunction, leading to alterations in the salivary flow rate and composition.

Effects of ultrasound-assisted α-amylase degradation treatment with multiple modes on the extraction of rice protein

The effects of ultrasound-assisted α-amylase degradation (UAD) treatment with multiple modes on the extraction of rice protein (RP) from rice dreg powder were studied. The results showed that UAD treatment increased protein extraction rate significantly (p<0.05) compared to that of α-amylase degradation treatment and control. Among all the ultrasound mode treatments researched in this paper, sequential frequency ultrasound treatment presented higher protein extraction rate compared to that of simultaneous or single frequency ultrasound treatment. The highest protein extraction rate was obtained under 20/35kHz of sequential frequency UAD treatment with the protein extraction rate of 89.58% and protein purity of 92.99%. The test and analysis of fourier transform infrared spectroscopy, ultraviolet–visible spectroscopy, starch content, non-protein nitrogen content, SH and SS content, surface hydrophobicity, amino acids content and proteins characteristics were studied to reveal the mechanism of UAD on the protein extraction effect. After treated with UAD, the starch-protein agglomerates disintegrated completely, moreover, protein advanced structure was changed to some extent and the disulfide bond was partially broken, but the main chain structure (peptide chain), specificity of protein and amino acid composition were not obviously changed. Consequently, the structure modified RP extracted by UAD treatment presented higher solubility, emulsifying activity and foaming capacity, which was beneficial for the application of RP. In conclusion, UAD treatment is an effective method for maximizing extraction rate, purity and modifying properties of extracted protein.

Previous physical exercise alters the hepatic profile of oxidative-inflammatory status and limits the secondary brain damage induced by severe traumatic brain injury in rats.

An early inflammatory response and oxidative stress are implicated in the signal transduction that alters both hepatic redox status and mitochondrial function after traumatic brain injury (TBI). Peripheral oxidative/inflammatory responses contribute to neuronal dysfunction after TBI Exercise training alters the profile of oxidative-inflammatory status in liver and protects against acute hyperglycaemia and a cerebral inflammatory response after TBI. Approaches such as exercise training, which attenuates neuronal damage after TBI, may have therapeutic potential through modulation of responses by metabolic organs. The vulnerability of the body to oxidative/inflammatory in TBI is significantly enhanced in sedentary compared to physically active counterparts. Although systemic responses have been described after traumatic brain injury (TBI), little is known regarding potential interactions between brain and peripheral organs after neuronal injury. Accordingly, we aimed to investigate whether a peripheral oxidative/inflammatory response contributes to neuronal dysfunction after TBI, as well as the prophylactic role of exercise training. Animals were submitted to fluid percussion injury after 6weeks of swimming training. Previous exercise training increased mRNA expression of X receptor alpha and ATP-binding cassette transporter, and decreased inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α and interleukin (IL)-6 expression per se in liver. Interestingly, exercise training protected against hepatic inflammation (COX-2, iNOS, TNF-α and IL-6), oxidative stress (decreases in non-protein sulfhydryl and glutathione, as well as increases in 2',7'-dichlorofluorescein diacetate oxidation and protein carbonyl), which altered hepatic redox status (increases in myeloperoxidase and superoxide dismutase activity, as well as inhibition of catalase activity) mitochondrial function (decreases in methyl-tetrazolium and Δψ, as well as inhibition of citrate synthase activity) and ion gradient homeostasis (inhibition of Na+ ,K+ -ATPase activity inhibition) when analysed 24h after TBI. Previous exercise training also protected against dysglycaemia, impaired hepatic signalling (increase in phosphorylated c-Jun NH2-terminal kinase, phosphorylated decreases in insulin receptor substrate and phosphorylated AKT expression), high levels of circulating and neuronal cytokines, the opening of the blood-brain barrier, neutrophil infiltration and Na+ ,K+ -ATPase activity inhibition in the ipsilateral cortex after TBI. Moreover, the impairment of protein function, neurobehavioural (neuromotor dysfunction and spatial learning) disability and hippocampal cell damage in sedentary rats suggests that exercise training also modulates peripheral oxidative/inflammatory pathways in TBI, which corroborates the ever increasing evidence regarding health-related outcomes with respect to a physically active lifestyle.

Human CYP2A13 and CYP2F1 Mediate Naphthalene Toxicity in the Lung and Nasal Mucosa of CYP2A13/2F1-Humanized Mice.

