Water-soluble Form Of Quercetin Research Articles

Changes in the biochemical parameters of blood and the morphological structure of the pancreas in rats with acute pancreatitis and their correction using corvitin

Acute pancreatitis (AP) is an inflammation of the pancreas characterized by a severe course and a high mortality rate. The pathogenesis of AP is still not fully understood, so there is currently a lack of treatment. Corvitin is a water-soluble form of quercetin that retains all the properties of quercetin and has powerful antioxidant, anti-inflammatory and anti-apoptotic properties. The aim of our study was to evaluate the effect of corvitin on biochemical blood parameters and morphological features of the pancreas in rats with AP caused by intraperitoneal administration of L-arginine (200 mg/100 g). This model of AP is non-invasive, highly reproducible and causes selective, dose-dependent necrosis of acinar cells and is ideal both for studying the pathomechanisms of AP and for observing and influencing changes in the course of the disease. The legality of using this model is confirmed by the morphostructural changes in the pancreas that are characteristic of AP. In rats with AP, an increase in the blood concentration of α-amylase (twice), alanine aminotransferase (ALT) (three times), aspartate aminotransferase (AST) (one and a half times) compared to control values was observed already on the first day of the pathology development. On the second day of AP, the level of glucose and urea in the blood of rats increased by 34 and 22%, respectively, while the creatinine content did not change. Under the influence of corvitin (50 mg/kg), the levels of α-amylase, ALT and glucose decreased already after a day, while the content of AST and urea increased and remained so until the 8th day of observation. The most positive dynamics of morphological changes in the pancreas of rats was observed when corvitin was used on the first day of AP induction.

EFFECT OF TRANSCRIPTION FACTOR MODULATORS ON OXIDATIVE-NITROSATIVE STRESS INDICATORS IN TISSUES OF THE SMALL INTESTINE OF RATS AFTER LAPARATOMY UNDER LIPOPOLYSACCHARIDE-INDUCED SYSTEMIC INFLAMMATORY RESPONSE

This study is devoted to investigating the effect of NF-κB and Nrf2 transcription factor modulators on oxidative-nitrosative stress indicators in the tissues of the small intestine of rats after abdominal surgical trauma (laparotomy) under lipopolysaccharide (LPS)-induced systemic inflammatory response (SIR). The study was performed on 35 Wister white male rats weighing 220-250 g, divided into 5 groups: the 1st (control) group included "sham-operated" animals; the 2nd group involved rats, who underwent laparotomy following the LPS-induced SIR modelling; the animals of the 3rd, 4th and 5th groups subjected to laparotomy following LPS-induced SIR and then for 7 days received ammonium pyrrolidine dithiocarbamate, an NF-κB activation inhibitor, in a dose of 76 mg/kg intraperitoneally, dimethyl fumarate, an Nrf2 inducer, in a dose of 15 mg/kg in 10% dimethyl sulfoxide solution, and a water-soluble form of quercetin in a dose of 100 mg/kg that is 10 mg/kg in terms of quercetin, respectively. The measurements were carried out in 7 days after the “sham” surgical operation and laparotomy. It has been found out that the use of ammonium pyrrolidine dithiocarbamate, dimethyl fumarate, and water-soluble form of quercetin in case of the combined effects of surgical trauma (laparotomy) and LPS S. typhi significantly restrains the production of superoxide anion radical by various sources (microsomes and constitutive isoforms of NO-synthase, leukocyte NADPH-oxidase), total and inducible NO-synthase activity, formation of peroxynitrite in the tissues of the small intestine of rats. The study has also demonstrated the ability of dimethylfumarate, unlike ammonium pyrrolidine dithiocarbamate and quercetin, to improve the constitutive synthesis of nitric oxide under experimental conditions.

