Reduction In Urinary Excretion Research Articles

Evaluation of selected protein biomarkers of renal function in rats with an experimental model of acute cyclophosphamide-induced cystitis treated with N-acetylcysteine.

The administration of cyclophosphamide (CP) is associated with the risk of developing cystitis as well as kidney injury. The aim of the study was to verify the uroprotective effect of N-acetylcysteine (NAC), as well as the evaluation of renal function in the experimental model of acute CP-induced cystitis. Rats from group 1 received intraperitoneally only a single dose of 200 mg/kg b.w. of CP. Individuals from groups 2 and 3 additionally received a single dose of 200 mg/kg b.w. of NAC, respectively, orally (p.o.) and intraperitoneally (i.p.). After the administration of the drugs, animals were subject to individual monitoring in metabolic cages to assess 24-hour diuresis and basic vital signs, and then finally sacrificed for the purpose of collecting blood and organs for histopathological analysis. Classic renal parameters (creatinine, urea, uric acid, electrolytes) as well as new markers reflecting renal function, within the filtration-resorption range - cystatin C (CysC), renal tubular integrity - kidney injury molecule-1 (KIM-1) and the condition of the glomerular filtration barrier (nephrin) were determined in the obtained serum and urine samples. In group 1 histopathological development of cystitis was confirmed with the absence of significant pathomorphological disorders of the kidneys, and the initial results of the parameters determined were obtained. In both groups 2 and 3, a decrease of inflammatory changes in urinary bladder was observed, while there were still no morphological disturbances in kidneys. The administration of NAC in both groups 2 and 3 also resulted in a decrease of concentrations in urine and a reduction in 24-hour excretion with urine of all assessed proteins (CysC, KIM-1 and nephrin). NAC, thus exhibited a uroprotective effect, which was accompanied by a functional nephroprotective effect (more accentuated during intraperitoneal administration of this compound), manifested by the reduction of urinary excretion of proteins indicative of developing renal dysfunction.

Organic diet intervention significantly reduces urinary pesticide levels in U.S. children and adults

BackgroundPrevious diet intervention studies indicate that an organic diet can reduce urinary pesticide metabolite excretion; however, they have largely focused on organophosphate (OP) pesticides. Knowledge gaps exist regarding the impact of an organic diet on exposure to other pesticides, including pyrethroids and neonicotinoids, which are increasing in use in the United States and globally. ObjectiveTo investigate the impact of an organic diet intervention on levels of insecticides, herbicides, and fungicides or their metabolites in urine collected from adults and children. MethodsWe collected urine samples from four racially and geographically diverse families in the United States before and after an organic diet intervention (n = 16 participants and a total of 158 urine samples). ResultsWe observed significant reductions in urinary levels of thirteen pesticide metabolites and parent compounds representing OP, neonicotinoid, and pyrethroid insecticides and the herbicide 2,4-D following the introduction of an organic diet. The greatest reductions were observed for clothianidin (− 82.7%; 95% confidence interval [95% CI]: − 86.6%, − 77.6%; p < 0.01), malathion dicarboxylic acid (MDA), a metabolite of malathion (− 95.0%; 95% CI: − 97.0%, − 91.8%; p < 0.01), and 3,5,6-trichlor-2-pyridinol (TCPy), a metabolite of chlorpyrifos (− 60.7%; 95% CI: − 69.6%, − 49.2%; p < 0.01). Metabolites or parent compounds of the fungicides boscalid, iprodione, and thiabendazole and the neonicotinoid insecticide imidacloprid were not detected among participants in our study. ConclusionAn organic diet was associated with significant reductions in urinary excretion of several pesticide metabolites and parent compounds. This study adds to a growing body of literature indicating that an organic diet may reduce exposure to a range of pesticides in children and adults. Additional research is needed to evaluate dietary exposure to neonicotinoids, which are now the most widely used class of insecticides in the world.

Gut micro flora in genesis of methilthyo metabolites of paracetamol

Gut micro flora represents a system of extensive metabolic capacity which is quite different when compared to other cells of body and organs. In recent times, there has been an evidence of very important role of gut cysteine conjugate beta-lyases in metabolism of cystein conjugates. A lot of studies are dedicated to exploration of the role of gut micro flora in formation of methylthio adducts from paracetamol in conventional mice and those treated with neomycin as our study. A highly significant reduction in urinary excretion of 3-methylthioparacetamol in group of neomycin-treated mice was confirmed as well its glucuronic acid and sulphate conjugates. Following the principal role of gut flora in the C-S cleavage of paracetamol l-3-cyctein it is clear that highest concentration of methylthio adducts from paracetamol are presented in pretreated mice.