Background:The potential carcinogenicity of naphthalene (NA), a ubiquitous environmental pollutant, in human respiratory tract is a subject of intense debate. Chief among the uncertainties in risk assessment for NA is whether human lung CYP2A13 and CYP2F1 can mediate NA’s respiratory tract toxicity.Objectives:We aimed to assess the in vivo function of CYP2A13 and CYP2F1 in NA bioactivation and NA-induced respiratory tract toxicity in mouse models.Methods:Rates of microsomal NA bioactivation and the effects of an anti-CYP2A antibody were determined for lung and nasal olfactory mucosa (OM) from Cyp2abfgs-null, CYP2A13-humanized, and CYP2A13/2F1-humanized mice. The extent of NA respiratory toxicity was compared among wild-type, Cyp2abfgs-null, and CYP2A13/2F1-humanized mice following inhalation exposure at an occupationally relevant dose (10 ppm for 4 hr).Results:In vitro studies indicated that the NA bioactivation activities in OM and lung of the CYP2A13/2F1-humanized mice were primarily contributed by, respectively, CYP2A13 and CYP2F1. CYP2A13/2F1-humanized mice showed greater sensitivity to NA than Cyp2abfgs-null mice, with greater depletion of nonprotein sulfhydryl and occurrence of cytotoxicity (observable by routine histology) in the OM, at 2 or 20 hr after termination of NA exposure, in humanized mice. Focal, rather than gross, lung toxicity was observed in Cyp2abfgs-null and CYP2A13/2F1-humanized mice; however, the extent of NA-induced lung injury (shown as volume fraction of damaged cells) was significantly greater in the terminal bronchioles of CYP2A13/2F1-humanized mice than in Cyp2abfgs-null mice.Conclusion:CYP2F1 is an active enzyme. Both CYP2A13 and CYP2F1 are active toward NA in the CYP2A13/2F1-humanized mice, where they play significant roles in NA-induced respiratory tract toxicity. https://doi.org/10.1289/EHP844

Dual effect of silymarin on experimental non-alcoholic steatohepatitis induced by irinotecan

Irinotecan-based regimens are commonly used for treatment of colorectal cancer, which is limited by mucositis and non-alcoholic steatohepatitis (NASH). Silymarin (SIL) prevents fatty liver disease in the clinical setting and in models of liver damage induced chemically. This study investigated the possible effect of SIL on irinotecan (IRI)-induced NASH. Swiss female mice were injected with saline (SAL 5ml/kg i.p.), IRI (50mg/kg i.p.), SIL (150mg/kg p.o.) or IRI (50mg/kg i.p.)+(SIL 1.5, 15 or 150mg/kg p.o.) thrice/week/7weeks. On the seventh week, blood samples were collected for transaminases assay and livers were collected for histopathology, measurement of the total lipids, malondyadehyde (MDA), non-protein sulfhydryl groups (NPSH), cytokines (IL-1β, IL 6 and IL-10), 3-nitrotyrosine (N-Tyr) and toll-like receptor 4 (TLR4) immunoexpression, quantification of NF-kB, α-smooth muscle actin (α-SMA), and Escherichia coli 16S rRNA gene (RRS) expression. IRI increased liver transaminases, neutrophil infiltration, lipid accumulation, MDA, IL-1β and IL-6 levels, N-Tyr and TLR4 immunostaining, NF-kB, α-SMA expression and RRS versus the SAL group (p<0.05). Additionally, SIL (1.5mg/kg) improved these parameters (p<0.05), except neutrophil infiltration and RSS versus the IRI group. Furthermore, the SIL (15mg/kg) only improved the inflammatory parameters, the expression of α-SMA and RRS versus the IRI group (p<0.05). The higher dose of SIL (150mg/kg) was even more deleterious than the intermediate dose. Therefore, silymarin showed a dual effect on liver damage induced by IRI. Hepatoprotection seems to involve the inhibition of oxidative stress and protein nitrosylation, preventing activation of hepatic fibrosis mechanisms.

