Nucleoside-nucleotide Mixture Research Articles

A Mixture of Nucleosides and Nucleotides Increases Bone Marrow Cell and Peripheral Neutrophil Number in Mice Infected with Methicillin-Resistant Staphylococcus aureus

We studied the effects of a mixture of nucleosides and nucleotides on the peripheral neutrophil number and the proliferation of bone marrow cells in mice challenged with methicillin-resistant Staphylococcus aureus. BALB/c mice were fed a nucleotide-free 20% casein diet (control) or this diet supplemented with nucleosides and nucleotides orally (Expt. 1) or intraperitoneally (Expt. 2 and 3). On d 10, the mice were challenged intravenously with methicillin-resistant S. aureus (6.7 × 1012 colony forming units/L). In Expt. 1 and 2, numbers of total and differential counts of blood leucocytes were counted on d 0 (before), 1, 3 and 5 after the infection. In Expt. 3, 30 min before killing, bromodeoxyuridine (20 mg/kg), an analogue of thymidine, was administered intraperitoneally and its incorporation in the DNA synthetic phase of bone marrow cells was determined at 0 h (before), 3, 6 and 24 h after the infection. Mice fed the supplemented diet had higher (P < 0.05) leucocyte and neutrophil numbers on d 0 compared with the control group. The neutrophil numbers tended to be greater in the supplemented group at 1, 3 and 5 d after the infection. Intraperitoneal administration of nucleosides and nucleotides increased (P < 0.05) neutrophil numbers before and after the infection. Twenty-four h after the infection, incorporation of bromodeoxyuridine into the DNA synthetic phase of bone marrow cells in the group administered nucleosides and nucleotides was higher (P < 0.05) than in the control group. We conclude that, following methicillin-resistant S. aureus injection, intraperitoneal administration of a nucleoside-nucleotide mixture may stimulate bone marrow cell proliferation and increase the peripheral blood neutrophil numbers. Oral administration may elicit weaker effects.

A Dietary Nucleoside-Nucleotide Mixture Inhibits Endotoxin-Induced Bacterial Translocation in Mice Fed Protein-Free Diet

Nucleosides and nucleotides are important substrates utilized by the intestinal mucosa. To determine the relative effect of dietary nucleosides and nucleotides on the gut, we investigated the effects of these compounds on endotoxin-induced bacterial translocation, cecal bacterial populations and ileal histology in protein-malnourished mice. There was an inhibition of gram-negative enteric bacteria in the mesenteric lymph node and spleen of the surviving mice fed the protein-free diet supplemented with a nucleoside-nucleotide mixture compared with the nonsupplemented group. Histologically, the damage to the gut mucosal barrier was more pronounced in the nonsupplemented group than in the nucleoside-nucleotide supplemented group. However, the cecal bacterial populations in the groups were not different. The villous height, crypt depth and total wall thickness were more developed in the supplemented group compared with the nonsupplemented group, indicating that the nucleoside-nucleotide mixture blocked bacterial translocation by preventing endotoxin-induced mucosal or epithelial damage. These results suggest that the nucleoside-nucleotide mixture could be used to inhibit or reduce the incidence of bacterial translocation, decrease intestinal injury and improve survival in a lethal model of protein deficiency and endotoxemia.

Supplementation of Nucleoside-Nucleotide Mixture Enhances Functional Recovery and Energy Metabolism Following Long-Time Hypothermic Heart Preservation

OG-VI, a well-balanced mixture of nucleoside and nucleotides, has been demonstrated to have a favorable effect on energy metabolism. In this study, we tested the hypothesis that addition of OG-VI to the University of Wisconsin solution can improve the cardiac functional recovery following long-time hypothermic preservation. Forty-two male Wistar rats were randomized into four groups. After 30-min of isolated working heart perfusion, the rat hearts were arrested with St. Thomas cardioplegic solution and preserved at 4 degrees C in saline, OG-VI, UW, and UW+OG-VI, respectively. After 12-h of preservation, the hearts were reperfused for 60-min during which the recovery of cardiac functions were monitored continuously. Myocardial adenine nucleotides were analyzed using high-performance liquid chromomatograph. In the UW+OG-VI group, the recovery of cardiac output, coronary flow, aortic flow, rate-pressure product, left ventricle stroke volume, and stroke work were significantly higher than other groups (P < 0.05). Furthermore, all phosphate high-energy compounds were significantly higher in the UW+OG-VI group than in the other groups (P < 0.05). Coronary vascular resistance and myocardial wet/dry weight ratio were obviously lower in the UW+OG-VI group, compared to the other groups (P < 0.05). Heart function was better recovered when nucleoside-nucleotide mixture was added to UW solution during long-time hypothermic rat heart preservation. The mechanism is not totally clear, but enhancement of high-energy phosphate production is possible.

