Nonprotein Sulfhydryl Research Articles

Protective Effect of Oligonol on Dimethylnitrosamine-Induced Liver Fibrosis in Rats via the JNK/NF-κB and PI3K/Akt/Nrf2 Signaling Pathways.

Oligonol is a low molecular weight polyphenol product derived from lychee fruit by a manufacturing process. We investigated oligonol’s anti-fibrotic effect and the underlying mechanism in dimethylnitrosamine (DMN)-induced chronic liver damage in male Sprague–Dawley rats. Oral administration of oligonol (10 and 20 mg/kg body weight) ameliorated the DMN-induced abnormalities in liver histology and serum parameters in rats. Oligonol prevented the DMN-induced elevations of TNF-α, IL-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase expressions at the mRNA level. NF-κB activation and JNK phosphorylation in DMN-treated rats were ablated by oligonol. Oligonol reduced the enhanced production of hepatic malondialdehyde and reactive oxygen species and recovered protein SH, non-protein SH levels, and catalase activity in the DMN treated liver. Nrf2 translocation into the nucleus was enhanced, and PI3K and phosphorylated Akt levels were increased by administering oligonol. The level of hepatic fibrosis-related factors such as α-smooth muscle actin, transforming growth factor-β1, and type I collagen was reduced in rats treated with oligonol. Histology and immunohistochemistry analysis showed that the accumulation of collagen and activation of hepatic stellate cells (HSCs) in liver tissue were restored by oligonol treatment. Taken together, oligonol showed antioxidative, hepatoprotective, and anti-fibrotic effects via JNK/NF-κB and PI3K/Akt/Nrf2 signaling pathways in DMN-intoxicated rats. These results suggest that antioxidant oligonol is a potentially useful agent for the protection against chronic liver injury.

Daphnetin Ameliorates Corticosterone-Induced Depressive-Like Behavior and Oxidative Stress in Mice Via Nuclear Factor Erythroid 2-Related Factor/Heme Oxygenase-1 Pathway

We have investigated the effect of daphnetin on depressive-like behavior and oxidative stress caused by corticosterone in mice. To this end, we have analyzed the effect of corticosterone alone and combination of corticosterone and daphnetin on three behavioral indices of depressive-like behavior - sucrose consumption rate, forced swimming test, and tail suspension test as well as biochemical markers of oxidative stress - malondialdehyde, nitrite, protein carbonyl, nonprotein sulfhydryl and glutathione contents as well as hippocampal cell apoptosis. The results support the conclusion that daphnetin diminished corticosterone induced depressive like behavior and oxidative stress by activating Nrf2/HO-1 pathway.

Low Molecular Weight Organic Acids Increase Cd Accumulation in Sunflowers through Increasing Cd Bioavailability and Reducing Cd Toxicity to Plants

The use of low molecular weight organic acids (LMWOAs) for the phytoremediation of heavy metals has become a promising technique. We chose five kinds of organic acids (oxalic acid (OA), acetic acid (AA), tartaric acid (TA), malic acid (MA), and citric acid (CA)) with six application rates (1, 2, 3, 4, 5, and 6 mmol/kg) and planted sunflowers (Helianthus annuus L.) in Cd-polluted soil to study the efficiency of the phytoremediation of Cd and the degree of Cd toxicity to plants. Treatment with no acid application served as the control (CK). We analyzed the plant height dry matter and the Cd and nonprotein sulfhydryl (NPT) contents in the soil and plant tissues. OA, AA, TA, MA, and CA increased plant heights by 17.6–47.40%, 21.25–39.17%, 12.5–35.52, 5.10–30.50%, and 16.15–49.17%, respectively; shoot biomass of the sunflowers was increased except with MA. NPT decreased under LMWOA application, which, in the roots, increased with the increase in root Cd under LMWOA treatment; however, there was no obvious relationship in the stems and leaves. The composition of Cd in the soil changed significantly under the LMWOA treatments compared to the CK, and the changes in carbonate Cd and Fe-Mn oxide Cd were the most prominent. The plant Cd accumulation of OA, AA, TA, MA, and CA increased by 43.31%, 55.25%, 48.69%, 0.52%, and 32.94%, respectively, and the increase in root Cd content and shoot dry matter quality promoted the increase in Cd accumulation. The LMWOAs were more likely to affect the phytoremediation of Cd by changing total P (TP) rather than total N (TN).