Lutein attenuates diabetic-induced renal damage via inhibiting oxidative and nitrosative stresses

Diabetic nephropathy is a complex disease that involves production of free radicals, which are strong stimulus for pro-inflammatory factors. Present study was designed to explore the potential alleviating effects of lutein against streptozotocin-induced diabetic renal oxidation, inflammation and apoptosis in rats. Lutein was supplemented with diets content in three different doses (40, 80 and 160 mg/kg diets). Levels of glucose, albumin, creatinine and urea were determined in serum and urine. Renal expression of pro-inflammatory cytokines, nucleic acids and caspase-3 activity were estimated and also the kidney levels of thiobarbituric acid reactive substances (TBARS), total and non-protein sulfhydryl groups (T-SH and NP-SH), nitric oxide (NO) and inducible nitric oxide synthase (iNOS) along with superoxide dismutase (SOD) and catalase (CAT) activities. Renal histopathological features were analyzed. The diabetic animals showed apparent alterations in serum and urine biochemistry and also demonstrated evident elevated renal levels of pro-inflammatory mediators and apoptosis. Measured oxidative/nitrosative stress biomarkers were found altered markedly in the renal tissues of diabetic rats. Lutein supplementation to the diabetic animals significantly improved serum and urinary biochemistry. In renal tissue, the altered pro-inflammatory cytokines, nucleic acids and caspase-3 activity were ameliorated following lutein supplementation. Diabetic animals supplemented with lutein exhibited normal values of TBARS, T-SH, NP-SH and iNOS as well as SOD and CAT activities particularly in higher dose. Histological analysis further confirmed lutein’s renal protective effects. These results demonstrated clear evidence that lutein offered a significant protective effect against diabetes-induced nephrotoxicity by inhibiting the oxidative and nitrosative process in renal tissue.

Protective effect of N,N'-dimethylthiourea against stress-induced gastric mucosal lesions in rats.

In the present study, we examined the protective effect of N,N'-dimethylthiourea (DMTU), a scavenger of hydroxyl radical (·OH), against water-immersion restraint stress (WIRS)-induced gastric mucosal lesions in rats. When male Wistar rats fasted for 24 h were exposed to WIRS for 3 h, gastric mucosal lesions occurred with increases in the levels of gastric mucosal myeloperoxidase (MPO), an index of tissue neutrophil infiltration, pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin 1beta), lipid peroxide (LPO), and nitrite/nitrate (NOx), an index of nitric oxide synthesis, and decreases in the levels of gastric mucosal nonprotein SH and vitamin C and gastric adherent mucus. DMTU (1, 2.5, or 5 mmol/kg) administered orally at 0.5 h before the onset of WIRS reduced the severity of gastric mucosal lesions with attenuation of the changes in the levels of gastric mucosal MPO, pro-inflammatory cytokines, LPO, NOx, nonprotein SH, and vitamin C and gastric adherent mucus found at 3 h after the onset of WIRS in a dose-dependent manner. Serum levels of corticosterone and glucose, which are indices of stress responses, increased in rats exposed to WIRS for 3 h, but DMTU pre-administered at any dose had no effect on these increases. These results indicate that DMTU protects against WIRS-induced gastric mucosal lesions in rats by exerting its antioxidant action including ·OH scavenging and its anti-inflammatory action without affecting the stress response.

Aflatoxin B1 reduces non-enzymatic antioxidant defenses and increases protein kinase C activation in the cerebral cortex of young rats

Objectives: Aflatoxin B1 (AFB1) is the most widespread mycotoxin, and it is a feed contaminant and is highly toxic, causing carcinogenic, mutagenic, and teratogenic effects. Many researches clarified the peripheral effects of the exposition to AFB1; however, there are few studies explaining their effects on central nervous system. The aim of the present study was to evaluate the effects caused by acute oral administration of AFB1 on behavioral tests and selected biochemical parameters.Methods: Young male Wistar rats received a single administration of AFB1 (250 µg/kg/i.g.) and 48 hours thereafter they were subjected to behavioral analysis. After the tests, biochemical parameters were measured in the cerebral cortex.Results: Acute treatment with AFB1 caused neurotoxic effects, evidenced by a significant reduction in the levels of non-enzymatic antioxidant defenses, ascorbic acid, and non-protein sulfhydryl groups. In addition, AFB1 increased protein kinase C (PKC) activation, evidenced by an increase in phosphorylation of Ser957 of PKCα.Discussion: In this acute protocol, a single oral administration of AFB1 was able to cause changes in important neurochemical parameters, without concomitant, detectable behavioral alterations. These results reinforce that monitoring mycotoxin levels in food is essential to guarantee food security.