EFFECT OF TRANSCRIPTION FACTOR MODULATORS ON CARBOHYDRATES AND LIPID METABOLISM IN RATS AFTER LAPARATOMY UNDER LIPOPOLYSACCHARIDE-INDUCED SYSTEMIC INFLAMMATORY RESPONSE

This study is devoted to investigating the effect of NF-κB and Nrf2, transcription factor modulators, on markers of surgical stress and acute phase response, carbohydrate and lipid metabolism in the case of abdominal surgical trauma (laparotomy) under lipopolysaccharide (LPS)-induced systemic inflammatory response (SIR). The study was performed on 28 white Wistar male rats weighing 220-250 g, divided into 4 groups: 1st (control) included "pseudo-operated" animals; 2nd group involved rats, who underwent laparotomy following the LPS-induced SIR modelling; the animals of the 3rd, 4th and 5th groups subjected to laparotomy following LPS-induced SIR then for 7 days received ammonium pyrrolidinedithiocarbamate, an NF-κB activation inhibitor, in a dose of 76 mg/kg, dimethyl fumarate, an N inducer, in a dose of 15 mg / kg in 10% dimethyl sulfoxide solution, and a water-soluble form of quercetin in a dose of 100 mg/kg that is 10 mg/kg in terms of quercetin. The measurements were carried out in 7 days after the false surgical operation or laparotomy. It has been found out that the use of ammonium pyrrolidine dithiocarbamate, dimethyl fumarate, and water-soluble form of quercetin under the combined effects of surgical trauma (laparotomy) and S. typhi LPS significantly reduces the concentration of cortisol in blood plasma and the content of ceruloplasmin in the blood serum, lowers the level of hyperglycemia and hypertriacylglycerolemia.

EFFECT OF WATER-SOLUBLE QUERCETIN ON INDICATORS OF OXIDATIVE-NITROSATIVE STRESS IN TISSUES OF SUBMANDIBULAR SALIVARY GLANDS OF RATS UNDER LIPOPOLYSACCHARIDE-INDUCED SYSTEMIC INFLAMMATORY RESPONSE

The aim of this study was to investigate the effect of the water-soluble form of quercetin on the indicators of oxidative-nitrosative stress in the tissues of the submandibular salivary glands (SG) under conditions of lipopolysaccharide-induced systemic inflammatory response (SIR). The study was performed on 30 white Wistar male rats weighing 180-220 g, divided into 3 groups: 1st group included intact animals, 2nd group included animals, subjected to the systemic administration of lipopolysaccharide of Salmonella typhi, 3rd group involved animals, which received water-soluble quercetin complex with polyvinylpyrrolidone (corvitin) in a dosage of 100 mg/kg (10 mg/ g in terms of quercetin) intraperitoneally every 3 days, starting on the 30 day of the experiment with using S. typhi lipopolysaccharide. The latter was administered in a dose of 0.4 μg/kg body weight 3 times during the 1st week, and then once a week for the next 7 weeks. The study has demonstrated that applying quercetin under SIR restrains the production of reactive oxygen species in SG tissues: it reduces unstimulated production of superoxide anion radical and its induced generation with the administration of NADPH (by microsomes and NO-synthase), NADH (by mitochondria), S. typhi lipopolysaccharide (by leukocyte NADPH-oxidase). The administration of quercetin under SIR condition diminishes the signs of nitrosative stress in SG tissues, as evidenced by decrease in inducible NO-synthase activity without significant changes in ornithine decarboxylase activity and the level of coupling of constitutive isoform of NO-synthase, decreased concentration of highly active peroxynitrite, but, however, without significant shift in S-nitrosothiols content.

CHANGES IN BEHAVIOURAL REACTIONS OF RATS FOLLOWING MODELLED TRAUMATIC BRAIN INJURY AND THEIR CORRECTION WITH TRANSCRIPTION FACTORS MODULATORS