Nutrition beyond nutrition: plausibility of immunotrophic nutrition for space travel

Background and aims: Microgravity has adverse effects on the immune system. We examined the effects of supplemental dietary nucleotides on immune function in ground-based in vivo anti-orthostatic tail-suspended (AOS) mice and in vitro (bioreactor—BIO) analogs of microgravity. Methods: BALB/c mice were divided into the following three groups: group housed, single isolation, and AOS. Mice were fed either control chow or chow supplemented with RNA or uracil. Immune function was assessed by in vivo popliteal lymph node proliferation (PLN), in vitro PHA-stimulated proliferation of splenocytes and cytokine production. BIO splenocytes were cultured in vitro with/without PHA, a nucleoside-nucleotide mixture (NS/NT) or uridine. The cell proliferation and scanning electron microscopic examination for cells were carried out.Results: PLN response was significantly suppressed in AOS mice (P<0.05) and was restored by RNA and uracil diets. Splenocytes from AOS mice had decreased phytohemagglutinin (PHA)-stimulated proliferation, decreased IL-2 and IFN-γ cytokine levels (P<0.05). These responses were restored by RNA and uracil diets. In BIO cultures, PHA response was suppressed significantly, and uridine and NS/NT restored the proliferative responses. Scanning electron microscopic analysis of cells cultured in BIO revealed cells with pinched, distorted and eroded membranes. Nucleotide supplementation especially uridine restored normal activated cell surface appearance and ruffling. Conclusion: In the microgravity analog environment of AOS and BIO, supplemental nucleotides and especially uracil/uridine have up-regulating and immunoprotective effects with potential as a countermeasure to the observed immune dysfunction in true microgravity.

A Nucleoside-Nucleotide Mixture May Reduce Memory Deterioration in Old Senescence-Accelerated Mice

We investigated the effects of a mixture of dietary nucleosides and nucleotides (NS + NT) on memory in 1- and 7-mo-old senescence-accelerated mice (SAM). Memory retention was studied with passive avoidance (step-through) and active avoidance (shuttle) tests. For 14 wk, mice in the control groups were fed a 20 g of casein/100 g diet, whereas the NS + NT groups were fed this diet supplemented with a 0.5 g of NS + NT mixture/100 g. All mice were killed at wk 14, and we studied the brain histopathology. Lipofuscin, monovacuoles and multiple vacuoles of various brain regions were measured. Body weight, food intake and ambulatory activity did not differ between the control and NS + NT groups. In old mice, the time of passive avoidance was significantly higher in the NS + NT group than in the control group at d 1 and 7 (P: < 0.05). However, such an effect of NS + NT was not observed in young mice. In the active avoidance test, the incidence of successful avoidance in old mice was higher in the NS + NT group than in the control group at d 1 and 2 (P: < 0.05). The percentages of specific brain cells containing lipofuscin were lower in NS + NT groups than in the control groups in both young and old mice (P: < 0.05). The number of monovacuoles and multiple vacuoles in specific brain regions tended to be lower (P: = 0.1-0.25) in NS + NT than in control groups, with significant differences in the microvacuoles of the middle cortex of young mice and in the multiple vacuoles in the hind cortex of old mice (P: < 0. 05). These results suggest that increased dietary NS + NT may be associated with decreases in the age-induced deterioration of brain morphology and certain memory tasks.

Effects of pimobendan and EGIS 9377, cardiotonic agents, and OG-VI, a nucleoside-nucleotide mixture, administered during reperfusion after ischemia on stunned myocardium in dogs.