Momordica charantia polysaccharides ameliorate oxidative stress, hyperlipidemia, inflammation, and apoptosis during myocardial infarction by inhibiting the NF-κB signaling pathway

The polysaccharide extract of Momordica charantia has various biological activities; however, its effect on endothelial dysfunction in myocardial infarction remains unclear. To elucidate this, myocardial infarction was induced in rats using isoproterenol (ISP). Pretreatment with M. charantia polysaccharides (MCP; 150 or 300mg/kg) for 25days significantly inhibited increases in heart weight, the heart-weight-to-body-weight ratio, and infarction size, and ameliorated the increased serum levels of aspartate transaminase, creatine kinase, lactate dehydrogenase, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. In addition, MCP enhanced the activity of superoxide dismutase, catalase, and non-protein sulfhydryls, and decreased the level of lipid peroxidation. Moreover, MCP pretreatment downregulated the expression of proinflammatory cytokines (tumor necrosis factor alpha, interleukin (IL)-6, and IL-10), inflammatory markers (nitric oxide, myeloperoxidase, and inducible nitric oxide synthase), and apoptotic markers (caspase-3 and BAX), and upregulated Bcl-2 expression. Pretreatment with MCP reduced myonecrosis, edema, and inflammatory cell infiltration, and restored cardiomyocytes architecture. This myocardial protective effect could be related to the enhancement of the antioxidant defense system through the nuclear factor kappa B (NF-kB) pathways, and to anti-apoptosis through regulation of Bax, caspase-3, and Bcl-2.

Gastroprotective and anti-secretory mechanisms of 2-phenylquinoline, an alkaloid isolated from Galipea longiflora

We previously described the gastroprotective effect of 2-phenylquinoline (2-PQ), the main alkaloid isolated from the bark of Galipea longiflora (Rutaceae). However, despite the significant and promising results, the pharmacological mechanisms of the gastroprotection induced by 2-PQ have not been investigated. To evaluate the mechanisms underlying the gastroprotective effects of 2-PQ. We used an in vivo mouse ulcer model and in vitro methodologies involving H⁺/K⁺-ATPase and L929 murine fibroblasts. The gastroprotective activity of 2-PQ (10-100 mg/kg, orally, p.o) was assessed against gastric ulcer induced by 60% ethanol/0.03 M hydrochloric acid (HCl) in mice or that induced by indomethacin (80 mg/kg, p.o) in rats. The cytotoxicity was assessed in L929 murine fibroblasts. Ulcerated tissues were analyzed histologically, histochemically, and biochemically. The antisecretory activity of 2-PQ was evaluated in vivo and in vitro. 2-PQ showed no cytotoxicity, reduced the lesion area induced by ethanol/HCl (log half-maximal effective dose, ED50 = 1.507), and the histological evaluation supported these results. Furthermore, 2-PQ reduced indomethacin-induced gastric ulceration. The gastroprotection was accompanied by normalization of superoxide dismutase (SOD) and glutathione-S-transferase (GST) activity, an intense increase in reduced glutathione (GSH) levels, and reduction in lipid peroxide (LPO) and tumor necrosis factor (TNF)-α levels in the gastric mucosa. The antisecretory properties of 2-PQ were confirmed by the decreased volume and total acidity of the gastric juice, and it reduced histamine- or pentagastrin-stimulated gastric acid secretion. However, 2-PQ did not change the in vitro H⁺/K⁺-ATPase activity or the content of gastric-adhered mucous in mice. In addition, pretreatment with N-ethylmaleimide, NG-nitro-l-arginine methyl esters, yohimbine, or indomethacin reversed the gastroprotective effect of 2-PQ, suggesting nitric oxide, nonprotein sulfhydryl compounds, α-2-receptors, and prostaglandin were involved. 2-PQ provides gastroprotection by reducing oxidative damage and inhibiting acid secretion mediated by histaminergic and gastrinergic regulatory pathways.

N-Acetyl-L-Cysteine Protects Liver and Kidney Against Chromium(VI)-Induced Oxidative Stress in Mice.