Nephroprotective effect of persimmon leaves (Diospyros kaki L.f.) against CCl4-induced renal toxicity in Swiss Albino rats

Diospyros kaki L.f. fruit and leaves are traditionally used for the treatment of hypertension, angina, internal hemorrhage, antithrombotic and anti-inflammatory effects.In the current study, the protective effects of ethyl acetate (Per-1), n-butanol (Per-2), and aqueous (Per-3) fractions of Diospyros kaki leaves against carbon tetrachloride (CCl4) induced nephrotoxicity in Swiss albino rats were tested. Animal were divided into nine groups; each group consists of six animals. The groups were : group I was untreated and kept as control, group II was treated with CCl4 only, group III (silymarin with CCl4); group IV (Per-1 100 mg/kg with CCl4);group V (Per-1 200 mg/kg with CCl4); group VI (Per-2 100 mg/kg with CCl4); group VII (Per-2 200 mg/kg with CCl4); group VIII (Per-3 100 mg/kg with CCl4); and group IX (Per-3 200 mg/kg with CCl4). Silymarin was used as standard drug. All tested fractions were found active (except Per-1 at low dose of 100 mg/kg) with significant value (p < 0.001) compared to CCl4 only group. Serum creatinine, malondialdehyde (MDA), and uric acid were significantly (p < 0.001) lowered in group VII–IX as compared to CCl4 only group. Similarly, total protein (TP) and non-protein sulfhydryls(NP-SH) level in kidney tissues were significantly (p < 0.001) elevated in the same groups compared to CCl4 only group. Further to check the cardio-protective potential, biochemical parameters such as LDH, creatine kinase, TP, MDA, and NP-SH levels in myocardial tissues were also estimated.These findings confirmed that the n-butanol and aqueous fractions are active and recommended for further bioactive phytoconstituents screening. Repeated column chromatography on silica gel G and sephadex-LH-20 of the active n-butanol fraction, four flavonoids were isolated. Based on the spectroscopic NMR data, compounds were identified as kaempferol (1), quercetin (2), astragalin (3), and rutin (4).

Opioid System Contributes to the Trifluoromethyl-Substituted Diselenide Effectiveness in a Lifestyle-Induced Depression Mouse Model.

Energy-dense foods and ethanol consumption are associated with mood disorders. m-Trifluoromethyl-diphenyl diselenide [(m-CF3-PhSe)2] has been a prominent pharmacological target due to its antidepressant-like effects. This study investigated if the modulation of opioid and glucocorticoid receptors and its well-known antioxidant property contribute to the (m-CF3-PhSe)2 antidepressant-like effect in young mice subjected to an energy-dense diet and ethanol intake. Swiss male mice [postnatal day (PND) 25] were exposed to an energy-dense diet (containing 20% fat and 20% carbohydrate) or standard chow until the PND 67. Mice received ethanol (2g/kg) or water administration (3 times a week, intragastrically [i.g.]) from PND 45 to PND 60. After that, mice received (m-CF3-PhSe)2 (5mg/kg/day; i.g) or vegetal oil administration from PND 60 to 66. Mice performed the behavioral tests to evaluate the depressive-like phenotype. The results showed that individually neither an energy-dense diet nor ethanol group induced a depressive-like phenotype, but the association of both induced this phenotype in young mice. Oxidative stress was characterized by the increase of malondialdehyde, the decrease in the superoxide dismutase activity, and non-protein sulfhydryl levels in the cerebral cortex of depressive-like mice. Depressive-like mice showed an increase in the protein levels of opioid receptors and depletion in those of glucocorticoid. (m-CF3-PhSe)2 abolished depressive-like phenotype and oxidative stress as well as modulated the levels of glucocorticoid and opioid receptors. In conclusion, the modulation of opioid and glucocorticoid receptors and the antioxidant property contributed to the (m-CF3-PhSe)2 antidepressant-like effect in young mice exposed to an energy-dense diet and ethanol intake.

Dietary ethanol extract of mango increases antioxidant activity of pork

Ethanol extract of mango seeds (EEMS) are composed of several polyphenolic compounds with considerable in vitro antioxidant activity that can be used in pig feed and may contribute positively to meat quality characteristics. The aim of this study was to evaluate the effect of EEMS as a source of antioxidants in growing-finishing pig diets on meat quality, lipid stability, sulfhydryl groups non-proteinaceous (SG-NP), total phenolic compounds, total antioxidant potential and total antioxidant activity of meat after 1 and 7 days of refrigeration storage. Thirty-two (60-day-old) barrows, weighing 20.20 ± 1.34 kg, were used in a randomized block design consisting of eight animals with four treatment regimens. Treatments consisted of: Control = no dietary antioxidant; butylated hydroxytoluene (BHT) = diet with 200 ppm BHT; EEMS200 = diet with 200 ppm EEMS; EEMS400 = diet with 400 ppm EEMS. At 145 days of age and average weight of 95.47 ± 6.19 kg, the animals were slaughtered and loin samples were collected and frozen before for qualitative analysis and evaluation of the effect of subsequent storage for 1 or 7 days at 8 °C on lipid stability, SG-NP, phenolic compounds, total antioxidant capacity and total antioxidant activity Meat from animals fed EEMS400 diet showed lower cooking loss (P < 0.0001) and higher non-protein sulfhydryl groups, phenolic compounds and total antioxidant activity at both 1 and 7 days of storage (P < 0.0001) compared to the other treatments. Greater antioxidant capacity was observed at 1 day storage in the meat of animals that consumed EEMS regardless of concentration when compared to the control group (P < 0.01). The dietary inclusion of EEMS to pig diets is more effective at 400 ppm in improving meat quality after cooking and antioxidant parameters of pork.