Pimobendan is a so-called calcium sensitizer that exerts a positive inotropic action. EGIS 9377 is synthesized as a calcium sensitizer. OG-VI is a nucleoside-nucleotide mixture that ameliorates the myocardial dysfunction (myocardial stunning) after ischemia. To determine whether administration of these agents after the onset of reperfusion after ischemia improves the condition of stunned myocardium. Dogs anesthetized with pentobarbital were subjected to 20 min ligation of left anterior descending coronary artery and then 60 min reperfusion. The corresponding vehicle, 0.3 and 1 mg/kg pimobendan, or 1 and 3 mg/kg EGIS 9377 was injected intravenously 30 min after the onset of reperfusion. Saline solution or 1.2 mumol/kg per min OG-VI was infused for 30 min, starting 30 min after the reperfusion. Shortening of myocardial segment was measured by sonomicrometry. The tissue levels of energy and carbohydrate metabolites in the 60 min-reperfused hearts were determined. Shortening of myocardial segments significantly decreased during ischemia, and returned toward preischemic level after reperfusion for all groups, although the contractile dysfunction still remained. Injections and infusion of pimobendan, EGIS 9377, and OG-VI after the onset of reperfusion ameliorated the contractile dysfunction. Systemic vascular resistance was decreased by administrations of pimobendan and OG-VI. The levels of high-energy phosphates in 60 min-reperfused heart were not changed by either treatment. Administration of pimobendan, EGIS 9377, and OG-VI ameliorate the myocardial contractile dysfunction after ischemia even when these agents are administered after the onset of reperfusion. The increase in contractile function due to these agents did not worsen the myocardial energy balance.

Nucleoside-nucleotide mixture increases bone marrow cell number and small intestinal RNA content in protein-deficient mice after an acute bacterial infection.

The aim of this study was to determine if intraperitoneal administration of a nucleoside-nucleotide mixture would affect small intestinal morphology, bone marrow cell number, and DNA content in protein-deficient mice subjected to acute bacterial infection. Mice were randomized into two groups and orally fed protein-free diet or nucleotide-free 20% casein diet for 10 d. The mice in each group were divided into two subgroups and intraperitoneally administered 0.35 mL saline or nucleoside-nucleotide mixture (17.5 mL/kg body weight) for 10 d. On day 10, one subgroup from each major dietary group was either inoculated intravenously with methicillin-resistant Staphylococcus aureus or saline. Three days later, small intestinal morphology, bone marrow cell number, and DNA content were evaluated in infected and noninfected mice. Protein-deficiency in association with infection significantly (P < 0.05) reduced body weight, small intestinal weight, crypt depth, villous height, and wall thickness. All dietary groups exhibited similar small intestinal DNA and protein contents (protein:DNA ratio, RNA:DNA ratio) at 3 d postinfection. However, small intestinal RNA content in the infected protein-free dietary group administered nucleoside-nucleotide mixture was higher (P < 0.05) and tended to be higher relative to the infected nucleotide-free 20% casein group administered nucleoside-nucleotide mixture compared with the rest of the groups. In the infected protein-free dietary group administered nucleoside-nucleotide mixture, bone marrow cell number and bone marrow DNA content were higher (P < 0.05) relative to the infected protein-free dietary group, nucleotide-free 20% casein diet administered saline, or nucleoside-nucleotide mixture, respectively. We conclude that intraperitoneal administration of nucleoside-nucleotide mixture may stimulate bone marrow cell proliferation, DNA content, and small intestinal RNA content during periods of relative deficiency such as protein-deficiency in combination with infection.

Dietary nucleoside-nucleotide mixture aggravates nasal allergic responses induced by toluene diisocyanate in mice