Acute hexavalent chromium [Cr(VI)] compound exposure may lead to hepatotoxic and nephrotoxic effects. Cr(VI) reduction may generate reactive intermediates and radicals which might be associated with damage. We investigated effects of N-acetyl-l-cysteine (NAC) pre- or post-treatment on oxidative stress and accumulation of Cr in liver and kidney of Cr(VI)-exposed mice. Intraperitoneal potassium dichromate injection (20mgCr/kg) caused a significant elevation of lipid peroxidation in both tissues as compared to control (p<0.05). Significant decreases in non-protein sulfhydryl (NPSH) level, as well as enzyme activities of catalase (CAT) and superoxide dismutase (SOD) along with significant accumulation of Cr in the tissues (p<0.05) were of note. NAC pre-treatment (200mg/kg, ip) provided a noticeable alleviation of lipid peroxidation (p<0.05) in both tissues, whereas post-treatment exerted significant effect only in kidney. Similarly, Cr(VI)-induced NPSH decline was restored by NAC pre-treatment in both tissues (p<0.05); however, NAC post-treatment could only replenish NPSH in liver (p<0.05). Regarding enzyme activities, in liver tissue NAC pre-treatment provided significant restoration on Cr(VI)-induced CAT inhibition (p<0.05), while SOD enzyme activity was regulated to some extent. In kidney, SOD activity was efficiently restored by both treatments (p<0.05), whereas CAT enzyme alteration could not be totally relieved. Additionally, NAC pre-treatment in both tissues and post-treatment in liver exerted significant tissue Cr level decreases (p<0.05). Overall, especially NAC pre-treatment seems to provide beneficial effects in regulating pro-oxidant/antioxidant balance and Cr accumulation caused by Cr(VI) in liver and kidney. This finding may be due to several mechanisms including extracellular reduction or chelation of Cr(VI) by readily available NAC.

Phytochelatin synthesis in Dunaliella salina induced by arsenite and arsenate under various phosphate regimes

This study investigated the dynamic variations in thiol compounds, including cysteine (Cys), glutathione (GSH), and phytochelatins (PCs), in Dunaliella salina samples exposed to arsenite [As(III)] and arsenate [As(V)] under various phosphate (PO43−) regimes. Our results showed that GSH was the major non-protein sulfhydryl compound in D. salina cells. As(III) and As(V) induced PC syntheses in D. salina. PC2, PC3, and PC4 were all found in algal cells; the PC concentrations decreased gradually while exposed to As for 3 d. The synthesis of PC2–3 was significantly affected by As(III) and As(V) concentrations in the cultures. More PCs were detected in the As(V)-treated algal cells compared with the As(III) treatment. PC levels increased with As(III)/As(V) amount in the medium, but remained stable after 112μgL−1 As(V) exposure. In contrast, significant (p<0.001) positive correlations were observed between PC synthesis and intracellular As(III) content or As accumulation in As(III)-treated algal cells during the 72-h exposure. PO43− had a significant influence on the PC synthesis in algal cells, irrespective of the As-treated species. Reductions in As uptake and subsequent PC synthesis by D. salina were observed as the PO43− concentration in the growth medium increased. L-Buthionine sulfoximine (BSO) differentially influenced PC synthesis in As-treated D. salina under different extracellular PO43− regimes. Overall, our data demonstrated that the production of GSH and PCs was affected by PO43− and that these thiols played an important role in As detoxification by D. salina.

Protective effects of curcumin against mercury-induced hepatic injuries in rats, involvement of oxidative stress antagonism, and Nrf2-ARE pathway activation

Mercury (Hg) represents a ubiquitous environmental heavy metal that could lead to severe toxic effects in a variety of organs usually at a low level. The present study focused on the liver oxidative stress, one of the most important roles playing in Hg hepatotoxicity, by evaluation of different concentrations of mercuric chloride (HgCl2) administration. Moreover, the protective potential of curcumin against Hg hepatotoxic effects was also investigated. Eighty-four rats were randomly divided into six groups for a three-days experiment: control, dimethyl sulfoxide control, HgCl2 treatment (0.6, 1.2, and 2.4 mg kg-1 day-1), and curcumin pretreatment (100 mg kg-1 day-1) groups. Exposure of HgCl2 resulted in acute dose-dependent hepatotoxic effects. Administration of 2.4 mg kg-1 HgCl2 significantly elevated total Hg, nonprotein sulfhydryl, reactive oxygen species formation, malondialdehyde, apoptosis levels, serum lactate dehydrogenase, and alanine transaminase activities, with an impairment of superoxide dismutase and glutathione peroxidase in the liver. Moreover, HgCl2 treatment activated nuclear factor-E2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway in further investigation, with a significant upregulation of Nrf2, heme oxygenase-1, and γ-glutamylcysteine synthetase heavy subunit expression, relative to control. Pretreatment with curcumin obviously prevented HgCl2-induced liver oxidative stress, which may be due to its free radical scavenging or Nrf2-ARE pathway-inducing properties. Taking together these data suggest that curcumin counteracts HgCl2 hepatotoxicity through antagonizing liver oxidative stress.