ВПЛИВ ВОДИ ВІД’ЄМНОГО ОКИСНО-ВІДНОВНОГО ПОТЕНЦІАЛУ НА ФУНКЦІЮ НИРОК В ОЛІГУРИЧНІЙ СТАДІЇ СУЛЕМОВОЇ НЕФРОПАТІЇ

Відомо, що зниження окисно-відновного потенціалу води на кожні 59 мВ призводить до збільшення кількості електронів у 10 разів.Мета дослідження – з’ясувати вплив навантаження водою від’ємного окисно-відновного потенціалу на показники функції нирок, порівняно з індукованим діурезом звичайною водогінною водою в олігуричній стадії сулемової нефропатії.Матеріали і методи. У дослідах на 40 білих нелінійних статевозрілих щурах-самцях в олігуричній стадії сулемової нефропатії, яку моделювали за умов гіпонатрієвого раціону харчування шляхом підшкірного введення сулеми в дозі 5мг/кг, при навантаженні водою від’ємного окисно-відновного потенціалу (-232,0±25,12) мВ, порівняно з індукованим діурезом звичайною водогінною водою (окисно-відновний потенціал (88,7±18,35) мВ, який вимірювали ОВП-метром, досліджено екскреторну, іонорегулювальну та кислоторегулювальну функції нирок.Результати досліджень та їх обговорення. За умов досліду встановлено гальмування діурезу та відносного діурезу, що поліпшенням покращанням реабсорбції іонів натрію в проксимальних і дистальних канальцях за рахунок збільшення постачання електронів до канальців нирок. Зазначене положення підтверджено за допомогою багатофакторного регресійного аналізу, оскільки тенденції до наростання дистальної та проксимальної реабсорбції іонів натрію призвели до зменшення синдрому втрати іонів натрію з сечею із тенденцією наростання його концентрації в плазмі крові та встановленням достовірних корелятивних зв’язків (р&lt;0,05) між вищезазначеними показниками. Покращання енергетичного стану проксимального відділу нефрона за умов досліду призвело до поліпшення реабсорбції білка та зменшення його екскреції з сечею. У результаті зазначених змін відбулося зниження постачання іонів натрію до macula densa дистального відділу нефрона, гальмування тубуло-гломерулярного зворотного зв’язку із зниженням реактивності ренін-ангіотензин-альдостеронової системи та зменшенням концентрації і екскреції іонів калію із сечею. Зниження екскреції аміаку зумовлені олужнювальними властивостями мікрогідрину, що викликало гальмування амоніогенезу, який зазвичай активується при некомпенсованих ацидозах.

Consumption of 5-hydroxymethylfurfural-rich dried fruits is associated with reduction in urinary excretion of 8-hydroxy-2′-deoxyguanosine: a randomized clinical trial

5-Hydroxymethylfurfural is widely presented in foods and produced through the degradation of hexoses and the Maillard reaction. This study aimed to investigate any association between 5-HMF content of consumed dried fruits and urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG). The study consisted of 75 healthy volunteers. After an overnight fasting, two urine samples were collected before and 5 h after consumption of date, apricot, currant, plum and fruit bread, 100 g each. Twenty-five samples from frequently consumed types of dried fruits were analyzed for 5-HMF with HPLC. Urinary 5-hydroxymethyl-2-furoic acid (HMFA) and 8-OHdG were determined using HPLC and ELISA, respectively. The amount of 5-HMF in the tested samples varied from 314.8 ± 166.1 to 2496.3 ± 2301.2 mg/kg. The lowest and highest levels of 8-OHdG were 10.1 ± 1.5 µg/g creatinine for plum and 24.7 ± 6.6 µg/g creatinine for date. At the two time points, mean HMFA levels varied from 630.6 ± 114.5 to 2116.8 ± 600.3 and 286.7 ± 24.8 to 582.0 ± 119.2 (µg/g creatinine), respectively. There was a significant difference in HMFA amounts of the samples before and after consumption of apricot and plum (P 0.66, P < 0.01). It is concluded that consumption of 5-HMF-rich dried fruits is associated with a significant reduction in urinary excretion of 8-OHdG.

Variation in hydration status within the normative range is associated with urinary biomarkers of systemic oxidative stress in Guatemalan preschool children

Researchers have increasingly sought noninvasive methods to determine health and nutritional status in humans. Easy and painless to collect, human urine is a source of noninvasive biomarkers. We aimed to explore the relation between systemic oxidative stress biomarkers excreted in urine and urinary osmolality (Uosm). The current trial was a descriptive, cross-sectional study. We collected seventy-eight samples of 24-h urine in preschoolers who were attending daycare centers in the Western Highlands province of Quetzaltenango, Guatemala. After we measured the total urine volume (Uvol), the aliquot was stored for the later determination of Uosm as a hydration biomarker and to measure 15-isoprostane F2t (F2-Iso) and 8-hydroxydeoxyguanosine (8-OHdG) as biomarkers of cellular oxidation with the use of ELISA assay kits in Spain. Descriptive statistics and linear [Spearman rank-order (rs)] and nonlinear (goodness-of-fit) correlations were performed. Twenty-four hour Uvols ranged from 65 to 1670 mL, whereas the Uosm varied between 115 and 1102 mOsm/kg. With respect to oxidative biomarkers, the 24-h urinary output of F2-Iso and 8-OHdG had median values of 748 and 2793 ng/d, respectively. The Uvol correlated inversely and significantly with the concentrations of both oxidative biomarkers (F2-Iso rs = -0.603, P < 0.001; 8-OHdG rs = -0.433, P < 0.001), whereas the Uosm was correlated in a direct manner (F2-Iso rs = 0.541, P < 0.001; 8-OHdG rs = 0.782, P < 0.001) when analyzed as a concentration. Associations were weaker when they were analyzed as the total 24-h production. Preschool children from the Western Highlands of Guatemala show strong correlations between hydration status measured through the use of Uosm and biomarkers of oxidative stress in urine. Thus, a relatively superior hydration status is associated with a quantitative reduction in urinary excretion of systemic oxidation products. This trial was registered at clinicaltrials.gov as NCT02203890.