In this study we evaluated the effect of a dietary nucleoside-nucleotide mixture (NNM) on nasal allergy induced by toluene diisocyanate(TDI) in mice. Female ddY mice were randomized into two groups and fed a nucleic-acid free 20% casein (control) or this diet supplemented with NNM for 4 weeks. On the 4th week, mice were divided into 2 sub-groups; NNM sensitized, NNM- nonsensitized, control-sensitized and control-nonsensitized. The sensitized groups of mice were treated with two courses of intranasal application of 5% TDI in diethyl acetate for 5 consecutive days each time, separated by one week rest. Nonsensitized group of mice were similarly treated with vehicle. A week after the second sensitization all the treatment groups were provoked by applying 2.5% of TDI in vehicle. Nasal responses of sneezing, rhinorrhea, itching and snort at provocation, were scored for ten minutes. Degree of hair loss from the snout of mice was also scored for the length of the experiment. Lung and serum IgE were measured by ELISA. Results show that the sensitized groups of mice from each dietary group sneezed more frequently than the nonsensitized groups (p< 0.05). The NNM sensitized group sneezed more frequently that was different (p< 0.05) compared to the rest of the groups. Nasal responses for the sensitized groups were higher relative to the nonsensitized groups, with the NNM sensitized group having an overall higher nasal response than the rest of the groups. Both sensitized group of mice showed a higher concentration of lung and serum IgE compared to the non-sensitized groups (p<0.05, with the NNM sensitized group having an overall higher IgE concentrations in both tissues compared to the rest of the groups (p< 0.05). We conclude that dietary NNM may aggravate nasal allergic responses in the predisposed.

Nucleoside-nucleotide-free diet suppresses cytokine production and contact sensitivity responses in rats with trinitrobenzene sulphonic acid-induced colitis.

We examined the effects of dietary nucleoside-nucleotide mixture on synthesis of inflammatory cytokines, interleukin-8 and tumor necrosis factor-alpha, in sensitized and nonsensitized colitic rats. Sensitized and nonsensitized colitic rats that were fed a nucleoside-nucleotide mixture had greater colonic weight and macroscopic and microscopic damage scores than nucleoside-nucleotide-free sensitized and nonsensitized colitic rats. Increased colonic tumor necrosis factor-alpha and interleukin-8 concentrations were associated with increased colonic inflammation and ulceration in the nucleoside-nucleotide mixture-fed group. There was also increased ear thickness in the nucleoside-nucleotide mixture-fed sensitized and nonsensitized colitic rats, which correlated highly with increased tumor necrosis factor-alpha and interleukin-8 levels in the ear lobes. Nucleoside-nucleotide-free diets may suppress cytokine secretion, thereby reducing colonic damage and contact sensitivity responses in colitic rats.

Nucleoside-Nucleotide-Free Diet Suppresses Cytokine Production and Contact Sensitivity Responses in Rats With Trinitrobenzene Sulphonic Acid-Induced Colitis

AbstractWe examined the effects of dietary nucleoside-nucleotide mixture on synthesis of inflammatory cytokines, interleukin-8 and tumor necrosis factor-a, in sensitized and nonsensitized colitic rats. Sensitized and nonsensitized colitic rats that were fed a nucleosidenucleotide mixture had greater colonic weight and macroscopic and microscopic damage scores than nucleoside-nucleotide-free sensitized and nonsensitized colitic rats. Increased colonic tumor necrosis factor-a and interleukin- 8 concentrations were associated with increased colonic inflammation and ulceration in the nucleoside-nucleotide mixture-fed group. There was also increased ear thickness in the nucleoside-nucleotide mixture-fed sensitized and nonsensitized colitic rats, which correlated highly with increased tumor necrosis factor-a and interleukin-8 levels in the ear lobes. Nucleoside-nucleotide-free diets may suppress cytokine secretion, thereby reducing colonic damage and contact sensitivity responses in colitic rats.

The well-balanced nucleoside-nucleotide mixture ?OG-VI? for special medical purposes

The well-balanced nucleoside-nucleotide mixture ?OG-VI? for special medical purposes

Effects of OG-VI, a nucleoside-nucleotide mixture, on ischemic myocardial metabolism in dogs.

OG-VI is a solution composed of 30 mmol/l inosine, 30 mmol/l sodium 5'-guanylate, 30 mmol/l cytidine, 22.5 mmol/l uridine, and 7.5 mmol/l thymidine, which is known to improve myocardial stunning. To study the effect of OG-VI on myocardial energy and carbohydrate metabolism during ischemia. Ischemia was induced in pentobarbital-anesthetized open-chested dogs for 3 min by left anterior descending coronary artery ligation. Saline, 1.2 mmol/kg per min OG-VI, or 12 mmol/kg per min OG-VI was infused at 0.1 ml/kg per min, starting 30 min before the onset of ischemia. The myocardium was extracted 3 min after the onset of ischemia, and used to determine the tissue levels of energy and carbohydrate metabolites. Ischemia decreased the levels of ATP and fructose 1,6 diphosphate significantly, and increased those of AMP, glucose 6 phosphate, fructose 6 phosphate and lactate. OG-VI infusion preserved the adenine nucleotide levels significantly in 3 min ischemic hearts, and attenuated the ischemia-induced alteration of carbohydrate metabolism. OG-VI may improve the myocardial metabolic derangement induced by ischemia.