This study aimed at investigating the effect of modulators of transcription factors NF-κB, AP-1 and Nrf2 on the behavioural responses of rats in the "Dark-light chamber" and "Open field" tests following the simulation of traumatic brain injury (TBI). The study included 42 white Wistar male rats weighing 180-220 g, divided into 6 groups of 7 rats in each: the control group included the animals exposed to the above mentioned tests before TBI modelling and 3 – 7 days after it; as for the animals of other groups, for 7 days after TBI simulation they were given intraperitoneal injections of the following transcription factor modulators: ammonium pyrrolidine dithiocarbamate, an inhibitor of nuclear translocation NF-κB, was injected in a dose of 76 mg/kg; AP-1 SR 11302 inhibitor given in a dose of 1 mg/kg; Nrf2 inductors as dimethyl fumarate given in a dose of 15 mg/kg of a 10% dimethyl sulfoxide solution and epigallocatechin-3-gallate in a dose of 1 mg/kg as well as a water-soluble form of quercetin (corvitin), which acts as an NF-κB inhibitor and Nr inducer, in a dose of 100 mg / kg (10 mg / kg in terms of quercetin). Unlike the test animals, the rats of the control group were given intraperitoneal injections of 1 ml of isotonic sodium chloride solution. It has been found out that during the first week following TBI simulation, the locomotor activity and psycho-emotional state of the rats were disturbed: the indicators of motor and exploratory activity, orienting reaction became deteriorated, anxiety and fear increased as well as the frequency of self-grooming actions. The use of inhibitors of transcription factors NF-κB (ammonium pyrolidindithiocarbamate) and AP-1 (SR 11302), Nrf2 inducers (dimethyl fumarate and epigallocatechin-3-gallate) and the water-soluble form of quercetin (corvitin) for the 1st week after TBI simulation improves motor performance and exploratory activity, orienting reaction, and reduces emotional anxiety and fear as well.

EFFECTS OF MODULATORS OF REDOX-SENSITIVE TRANSCRIPTION FACTORS ON NEUROLOGIC DEFICIT IN RATS AFTER TRAUMATIC BRAIN INJURY

This study was aimed as investigating the effects of modulators of transcription factors NF-κB, AP-1 and Nrf2 on the survival rate of white rats and the development of neurological deficits following the simulation of traumatic brain injury (TBI). The study included 110 white Wistar male rats weighing 180-220 g, divided into 6 groups. Control group involved animals after the TBI injury simulation (n=30). The animals of other groups (16 rats in each) were intraperitoneally injected with modulators of transcription factors after the simulation of the trauma for 7 days: ammonium pyrrolidine dithiocarbamate, an inhibitor of nuclear translocation NF-κB, was injected in a dose of 76 mg/kg; AP-1 SR 11302 inhibitor – in a dose of 1 mg/kg; Nrf2-ARE system inductors as dimethyl fumarate in a dose of 15 mg/kg in a 10% dimethyl sulfoxide solution and epigallocatechin-3-gallate in a dose of 1 mg/kg. The test animals were also injected with a water-soluble form of quercetin (corvitin), which acts as an NF-κB inhibitor and Nrf2 inducer, in a dose of 100 mg/kg (10 mg/kg in terms of quercetin). The animals in the control group were injected intraperitoneally with 1 ml of isotonic sodium chloride solution instead of the tested compounds mentioned above. It has been found out that on the 7th day after the simulation of moderate TBI most animals showed signs of neurological deficit including impaired muscle tone (83.3%), impaired coordination (83.3%) and pain reaction (66.7%). Integral indicator of neurological deficit by Todd et al. 100-score grading scale was 51.33±2.95. The use of inhibitors of transcription factors NF-κB (ammonium pyrrolidinedithiocarbamate) and AP-1 (SR 11302), the Nrf2-ARE system inducers (dimethylfumarate and epigallocatechin-3-gallate) and the water-soluble form of quercetin (corvitin) increases rats’ survival rate, significantly limits their signs of neurological deficit and its integral index.

COMBINED EFFECTS OF QUERCETIN AND MODULATORS OF REDOX SENSITIVE FACTORS ON THE INDICATORS OF SYSTEMIC INFLAMMATORY RESPONSE, CARBOHYDRATE AND LIPID METABOLISM IN RATS EXPOSED TO INTRAPERITONEAL AND INTRAGINGIVAL ADMINISTRATION OF SALMONELLA TYPHI LIPOPOLY