Protective effect of standardised fruit extract of Garcinia cowa Roxb. ex Choisy against ethanol induced gastric mucosal lesions in Wistar rats

Background and aim The fruit of Garcinia is a rich and valuable source of bioactive compounds and is traditionally used for treating wounds and ulcers. The present study was carried out to investigate the protective effect of chromatographically standardized fruit extract of Garcinia cowa (GCE) on ethanol-induced gastric lesions in rats and its possible mechanisms. Methods The effect of GCE (200 and 400 mg/kg body weight) was evaluated by determining various gastric ulcer parameters like gastric wall mucus, non-protein sulfhydryls (NP-SH) content, microvascular permeability, endogenous antioxidant enzyme, and gastric histopathological study. Results and conclusions Oral administration of GCE at doses of 200 and 400 mg/kg exhibited significant (p < .01) dose-dependent inhibition of ulcer index by 18.94–44.02%, respectively. Pre-treatment of rats with GCE (400 mg/kg) significantly restored the depleted gastric wall mucus level by 34.09% and NP-SH content by 33.35% induced by ethanol administration. In addition, GCE (400 mg/kg) showed a significant decrease in microvascular permeability of Evans Blue by 47.43%, rationalizing its protective effect. Furthermore, a significant increase in oxidative enzyme levels with reduction in malondialdehyde level and elevation of superoxide dismutase (SOD) activity was observed in the GCE treated group as compared to the ulcer control group. The histopathological assessment also confirmed the protective nature of GCE. HPTLC analysis showed the presence of 0.27%, 0.11% w/w gallic acid, and amentoflavone, respectively in GCE. The content of α-mangostin and xanthochymol in the G. cowa extract sample quantified by HPLC-PDA method was 0.72 and 8.46%, respectively. The results obtained indicate that the protective effect of GCE against gastric ulcers in rats through multiple actions confirmed by the reduction of oxidative stress and restoration of adhered gastric mucus, NP-SH content, and histological architecture. KEY MESSAGES Ethanol is the most typical ulcerogenic agent and has been shown to extend the risk of ulcer in humans. Natural products are promising alternative medication for the development of new drugs to regulate gastrointestinal diseases. Garcinia cowa protects the gastric mucosa through multiple actions that include restoration of adhered gastric mucus and inhibition of lipid peroxidation.

EFFECT OF COMPOSITE DRUG ETHYLTHIOSULPHONATE WITH SURFACTANT RAMNOLIPID BIOCOMPLEX ON SH-GROUP CONTENT IN DAPHNIA MAGNA

One of the main obstacles to the use of thiosulfonates in aquaculture is their insolubility in water. This problem is eliminated by using a composition based on ethylthiosulfanilate (ETS) and surface-active rhamnolipid biocomplex (RBC) of bacteria of the genus Pseudomonas, which provides increased bioavailability of ethylthiosulfanilate and activation of biocidal properties of the drug. However, this may increase the toxic effects of the created composition. Given the possibility of using Daphnia magna Straus in the procedure of bioencapsulation as a vector organism for the delivery of a composite drug, a study of the effect of ETS: RBC in nontoxic concentrations (2.5·10-3 mg / ml and 5·10-3 mg / ml (by ETS) on the content of protein and non-protein thiols in Daphnia magna, as well as the activity of enzymes inhibited by a natural analogue of thiosulfonates - allicin. A decrease in the content of protein and non-protein thiols in the tissues of Daphnia magna was found under the action of both studied concentrations of the drug. A significant reduction in non-protein SH groups compared to protein-bound ones may indicate the active and efficient involvement of glutathione ethylthiosulfanilate, which is the predominant non-protein thiol in the cell and provides protection against oxidation of functional groups of proteins and enzymes. The established inhibition of superoxide dismutase activity may be due to S-thioallylation of ethylthiosulfanilate SH-containing amino acids in the structure of the enzyme. No significant changes in glutathione-S-transferase activity under the action of the study drug were observed. Only when using a higher concentration of the composite drug ETS: RBC begins to show a tendency to decrease activity, most likely due to a decrease in the content of reduced glutathione under these conditions. Given the survival rates of Daphnia magna under the conditions of using the composite drug ETS: RBC at concentrations of 2.·10-3 mg / ml and 5·10-3 mg / ml, it is likely that its effect focuses on reactions involving sulfhydryl groups and does not cause significant changes in the detoxification system of the cell.