Gastroprotective activity of synthetic coumarins: Role of endogenous prostaglandins, nitric oxide, non-protein sulfhydryls and vanilloid receptors

Natural or synthetic coumarins showed gastroprotective and antiulcer activity in animal models. In this study, we have synthetized twenty coumarins using classic methods to evaluate their gastroprotective effects on the ethanol/HCl-induced gastric lesion model in mice at 20mg/kg. Among the coumarins synthetized, compounds 6 and 10 showed the greatest gastroprotective activity being as active as lansoprazole at 20mg/kg and reducing gastric lesions by 75 and 76%, respectively. Then, in a second experiment, compounds 6 and 10 were re-evaluated in order to understand the possible mode of gastroprotective activity. Regarding coumarin 6, the protective effect was reduced by pre-treatment of the mice with N-ethylmaleimide and l-NAME suggesting that sulfhydryl compounds and endogenous nitric oxide are involved in its gastroprotective activity. While for coumarin 10 the effect was reduced by pre-treatment with indomethacin suggesting that prostaglandins are positively involved in its gastroprotective activity.

Treatment with Rhus tripartita extract curtails isoproterenol-elicited cardiotoxicity and oxidative stress in rats.

BackgroundConsumption of plant-derived nutraceuticals and crude drugs in traditional medicine is widely believed to confer beneficial effects in thwarting the progression of cardiovascular diseases. Rhus tripartita (family Anacardiaceae) has been traditionally used to treat a wide range of ailments.MethodsIn the present study we investigated the protective effects of an alcoholic extract of the stem part of Rhus tripartita male genotype (RTSM) on experimentally induced myocardial injury in rats. To this end, cardiac injury was induced by administration of isoproterenol (ISO) and serum enzyme markers, lipid profiles and cardiac tissue redox status were determined following RTSM treatment (250 and 500 mg/kg).ResultsAs a result, RTSM treatment significantly mitigated ISO-triggered upregulation of cardiac-specific markers of injury creatine kinase and lactate dehydrogenase. RTSM treatment significantly attenuated ISO-induced increase in serum cholesterol and triglycerides as well alterations in serum lipoproteins. Determination of oxidative balance showed that RTSM treatment significantly blunted ISO-induced increase in malondialdehyde and decrease in nonprotein sulfhydryl in cardiac tissue. Six compounds were isolated and identified as gallocatechin 1, taxifolin 2, myricetin-3-O-β-glucoside 3, catechin 4, epicatechin 5, and 3′,8-binaringenin 6. Compound 6 was isolated for the first time from the stem part of Rhus tripartita. Furthermore, RTSM treatment enhanced the survival fraction of cardiac cells exposed to oxidative stress in vitro.ConclusionWe conclude that the antioxidant properties of RTSM treatment underpin its cardioprotective pharmacological effects, thus, providing biological evidence for the treatment of cardiovascular diseases using Rhus tripartita in indigenous medicine.

Alteration in mitochondrial function and glutamate metabolism affected by 2-chloroethanol in primary cultured astrocytes

The aim of this study was to explore the mechanisms that contribute to 1,2-dichloroethane (1,2-DCE) induced brain edema by focusing on alteration of mitochondrial function and glutamate metabolism in primary cultured astrocytes induced by 2-chloroethanol (2-CE), a metabolite of 1,2-DCE in vivo. The cells were exposed to different levels of 2-CE in the media for 24h. Mitochondrial function was evaluated by its membrane potential and intracellular contents of ATP, lactic acid and reactive oxygen species (ROS). Glutamate metabolism was indicated by expression of glutamine synthase (GS), glutamate–aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) at both protein and gene levels. Compared to the control group, exposure to 2-CE could cause a dose dependent damage in astrocytes, indicated by decreased cell viability and morphological changes, and supported by decreased levels of nonprotein sulfhydryl (NPSH) and inhibited activities of Na+/K+-ATPase and Ca2+-ATPase in the cells. The present study also revealed both mitochondrial function and glutamate metabolism in astrocytes were significantly disturbed by 2-CE. Of which, mitochondrial function was much vulnerable to the effects of 2-CE. In conclusion, our findings suggested that mitochondrial dysfunction and glutamate metabolism disorder could contribute to 2-CE-induced cytotoxicity in astrocytes, which might be related to 1,2-DCE-induced brain edema.