The experiment on 70 white rats was designed to investigate the effects of a water-soluble form of quercetin and modulators of AP-1 and Nrf2 transcription factors on the blood indicators of the systemic inflammatory response (SIR), and carbohydrate and lipid metabolism under the conditions of intraperitoneal and intra-gingival administration of S. typhi lipopolysaccharide (LPS). The animals were divided into 7 groups: the 1st group consisted of intact rats; the 2nd group included animals exposed to combined systemic and local administration of LPS - pyrogenal; the 3rd, 4th and 5th groups included the animals who were respectively injected with water-soluble complex of quercetin and polyvinylpyrrolidone (corvitin) in a dose of 100 mg/kg (10 mg/kg in terms of quercetin), an inhibitor of activation of AP-1 SR 11302 (in a dose of 1 mg / kg) and Keap1 / Nrf2 / antioxidant-responsive element (ARE) signaling pathway inducer epigallocatechin-3-gallate (EGCG, in a dose of 21.1 mg / kg) 3 times a week, starting on the 30th day since the experiment modeling. The 6th and 7th groups of the rats were subjected to combined effects of quercetin + SR 11302 and quercetin + EGCG, respectively. The study has demonstrated the combination of quercetin and SR 11302, or EGCG, in systemic and local administration of S. typhi lipopolysaccharide more effectively prevents the production of ceruloplasmin, a SIR marker, by-products of lipid peroxidation in rats’ blood, as well as increases its antioxidant potential compared to the separate application of these drugs. The combination of quercetin and SR 11302, or EGCG, under the experimental conditions has been found out to more effectively correct carbohydrate metabolism disorders (hyperinsulinemia, insulin resistance) than this occurs under separate usage of the agents, but does not reveal significant synergism in the correction of dyslipoproteinemia.

QUERCETIN LIMITS THE DEVELOPMENT OF OXIDATIVE-NITROSATIVE STRESS IN PERIODONTAL TISSUES IN DIFFERENT MODELS SIMULATING SYSTEMIC INFLAMMATORY RESPONSE

The study was carried out to investigate the effect produced by water-soluble form of quercetin (corvitin) on the indices of the development of oxidative-nitrosative stress in periodontal soft tissues of rats subjected to systemic inflammatory response. This condition was simulated by using two models: one was induced by the Salmonella typhi lipopolysaccharide (LPS) administration (in a dose of 0.4 μg / kg of body wt three times through the 1st week and once a week for the next 7 weeks), as well as on the 14th day after a moderate craniocerebral injury (CCI). Applying corvitin in a dose of 500 μg / kg (10 μg / kg recalculated as quercetin) every third day starting from the 30th day of the experiment with the use of pyrogenalum reduced the production of superoxide anion radical (.О) by NADPH-dependent electron transport chains (endoplasmic reticulum and NO-synthase) by 18.1%, but did not considerably affect the mitochondrial chain. .О production by leukocyte NADPH-oxidase was by 16.7% lower. The total NO synthase (NOS) activity in periodontal tissues decreased by 40.6%, and the content of peroxynitrite ions was inferior to the relevant result of the group received pyrogenalum by 13.9%. Administration of corvitin in a dose of 500 mg/kg for 7 days after CCI modeling reduced the (.О) production by NADPH-dependent chains by 20.9%, and by mitochondria by 31.7% on the 14th day of post-traumatic period. .О production by leukocyte NADPH-oxidase was by 35.8% lower. NOS activity in periodontal tissues decreased by 45.8%, the content of peroxynitrite ions was inferior to the relevant value in the group with modeled CCI by 25.7%. This suggests the conclusion that applying water-soluble form of quercetin in conditions of systemic inflammatory response limits the signs of oxidative-nitrosative stress in periodontal soft tissues of rats.

EFFECT OF MODULATORS OF REDOX-SENSITIVE TRANSCRIPTIONAL TRANSCRIPTION FACTORS ON MORPHOLOGICAL CHANGES IN PERIODONTIUM OF RATS DURING SYSTEM INFLAMMATORY RESPONSE

The experiment carried out on 30 white rats was aimed at studying pathomorphological changes in periodontal tissues during lipopolysaccharide-induced systemic inflammatory response and their nature when a water-soluble form of quercetin and epigallocatechin-3-gallate was administered to the animals. The rats were divided into 4 groups: the 1st group included animals after systemic administration of S. typhi lipopolysaccharide (pyrogenal); the 2nd and 3rd group involved animals, which were injected with a water-soluble form of quercetin (10 mg/kg) and epigallocatechin-3-gallate (21.1 mg/kg) intraperitoneally (every 3 days) starting from the 30th day of the experiment. Pyrogenal was administered in a dose of 0.4 μg/kg 3 times during the 1st week and once a week for the next 7 weeks. Sections of 4–6 μm thick were cut from paraffin blocks and stained with hematoxylin and eosin. It has been found out that experimental modeling of a systemic inflammatory response leads to the development of morphological signs of periodontitis, which are manifested by inflammation and destruction of periodontal pockets, the formation of pathological periodontal pockets, destructive changes in bone tissues of the alveolar process and in the cementum of the dental root. The use of the water-soluble form of quercetin and epigallocatechin-3-gallate in the experimental conditions changes the morphological picture of inflammatory and destructive processes in the periodontium: it prevents the formation of purulent exudate, reduces the intensity of the resorption of cementum and bone tissue of the alveolar process, accelerates the development and maturation of granulation tissue in the walls of periodontium, promotes the replacement of bone defects with connective tissue, and enhances the regeneration of cementum.