Effects of single and binary applications of bisphenol A and NaCl on Ceratopyllum demersum

Determining the physiological effects of single and binary applications of BPA and NaCl on the Ceratophyllum demersum L., which is a rootless submerged aquatic macrophyte, is the aim of the present study. For this purpose, the macrophyte was collected from a local pond that was not exposed to any pollution. Macrophytes were acclimatized in 10% nutrient solution for 14 days, than they were treated with 17.2 mg/L BPA; 10 and 100 mM NaCl; 17.2 mg/L BPA plus 10 mM NaCl and 17.2 mg/L BPA plus 100 mM NaCl. The macrophyte without added BPA or/and NaCl served as control (without treatment). Increasing concentrations of NaCl induced a progressive accumulation of Na in the macrophyte tissues. On the other hand, BPA application partially reduced Na uptake. Nutrient uptake was affected differently by the applications. The contents of some nutrients such as Cu, Zn, Mn, K and Mg were generally reduced, whereas the Fe and Ca contents were increased. In general, increases in contents of total carbohydrate, total phenolic and non-protein sulfhydryl groups were found, when compared to control. Protein and photosynthetic pigment contents, on the contrary to these, were decreased. According to findings, the increase in H2O2 and MDA levels showed that single and combined applications of BPA and NaCl in C. demersum tissues induced oxidative stress.

Gastroprotective effect of Lycium barbarum polysaccharides and C-phycocyanin in rats with ethanol-induced gastric ulcer

This study investigated the gastroprotective effect of Lycium barbarum polysaccharides (LBP) and C-phycocyanin (C-PC) in rats with ethanol-induced gastric ulcer. Rats were divided into 5 groups: normal, ulcer, ulcer treated with 100 mg/kg bw LBP, ulcer treated with 50 mg/kg bw C-PC, and ulcer treated with 50 mg/kg bw LBP and 25 mg/kg bw C-PC. Pretreatment with LBP and/or C-PC was given a week before ulcer induction. Ulcer induction was produced by 50% ethanol administration orally every other day for 4 weeks. After 5-week treatment, the histopathological observation showed that LBP or C-PC attenuated the severity of gastric mucosal damage. LBP decreased serum malondialdehyde (MDA) levels and gastric interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) levels, and myeloperoxidase (MPO) activity. C-PC decreased serum MDA levels and gastric tumor necrosis factor-α (TNF-α), IL-1β, IL-6, ICAM-1 levels, and MPO activity. Combined LBP and C-PC decreased serum MDA levels and gastric TNF-α, IL-1β, IL-6, and ICAM-1 levels. LBP and/or C-PC increased gastric heat shock protein 70 and non-protein sulfhydryl compounds. Rats with ulcer and treatment had enriched with the family Bacillaceae. Therefore, pretreatment with LBP and/or C-PC attenuated ethanol-induced gastric ulcer in rats via suppressing oxidation and inflammation and increasing gastroprotection.

Chromium metabolism characteristics of coexpression of ChrA and ChrT gene

ObjectiveSerratia sp. S2 is a wild strain with chromium resistance and reduction ability. Chromium(VI) metabolic-protein-coding gene ChrA and ChrT were cloned from Serratia sp. S2, and ligated with prokaryotic expression vectors pET-28a (+) and transformed into E. coli BL21 to construct ChrA, ChrT and ChrAT engineered bacteria. By studying the characteristics of Cr(VI) metabolism in engineered bacteria, the function and mechanism of the sole expression and coexpression of ChrA and ChrT genes were studied. MethodsUsing Serratia sp. S2 genome as template, ChrA and ChrT genes were amplified by PCR, and prokaryotic expression vectors was ligated to form the recombinant plasmid pET-28a (+)-ChrA, pET-28a (+)-ChrT and pET-28a (+)-ChrAT, and transformed into E. coli BL21 to construct ChrA, ChrT, ChrAT engineered bacteria. The growth curve, tolerance, and reduction of Cr(VI), the distribution of intracellular and extracellular Cr, activity of chromium reductase and intracellular oxidative stress in engineered bacteria were measured to explore the metabolic characteristics of Cr(VI) in ChrA, ChrT, ChrAT engineered bacteria. ResultsChrA, ChrT and ChrAT engineered bacteria were successfully constructed by gene recombination technology. The tolerance to Cr(VI) was Serratia sp. S2 > ChrAT ≈ ChrA > ChrT > Control (P < 0.05), and the reduction ability to Cr(VI) was Serratia sp. S2 > ChrAT ≈ ChrT > ChrA (P < 0.05). The chromium distribution experiments confirmed that Cr(VI) and Cr(III) were the main valence states. Effect of electron donors on chromium reductase activity was NADPH > NADH > non-NAD(P)H (P < 0.05). The activity of chromium reductase increased significantly with NAD(P)H (P < 0.05). The Glutathione and NPSH (Non-protein Sulfhydryl) levels of ChrA, ChrAT engineered bacteria increased significantly (P < 0.05) under the condition of Cr(VI), but there was no significant difference in the indexes of ChrT engineered bacteria (P > 0.05). ConclusionChrAT engineered bacteria possesses resistance and reduction abilities of Cr(VI). ChrA protein endows the strain with the ability to resist Cr(VI). ChrT protein reduces Cr(VI) to Cr(III) by using NAD(P)H as electronic donor. The reduction process promotes the production of GSH, GSSG and NPSH to maintain the intracellular reduction state, which further improves the Cr(VI) tolerance and reduction ability of ChrAT engineered bacteria.