Nucleoside-nucleotide free diet protects rat colonic mucosa from damage induced by trinitrobenzene sulphonic acid.

Growing evidence suggests that intestinal recovery from injury induced by radiation, endotoxin, and protein deficiency is improved by the ingestion of nucleosides and nucleotides. This study examined the effect of dietary nucleosides and nucleotides supplementation on trinitrobenzene sulphonic acid induced colonic damage in experimental colitis. Sprague-Dawley rats were randomised into two groups and fed nucleic acid free 20% casein diet (control) or this diet supplemented with 0.5% nucleoside-nucleotide mixture for four weeks. On the second week, colonic inflammation was induced in rats by intracolonic administration of 0.25 ml of 50% ethanol containing 25 mg of trinitrobenzene sulphonic acid. Additionally, other sets of rats were treated with 0.25 ml of 50% ethanol, 25 mg of trinitrobenzene sulphonic acid in 0.25 ml saline, or 0.25 ml of 0.9% saline. After two weeks, colon weight, macroscopic and microscopic damage scores, were significantly greater (p < 0.05) in the nucleoside-nucleotide supplemented group compared with the non-supplemented control groups. The same variables seen in the trinitrobenzene sulphonic acid-ethanol group fed nucleoside-nucleotide free diet were greater (p < 0.05) than in the rest of the groups fed nucleoside-nucleotide free diet and treated with ethanol, trinitrobenzene sulphonic acid in saline, or saline. Histologically, segmental ulceration and inflammation associated with significantly increased infiltration of polymorphonuclear leucocytes, macrophages, lymphocytes, fibroblasts were observed in the supplemented group compared with the controls. In the nucleoside-nucleotide supplemented group the epithelial damage, mucosal erosion, oedema, and coagulative necrosis of the muscularis propria was more extensive in comparison to the non-supplemented control groups. This study suggests that dietary nucleosides and nucleotides may aggravate colonic damage and inflammation in chemically induced experimental colitis in rats; and that nucleoside-nucleotide free diet combined with other pharmacological agents may offer a better response.

A Nucleoside-Nucleotide Mixture and Its Components Increase Lymphoproliferative and Delayed Hypersensitivity Responses in Mice

We studied the effect of individual components of a nucleoside-nucleotide mixture on T cell-mediated immunity in BALB/c and DBA/2 mice. Mice were fed for 4 wk a nucleotide-free 20% casein diet (control) or this diet supplemented with 3 mol/kg of one of the following; inosine, guanosine monophosphate, uridine, cytidine, thymidine, or a mixture of these. In both strains of mice, popliteal lymph node immunoproliferative response to alloantigeneic (C57BL/6 splenic cells) challenge in mice fed the mixture and guanosine monophosphate was greater (P < 0.05) than in the mice fed the control diet. BALB/c mice fed inosine, uridine, and thymidine also showed greater (P < 0.05) responses compared with control fed mice. In the sheep red blood cells challenge assay, foot pad weight-gain in both strains of mice fed the mixture and the individual components supplemented diets was greater (P < 0.05) than in those fed the control diet. In both strains of mice, interleukin-2 secretion by popliteal lymph node lymphocytes in mice fed the mixture and thymidine was higher (P < 0.05) compared with the rest of the groups except BALB/c mice fed cytidine. Significantly higher than control secretions of interferon-γ were observed only in BALB/c mice fed inosine, thymidine and the mixture. We conclude that mice fed the nucleoside-nucleotide mixture and the individual components of the mixture had greater responses in the T cell-mediated immune functions studied and that the responses in mice fed the mixture were not different from those in mice fed the individual components.