CO-EFFECT PRODUCED BY WATER-SOLUBLE FORM OF QUERCETIN AND INHIBITOR OF AP-1 TRANSCRIPTION FACTOR ON DISINTEGRATION OF PERIODONTIUM ORGANIC MATRIX IN RATS DURING SYSTEMIC AND LOCAL ADMINISTRATION OF SALMONELLA TYPHI LIPOPOLYSACCHARIDE

The aim of the present study was to investigate the co-effect produced by water-soluble form of quercetin and SR 11302, an inhibitor of AP-1 transcription factor, on biochemical depolymerization markers of periodontal organic matrix during systemic and local administration of S. typhi lipopolisaccharide (LPS). The studies were conducted on 25 white rats of the Wistar line weighing 180-220 g, divided into 5 groups: the 1st group included the intact animals, the 2nd group was made up of the animals subject to the combined systemic and local LPS administration, the 3rd and 4th groups included animals, which were given injections with water-soluble form of quercetin (10 mg / kg) and AP-1 activation inhibitor SR 11302 (1 mg / kg) respectively 3 times a week starting on the 30th day of the systemic LPS administration, and the 5th group involved rats, which were injected with co-administered water-soluble form of quercetin and SR 11302. It has been found out the the quercetin and SR 11302 co-administration during systemic and local LPS administration is accompanied with reduced concentration of free hydroxyproline and N-acetylneuraminic acid (NANA) in the soft and bone tissues of the periodontium compared with the results obtained during the separate administration of these agents. The content of glycosaminoglycans did not change. We can suggest that the co-administration of the water-soluble form of quercetin and SR 11302, the AP-1 activation inhibitor, during systemic and local administration of the S. typhi lipopolysaccharide is a more effective means of correcting disorders of the periodontal connective tissue than when the agents are used separately.

EFFECT OF TRANSCRIPTION FACTOR KAPPA B INHIBITORS ON METABOLIC AND STRUCTURAL DISORDERS IN BONE TISSUE UNDER COMBINED EXCESSIVE INTAKE OF FLUORIDE AND SODIUM NITRATE


 This experiment carried on 40 white Wistar rats aimed at studying the effect produced by inhibitors of the nuclear transcriptional factor kappa B (NF-κB) activation on the mechanisms of metabolic and structural disorders in the femoral bones and vertebrae under combined surplus fluoride and sodium nitrate intake. It has been found out that co-administration of sodium fluoride (10 mg/kg body weight) and sodium nitrate (500 mg/kg of body weight) for 30 days disrupts the autoregulation mechanism of nitrogen monoxide (NO) level in the femoral bones of the test rats that is manifested by an increase in the activity of total NO synthase and its inducible isoform against the background of a decrease in the total arginase activity and the activity of the constitutive NO synthase isoenzymes. Under these conditions, there has been observed the growth in the concentration of free hydroxyproline, N-acetylneuraminic and hexuronic acids in the femoral bones and vertebrae that is indicative of depolymerization of collagen, sialoglycoproteins and proteoglycans, decrease in bone mass, their density, mineral saturation, strength (the Simon index elevated). Inhibitors of NF-κB activation (ammonium pyrolidine dithiocarbamate and a water-soluble form of quercetin) restore the autoregulation mechanism of the NO level in the rats’ femoral bones that is accompanied by a decrease in the total activity of NO synthase, the activity of its inducible isoform, an increase in the total arginase activity and by limited peroxinitrite formation. Ammonium pyrolidine dithiocarbamate and a water-soluble form of quercetin have been shown to result in lowering in the content of free hydroxyproline, N-acetylneuraminic and hexuronic acids in bones that confirms their effectiveness as a means for correcting depolymerization of collagen, sialoglycoproteins and proteoglycans. There has been found their property to promote the growth of bone mass and density of the femurs and vertebrae.