Effect of Berberine on Glycation, Aldose Reductase Activity, and Oxidative Stress in the Lenses of Streptozotocin-Induced Diabetic Rats In Vivo-A Preliminary Study.

Diabetes mellitus affects the eye lens, leading to cataract formation by glycation, osmotic stress, and oxidative stress. Berberine, an isoquinoline alkaloid, is a natural compound that has been reported to counteract all these pathological processes in various tissues and organs. The goal of this study was to evaluate whether berberine administered at a dose of 50 mg/kg by oral gavage for 28 days to rats with streptozotocin-induced diabetes reveals such effects on the biochemical parameters in the lenses. For this purpose, the following lenticular parameters were studied: concentrations of soluble protein, non-protein sulfhydryl groups (NPSH), advanced oxidation protein products (AOPP), advanced glycation end-products (AGEs), thiobarbituric acid reactive substances (TBARS), and activities of aldose reductase (AR), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Diabetes induced unfavorable changes in the majority of the examined parameters. The administration of berberine resulted in an increased soluble protein level, decreased activity of AR, and lowered AOPP and AGEs levels. The results suggest that berberine administered orally positively affects the lenses of diabetic rats, and should be further examined with regard to its anticataract potential.

Gastroprotective effect of the alkaloid boldine: Involvement of non-protein sulfhydryl groups, prostanoids and reduction on oxidative stress

Boldine is the main alkaloid of Peumus boldus Molina, widely used in the traditional medicine for the treatment of digestive disorders. It is a compound with excellent antioxidant and anti-inflammatory properties already described. Despite the widespread use of P. boldus for digestive disorders treatment, the gastroprotective effect of Boldine remains unknown. Considering the need for new approaches to treat gastric ulcers with fewer side effects than current therapy, this study aimed to investigate the gastroprotective effect of Boldine in mice, as well as the mechanisms underlying this effect. The gastroprotective effect of Boldine was evaluated on gastric ulcer induced by 60% ethanol/0.3 M HCl or indomethacin (100 mg/kg) in mice. Histological analysis and the mucin-like glycoprotein content were evaluated in ethanol-ulcerated tissue, as well as, oxidative stress and inflammatory parameters. The mechanisms involved in the effect of Boldine were evaluated by pretreating mice with NEM (a sulfhydryl group chelator, 10 mg/kg, i.p.), l-NAME (a non-selective nitric oxide synthase inhibitor, 70 mg/kg, i.p.), yohimbine (an alpha-adrenergic receptor antagonist, 2 mg/kg, i.p.) and indomethacin (a cyclooxygenase inhibitor, 10 mg/kg, i.p.). In addition, the in vitro effect of Boldine on H+/K+-ATPase activity was determined. Boldine was able to protect gastric mucosa against the damage induced by ethanol/HCl and indomethacin, as evidenced by reduced lesion area and histological analysis. Moreover, the alkaloid reduced oxidative stress and inflammatory mediators in ethanol-ulcerated tissue, beyond has increased mucin-like glycoprotein amount. Finally, Boldine effect is dependent on non-protein sulfhydryl groups and prostanoids but does not involve the inhibition of H+/K + -ATPase activity, being a promising natural resource for gastric ulcer treatment.

Protective effect of lyophilized sapodilla (Manilkara zapota) fruit extract against CCl4-induced liver damage in rats.