Effect of a parenteral nucleoside-nucleotide mixture on hepatic metabolism in partially hepatectomized cirrhotic rats

After hepatectomy, purine and pyrimidine metabolism is a key process in synthesis of DNA and RNA and in energy metabolism. To supply nucleosides for salvage synthesis, nucleoside-nucleotide mixture solutions have been developed, and they have been found to improve protein metabolism and hepatic regeneration after partial hepatectomy in normal rats. However, the effect of the solution in cirrhotic liver, common in patients with hepatocellular carcinoma, has not been reported. The aim of this study was to evaluate the metabolic effect of the nucleoside-nucleotide mixture on cirrhotic rats after partial hepatectomy. Seventy percent partial hepatectomy was performed in thioacetamide-administered cirrhotic rats. The fractional protein synthetic rate, nitrogen balance, hepatic content of nucleic acid, and blood chemistry after the administration of the nucleoside-nucleotide mixture solution (OG-VI) with total parenteral nutrition was evaluated at 7 d after partial hepatectomy. OG-VI increased hepatic RNA level and hepatic fractional protein synthetic rate ( p < 0.05). It is concluded that the nucleoside-nucleotide mixture solution is an effective nutritional supplement to the metabolism of cirrhotic rats after partial hepatectomy.

Comparative effects of dietary nucleoside-nucleotide mixture and its components on endotoxin induced bacterial translocation and small intestinal injury in protein deficient mice.

Nucleoside-nucleotide mixture has been shown to improve gut morphology and reduce the incidence of bacterial translocation in protein deficient mice. To compare the reparative effect of nucleoside-nucleotide mixture and their individual components on maintenance of gut integrity and bacterial translocation based on their differential metabolism and utilisation. ICR (CD-1) mice were randomised into eight groups of 10 animals each and fed 20% casein diet (control), protein free diet, or protein free diet supplemented with 3 M cytidine, uridine, thymidine, inosine, guanosine monophosphate, or nucleoside-nucleotide mixture for four weeks. On the fourth week, each mouse was injected lipopolysaccharide intraperitoneally (50 micrograms/500 microliters) and the incidence of bacterial translocation, caecal bacterial populations, and the ileal histology, noted 48 hours later. The death rate in the control group was 40% compared with 10% in the nucleoside-nucleotide mixture and 20% each in the individual components groups, respectively. Bacterial translocation to the mesenteric lymph node did occur in 100% of the surviving mice fed the control diet in comparison with 44% (nucleoside-nucleotide), 50% (cytidine), 75% (thymidine), 75% (uridine), 63% (inosine), and 63% (guanosine monophosphate). Histologically, the damage to the gut was more distinct in the protein free diet group. Villous height, crypt depth, and wall thickness in the nucleoside-nucleotide mixture group mean (SEM) (5.01 (0.34); 0.87 (0.14); 0.33 (0.10)), were respectively, higher compared with the protein free diet (3.34 (0.34); 0.61 (0.03); 0.18 (0.04)) group. In the cytidine group, crypt depth (0.86) (0.08)), and wall thickness (0.30 (0.002)) were higher. The same measurements in the components groups tended to be higher than the protein free diet group. Caecal bacterial populations were, however, similar in all groups. These results suggest that dietary nucleosides and nucleotides are essential nutrients for intestinal repair; nucleotides or cytidine provide a better response.

Efficacy of nucleoside-nucleotide mixture against methicillin-resistant Staphylococcus aureus infection in mice treated with cyclophosphamide

The effects of nucleoside-nucleotide mixture (NNM) and granulocyte-colony stimulating factor (G-CSF) on response to methicillin-resistant Staphylococcus aureus (MRSA) challenge in cyclophosphamide (CPA) treated mice were studied. Thirty BALB/c mice were randomly divided into 3 groups of 10 animals each and fed 20% nucleotide-free casein diet. On the 10th day on the diet, mice were intraperitoneally administered CPA and 4 hr later, inoculated intravenously with viable MRSA organisms. The mice were intraperitoneally administered saline (control group) or NNM daily from the onset of the experiment or injected G-CSF for 4 consecutive days beginning on the day after CPA injection. The cumulative percentage of survival over 10 days in the control group was 20% as compared to 60% and 80% in the NNM and G-CSF groups, respectively. Of the surviving mice, in the NNM group about half eliminated the MRSA organisms in spleen and kidney, as compared to none in the control and G-CSF groups. Our results suggest that administration of NNM as well as G-CSF may be used to an advantage to enhance the host resistance in CPA treated septic mice; and that NNM alone or in combination with other nutrients or pharmacologic agents may prove to be of clinical importance in the protection of immunocompromised patients against opportunistic pathogens.