EFFECT OF A WATER-SOLUBLE FORM OF QUERCETIN ON THE DISINTEGRATION OF PERIODONTAL ORGANIC MATRIX IN RATS EXPOSED TO THE SYSTEMIC ADMINISTRATION OF SALMONELLA TYPHI LIPOPOLYSACCHARIDE

The experiment on 30 white rats was designed to investigate the effect of a water-soluble form of quercetin on collagenolysis and depolymerization of proteoglycans and glycoproteins in both soft and bone tissues of periodontium under the conditions of systemic administration of S. typhi lipopolysaccharide. The animals were divided into 3 groups: the 1st group included intact animals, the 2nd group involved the animals exposed to the systemic administration of S. typhi lipopolysaccharide (pyrogenal), the 3rd group was made up the rats, which were given a water-soluble complex of quercetin and polyvinylpyrrolidone (corvitin) intraperitoneally in a dose of 500 mg / kg (10 mg / kg in terms of quercetin) every 3 days, starting from the 30th day of the experiment. The latter was administered in a dose of 0.4 μg/kg 3 times during the 1st week and once a week for the next 7 weeks. Collagenolysis was assessed by the concentration of free hydroxyproline; the level of depolymerisation of proteoglycans and glycoproteins was assessed by the content of glycosaminoglycans (GAGs) and N-acetylneuraminic acid (NANA) respectively. The introduction of quercetin in the experimental conditions significantly reduced the concentration of free hydroxyproline in soft and bone periodontal tissues by 27.3 and 26.7%, GAG – by 36.3 and 39.9%, and NANA – by 17.6 and 46.8%, respectively compared to the values of the 2nd group. The coefficient of root exposure in molars was inferior to the findings in the group with the modelled systemic inflammatory response by 26.9%. It can be concluded that the use of quercetin in the systemic lipopolysaccharide administration significantly reduces the depolymerisation of the components of the organic matrix in soft and bone periodontal tissues (collagen, proteoglycans and sialoglycoproteins), and limits the resorption of the alveolar process in jaws.

Effect Of Quercetin Supplementation On Repeated Sprint Performance And Metabolic Stress

Repeated sprinting has been shown to induce an acute inflammatory response and increase production of reactive oxygen species (ROS) at least partly via activation of the enzyme, xanthine oxidase (XO). In vitro, XO is inhibited by quercetin (Q), a flavonol commonly found in apples, onions and other plant-based foods. PURPOSE: The purpose of the study was to determine the value of quercetin consumption on oxidative stress and inflammation induced by repeated sprint exercise. METHODS: The study was a double-blind, placebo-controlled, cross-over design. Fifteen recreationally active, young adult males with team sport experience completed two repeated sprint tests (RST) each following one week supplementation of either the placebo (P)- a 6% carbohydrate commercial sports drink, or P with 500 mg of isoquercetrin, a glycosylated and water soluble form of quercetin (Q), consumed twice a day (1000 mg/d). The RST consisted of 12x30 m sprints (S1-S12) performed every 35 sec. Sprint times were measured with a dual-beam timing gate system. The performance measure was mean sprint time for the 12 sprints. Blood samples were collected before supplementation (B0), at baseline the morning of each test (B1), immediately post-test (B2), and 1h-post (B3). Blood was analyzed for plasma XO and serum IL-6, IL-1β and uric acid (UA). RESULTS: Mean sprint times increased progressively and were significantly higher by S9 for both treatments (5.9%), however, there were no significant differences between treatments or interactions for the performance measure. Changes in XO, IL-6 and UA from pre-test to post-test were +47%, +77%, and +25% with no difference by treatment. Ninety-two percent of the IL-1β concentrations were undetectable. CONCLUSION: Repeated sprints increased xanthine oxidase activity and inflammation, but this was not attenuated by consumption of quercetin. Supported by a gift from Gatorade Sports Science Institute