The tropical fruit sapodilla (Manilkara zapota syn. Achras zapota) is a rich source of nutrients, minerals and a myriad of bioactive phytochemicals such as flavonoids and catechins. Pharmacologically, sapodilla has been shown to exhibit anti-bacterial, anti-parasitic, anti-fungal, antiglycative, hypocholesterolemic and anti-cancer effects. However, its influence on hepatic tissue and serum lipids remains obscure. To address this, we used an in vivo model of liver damage to elucidate the effect of lyophilized sapodilla extract (LSE) treatment in carbon tetra chloride (CCl4) intoxicated rats. Exposure of CCl4 resulted in elevation of serum biomarkers of liver damage (aspartate transaminase, alanine aminotransferase, γ-glutamyl transferase and alkaline phosphatase), bilirubin and dysregulation of serum lipid profile (cholesterol and triglycerides). These effects were significantly and dose-dependently reversed by LSE treatment (250 and 500 mg/kg). Administration of LSE also reduced the structural damage caused by CCl4 in the liver. Furthermore, determination of oxidative stress parameters (malondialdehyde and non-protein sulfhydryls) revealed that LSE treatment mitigated CCl4-triggered modulation of both molecules. LSE also showed a strong antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and β-carotene-linoleic acid assays. In conclusion, the present study discloses the hepatoprotective and lipid-lowering effects of lyophilized sapodilla extract against CCl4-induced liver damage, an effect, at least in part, mediated by its antioxidant activity.

Вплив 2-(3-аліл-4-оксо-3,4-дигідро-хіназолін- 2-іл-сульфоніл)-N-(2,6-дихлорфеніл)-цераміду на складові хроматину та стан антиоксидантної системи в саркомі 45 і незмінених тканинах шкіри щурів

Стрімке поширення онкологічних захворювань у ХХІ столітті в усьому світі зумовлює інтенсифікацію хіміотерапевтичного лікування даної патології зі застосуванням усе нових і нових цитотоксичних і цитостатичних агентів. Однак це зумовлює зростання й числа побічних ефектів і небажаних наслідків використання даних препаратів. Неспецифічна дія щодо всього організму пацієнта та висока токсичність даної групи лікарських засобів, зокрема, їхня кардіо-, нефро- та нейротоксичність, а також відсутність достатньої інформації щодо віддалених наслідків введення протипухлинних засобів на стан прилеглих тканин, які не були захоплені інвазією пухлини, зумовлюють нагальну потребу в системному вивченні біохімічних змін не лише в пухлині, але й поза її межами. У попередніх експериментах нами було проведене вивчення впливу протипухлинного похідного хіназоліну на складові хроматину, процеси фрагментації ДНК, вміст небілкових і пов’язаних з білками SH-груп у карциномі Герена та незмінених тканинах матки й виявлено специфічність його впливу на низку показників виключно в тканині пухлини. У зв’язку з цим актуальним є з’ясування, чи є виявлена специфічність похідного хіназоліну характерною лише для тканини матки, чи вона поширюється й на інші тканини організму. Мета дослідження – вивчити вплив 2-(3-аліл-4-оксо-3,4-дигідро-хіназолін-2-іл-сульфоніл)-N(2,6-дихлорфеніл)-цераміду (АХДЦ) на ДНК, РНК, білки хроматину, процеси фрагментації ДНК, вміст небілкових і пов’язаних з білками SH-груп у саркомі 45 і незмінених тканинах шкіри щурів. Тварини були розподілені на 3 групи по 6 тварин у кожній: 1 – інтактні щури; 2 – негативний контроль (саркома 45); 3 – саркома 45 + АХДЦ (29,93 мг/кг). Вивчення впливу АХДЦ на ДНК, РНК, білки хроматину, процеси фрагментації ДНК, вміст небілкових і пов’язаних з білками SH-груп у саркомі 45 і незмінених тканинах шкіри показало, що дана сполука вірогідно змінювала більшість досліджуваних показників як порівняно з інтактними тваринами, так і з саркомою 45 без лікування. Специфічність впливу АХДЦ на клітини пухлин була найвираженішою щодо ДНК-фрагментації та змін вмісту РНК, співвідношень РНК/ДНК і РНК/НК. Щодо впливу на вміст SH-груп у тканині саркоми 45 і неуражених пухлиною тканинах шкіри, то в даному випадку ефект АХДЦ був протилежним за напрямком стосовно змін вмісту небілкових і пов’язаних з білками SH-груп.

Impact of date palm pollen (Phoenix dactylifera) treatment on paracetamol-induced hepatorenal toxicity in rats