Comparative Effects of Orally and Intraperitoneally Administered RNA and Nucleic Acid Components on Response to Methicillin-ResistantStaphylococcus aureusInfection in Mice

Abstract The effects of the routes of administration of RNA and nucleoside-nucleotide mixture on the survival of BALB/c mice following challenge with methicillin-resistant Staphylococcus aureus (MRSA) organisms were examined. The mice were randomized into 5 groups: Group A (n = 19) fed nucleic acid-free 20% casein diet (NFD) (control); Group B (n = 20) fed NFD supplemented with 0.5% RNA; Group C (n = 10) fed NFD and intraperitoneally administered 0.35ml of 4.22% (W/V) RNA; Group D (n = 15) fed NFD and supplemented with 0.5% nucleoside-nucleotide mixture; and Group E (n = 15) fed NFD and intraperitoneally administered 0.35ml of 3.35% (W/V) nucleoside-nucleotide mixture. The mice in Groups A, B, and D were intraperitoneally administered 0.35ml saline. All the mice in the various groups were maintained on these treatments for 30 days. On day 10, each mouse was challenged with 2.0 × 108 colony forming units (cfu) of MRSA administered intravenously. The survival rates in the orally administered groups were 35%...

Intraperitoneal administration of nucleoside-nucleotide mixture inhibits endotoxin-induced bacterial translocation in protein-deficient mice.

Nucleosides and nucleotides as a precursor for nucleic acid synthesis may be essential for rapidly growing cells, since intestinal epithelial cells have limited capacity for the de novo purine and pyrimidine synthesis. The present study was undertaken to determine the effect of intraperitoneal administration of nucleoside-nucleotide mixture (NNM) or saline on endotoxin-induced bacterial translocation, ileal histology, and cecal population levels in protein-deficient mice. Intraperitoneal administration of NNM for 14 days was associated with reduced translocation of gram-negative enterics to the mesenteric lymph node and spleen in comparison to saline. Histologically, the extent of the damage to the gut mucosa was greater in the saline group. This was confirmed by the profound diminution of the villous height, crypt depth, and the intestinal wall in the saline treated group as compared to the NNM treated group, suggestive of the efficacy of NNM in improving the gut and epithelial mucosal cells. However, the cecal population levels in both groups were not different. Additionally, the mice in the saline group were more susceptible to the lethal effects of endotoxin as compared to the NNM group suggesting that NNM may be essential for the enhancement of the host defense system. These results suggest that NNM may be used to an advantage to inhibit or reduce the incidence of endotoxin-induced bacterial translocation and improved survival in protein-deficient mice.

The effects of oral RNA and intraperitoneal nucleoside-nucleotide administration on methicillin-resistant Staphylococcus aureus infection in mice.

The effects of oral RNA and intraperitoneal nucleoside-nucleotide mixture administration on methicillin-resistant Staphylococcus aureus (MRSA) strain 8985N infection were studied in mice. BALB/c mice were fed a nucleic acid-free diet or nucleic acid-free diet supplemented with 0.5% or 2.5% ribonucleic acid (RNA) for 30 days. Nucleoside-nucleotide mixture or saline (control) was intraperitoneally administered daily to these rats except for the 2.5% RNA group, which received saline only. On the 10th day of this treatment, the mice were inoculated intravenously with the viable MRSA organisms. Susceptibility to the MRSA was determined by animal survival and recovery of the MRSA from the organs. The survival rates in the three groups that were administered saline were 29%, 35%, and 40% for nucleic acid-free diet, 0.5% RNA, and 2.5% RNA groups, respectively, whereas in the two groups that received the nucleoside-nucleotide mixture the rates were 69% for the nucleic acid-free diet group and 55% for 0.5% RNA group. The susceptibility of the mice to the MRSA challenge was not affected by dietary RNA, which indicates the ineffectiveness of oral RNA. The combined survival rate in the two nucleoside-nucleotide groups (64%) was statistically different (p < .01) from that in the three saline groups (34%). There was a greater reduction in viable organism recovery in the kidney and spleen of the surviving mice that had been administered the nucleoside-nucleotide mixture than in those administered saline.(ABSTRACT TRUNCATED AT 250 WORDS)