BackgroundConsumption of plant-derived nutraceuticals and crude drugs in Arab traditional medicine is widely believed to confer beneficial effects in liver and kidney diseases. Fruits from the date palm Phoenix dactylifera L. are a rich source of nutrients and bioactive phytochemicals which possess a myriad of pharmacological effects. Herein, we examined the impact of Date Palm Pollen (DPP) aqueous suspension treatment on paracetamol (APAP) [Acetaminophen (APAP)] triggered hepatorenal damage in rats and further explored the underlying putative mechanism.MethodsThirty Wistar rats were assigned to five groups (n = 6/group). Group I was control group; animals in group II were administered APAP 1000 mg/kg body weight (b.w.) intraperitonealy (i.p.); Group III and IV administered APAP plus date palm pollen with doses of 50, 100 mg/kg b.w and group V were administered APAP plus Silymarin (SIL) 10 mg/kg b.w. (i.p) respectively. Various biochemical parameters and histological assessment were evaluated in serum and tissue homogenate.ResultsPretreatment with DPP aqueous suspensions (50 and 100 mg/kg b.w.) significantly (p < 0.05) thwarted APAP triggered alterations in serum biomarkers of liver damage [aspartate transaminase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP)], serum albumin as well as bilirubin. DPP treatment further mitigated APAP triggered dyslipidemia associated with hepatic damage by influencing APAP elicited changes in serum levels of cholesterol, triglycerides, HDL, LDL and VLDL. DPP treatment significantly (p < 0.05) ameliorated extrahepatic manifestations of APAP toxicity by influencing alterations in parameters of renal function (creatinine, urea and uric acid) as well serum electrolytes (Sodium, Potassium and Calcium). DPP treatment further influenced APAP-induced histological lesions by curtailing necrosis and inflammatory changes in the hepatic and renal architecture, respectively. Furthermore, DPP treatment modulated APAP-induced redox imbalance in the hepatic and renal tissue by blunting the increase of malondialdehyde (MDA) as well as decrease of nonprotein sulfhydryls (NP-SH) significantly (p < 0.05) when compared with control. The protective effect of DPP was further confirmed histologically.ConclusionsThe present observations point to an hepatorenal protective effects of acute DPP treatment in APAP-intoxicated rats which is underpinned by its robust antioxidant properties.

Ефект етил 2-(хіназолін-4-іламіно)-4,5,6,7тетрагідробензо[ b ]тіофен-3-карбоксилат гідрохлориду на ДНК, РНК, білки хроматину й показники стану антиоксидантної системи в карциномі Герена та незмінених тканинах матки щурів

Стандартні підходи до вивчення специфічної фармакологічної дії та токсичності протипухлинних засобів не дають змоги провести детальну комплексну оцінку метаболічних змін поза пухлиною, хоча давно стало очевидним, що неспецифічна дія хіміотерапії може на тлі пригнічення росту пухлин викликати незворотні зміни в організмі, які надалі суттєво погіршать його шанси на видужання. Ці обставини зумовлюють актуальність включення в доклінічні дослідження нових протипухлинних засобів вивчення їхніх ефектів як на пухлини, так і на прилеглі не уражені тканини, для подальшої оптимізації хіміотерапії. Мета дослідження – порівняти вплив етил 2-(хіназолін-4-іламіно)-4,5,6,7-тетрагідробензо[b] тіофен-3-карбоксилат гідрохлориду (ЕХТК) на ДНК, РНК, білки хроматину, процеси фрагментації ДНК, вміст ТБК-реактантів і SН-груп у карциномі Герена та незмінених тканинах матки. Дослідження впливу ЕХТК проводили на білих щурах – самицях лінії Вістар. Тварини були розподілені за методом рандомізації на 3 групи по 6 тварин у кожній: 1 – інтактні щури; 2 – позитивний контроль (карцинома Герена); 3 – карцинома Герена + ЕХТК (24,37 мг/кг). Вивчення впливу ЕХТК на ДНК, РНК, білки хроматину, процеси фрагментації ДНК, вміст ТБКреактантів та небілкових і пов’язаних з білками SH-груп у карциномі Герена та незмінених тканинах матки показало, що дана сполука вірогідно змінювала більшість досліджуваних показників як порівняно з інтактними тваринами, так і з карциномою Герена без лікування. Ефект ЕХТК на фрагментацію ДНК не відзначався вузькою тканинною специфічністю. Специфічність впливу ЕХТК на клітини пухлин була найвираженішою у випадку змін вмісту ДНК, РНК, білків хроматину, а також ТБК-реактантів, небілкових і пов’язаних з білками SH-груп.

The gastroprotective effect of the foxtail millet and adlay processing product against stress-induced gastric mucosal lesions in rats

Foxtail millet (Setaria italica (L.) P. Beauv.) and adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) seeds have substantial benefits possesses remarkable edible and nutritive values, and ease of processing and food manufacturing. They have nutraceutical properties in the form of antioxidants which prevent deterioration of human health and have long been used in traditional Chinese medicine as a remedy for many diseases. The present study is designed to investigate the gastroprotective effect of foxtail millet and adlay processing product (APP) diet on water immersion restraint stress (WIRS) induced ulceration in rats. We examined the effects of intake of AIN-93G diet containing either foxtail millet (10, 20 and 40%, 4 weeks) or APP (15 and 30%, 5 weeks) on macroscopic ulcer index (UI), plasma calcium level, lipid peroxidation products (estimated by the thiobarbituric acid reactive substances; TBARS), non-protein sulfhydryl (NPSH), digestive enzyme activities, and histopathology were determined. The results showed that pretreatment with millet and adlay diets significantly prevented the gastric mucosal lesion development. In addition, ulcerated rats showed depletion of NPSH levels whereas treatment with millet and adlay reverted this decline in stress-induced rats. Histological studies confirmed the results. The finding suggests that millet and adlay diets promote ulcer protection by the decrease in ulcer index, TBARS values and increase NPSH concentrations. Millet and adlay diets retain the advantage of being a natural product which may protect the gastric mucosa against ulceration.

Вплив Іфітинібу на складові хроматину та стан антиоксидантної системи в карциномі Герена та незмінених тканинах матки

Неспецифічна дія протипухлинної хіміотерапії на прилеглі до пухлини тканини сама по собі здатна погіршити стан організму додатково до наслідків розвитку неопластичного процесу і навіть справити вирішальну роль у виживанні організму. Тому актуальним є проведення паралельних досліджень впливу нових протипухлинних засобів на етапі доклінічних випробувань як на пухлини, так і на тканини того самого організму, які неуражені неопластичним процесом, для подальшої оптимізації хіміотерапії. Мета дослідження – вивчити вплив Іфітинібу на ДНК, РНК, білки хроматину, процеси фрагментації ДНК, вміст небілкових і пов’язаних з білками SH-груп у карциномі Герена та незмінених тканинах матки. Дослідження впливу Іфітинібу проводили на білих щурах-самицях лінії Вістар. Тварини були розподілені за методом рандомізації на 3 групи по 6 тварин у кожній: 1 – інтактні щури, 2 – негативний контроль (карцинома Герена), 3 – карцинома Герена + 29,93 мг/кг Іфітинібу. Вивчення впливу Іфітинібу на ДНК, РНК, білки хроматину, процеси фрагментації ДНК, вміст небілкових і пов’язаних з білками SH-груп у карциномі Герена та незмінених тканинах матки показало, що даний препарат вірогідно змінював більшість досліджуваних показників як порівняно з інтактними тваринами, так і з карциномою Герена без лікування. Специфічність впливу Іфітинібу на клітини пухлин була найвираженішою у випадку ДНК-фрагментації та змін вмісту небілкових і пов’язаних з білками SH-груп.

ОКИСНА МОДИФІКАЦІЯ БІЛКІВ У СИРОВАТЦІ КРОВІ ЩУРІВ ЗА УМОВ ЕКСПЕРИМЕНТАЛЬНОГО ОСТЕОАРТРИТУ ТА СУМІСНОГО ВВЕДЕННЯ ХОНДРОПРОТЕКТОРА ТА МУЛЬТИПРОБІОТИКА

One of the actual problems of modern medicine is joint disease. Among them, osteoarthritis occupies an important place. The formation of osteoarthritis is accompanied by the development of inflammation, which leads to damage to all structures of the joint. An important role in inflammatory processes is played by the intensification of free radical processes. As the disease develops, the joints lose their mobility, which leads to a decrease in the quality of life of patients and the development of disability. In this regard, it is important to search for drugs that have regenerative, anti-inflammatory and antiradical properties. The aim of our study was to investigate the combined effect of chondroitin sulfate and multiprobiotic on the content of oxidative protein modification products and the level of sulfhydryl groups in rat blood serum under conditions of monoiodoacetate-induced osteoarthritis. The study included participation of white male non-linear rats (weighing 180–240 g) adherence to the general ethical principles of animal experiments. An experimental osteoarthritis model was created by introducing 1 mg of sodium monoiodoacetate into the knee ligament. Chondroitin sulfate and multiprobiotic were used as therapeutic agents. The content of products of oxidative modification of proteins was determined by the level of carbonyl derivatives, which are manifested in the reaction with 2,4-dinitrophenylhydrazine. The level of total, protein-bound and non-protein sulfhydryl groups was measured by the Elman method. It was found that under conditions of monoiodoacetate-induced osteoarthritis in the blood serum of rats, the content of products of oxidative modification of proteins increases. The level of neutral aldehyde products (E max = 356 nm) is increased by 2.5 times and neutral ketone products (E max = 370 nm), respectively, by 2,1 times compared to the control. Under the same experimental conditions in the blood serum, the amount of basic aldehyde products (E max = 430 nm) increases by 1.9 times, while the content of the main ketone products (E max = 530 nm) increases by 1,7 times compared to the control groups. In experimental osteoarthritis in the blood serum, the content of sulfhydryl groups decreases: non-protein SH-groups – 1,5 times, protein and general SH-groups – 1,7 times relative to the control. This indicates disturbance of the oxidative-antioxidant balance and the development of oxidative stress in the organism during experimental osteoarthritis. It was shown that the combined administration of chondroitin sulfate and multiprobiotics in animals with experimental osteoarthritis partially restored the above parameters.