Red wine and component flavonoids inhibit UGT2B17 in vitro

BackgroundThe metabolism and excretion of the anabolic steroid testosterone occurs by glucuronidation to the conjugate testosterone glucuronide which is then excreted in urine. Alterations in UGT glucuronidation enzyme activity could alter the rate of testosterone excretion and thus its bioavailability. The aim of this study is to investigate if red wine, a common dietary substance, has an inhibitory effect on UGT2B17.MethodsTestosterone glucuronidation was assayed using human UGT2B17 supersomes with quantification of unglucuronidated testosterone over time using HPLC with DAD detection. The selected red wine was analyzed using HPLC; and the inhibitory effects of the wine and phenolic components were tested independently in a screening assay. Further analyses were conducted for the strongest inhibitors at physiologically relevant concentrations. Control experiments were conducted to determine the effects of the ethanol on UGT2B17.ResultsOver the concentration range of 2 to 8%, the red wine sample inhibited the glucuronidation of testosterone by up to 70% over 2 hours. The ethanol content had no significant effect. Three red wine phenolics, identified by HPLC analyses, also inhibited the enzyme by varying amounts in the order of quercetin (72%), caffeic acid (22%) and gallic acid (9%); using a ratio of phenolic:testosterone of 1:2.5. In contrast p-coumaric acid and chlorogenic acid had no effect on the UGT2B17. The most active phenolic was selected for a detailed study at physiologically relevant concentrations, and quercetin maintained inhibitory activity of 20% at 2 μM despite a ten-fold excess of testosterone.ConclusionThis study reports that in an in vitro supersome-based assay, the key steroid-metabolizing enzyme UGT2B17 is inhibited by a number of phenolic dietary substances and therefore may reduce the rate of testosterone glucuronidation in vivo. These results highlight the potential interactions of a number of common dietary compounds on testosterone metabolism. Considering the variety of foodstuffs that contain flavonoids, it is feasible that diet can elevate levels of circulating testosterone through reduction in urinary excretion. These results warrant further investigation and extension to a human trial to delineate the health implications.

Role of β-Adrenergic Receptors in the Oral Activity of Zinc-α2-Glycoprotein (ZAG)

Zinc-α2-glycoprotein (ZAG) is an adipokine with the potential as a therapeutic agent in the treatment of obesity and type 2 diabetes. In this study we show that human ZAG, which is a 41-kDa protein, when administered to ob/ob mice at 50 μg/d(-1) orally in the drinking water produced a progressive loss of body weight (5 g after 8 d treatment), together with a 0.5 C increase in rectal temperature and a 40% reduction in urinary excretion of glucose. There was also a 33% reduction in the area under the curve during an oral glucose tolerance test and an increased sensitivity to insulin. These results were similar to those after iv administration of ZAG. However, tryptic digestion was shown to inactivate ZAG. There was no evidence of human ZAG in the serum but a 2-fold elevation of murine ZAG, which was also observed in target tissues such as white adipose tissue. To determine whether the effect was due to interaction of the human ZAG with the β-adrenergic (β-AR) in the gastrointestinal tract before digestion, ZAG was coadministered to ob/ob mice together with propanolol (40 mg/kg(-1)), a nonspecific β-AR antagonist. The effect of ZAG on body weight, rectal temperature, urinary glucose excretion, improvement in glucose disposal, and increased insulin sensitivity were attenuated by propanolol, as was the increase in murine ZAG in the serum. These results suggest that oral administration of ZAG increases serum levels through interaction with a β-AR in the upper gastrointestinal tract, and gene expression studies showed this to be in the esophagus.

Reduction of urinary levels of N-telopeptide correlates with treatment compliance in women with postmenopausal osteoporosis receiving alendronate

The aim of this study was to assess the factors associated with the effectiveness of treatment with alendronate (ALN) quantified by a reduction in urinary excretion of N-telopeptide (NTx). The study is an observational, prospective, multicenter trial, with a 6-month follow-up. Postmenopausal osteoporotic women (densitometric criteria), who initiated treatment with ALN (70 mg/weekly) without previous treatment with antiresorptive agents (12 month) and calcitonin (6 month), were included. The assessment of NTx levels (nmol bone collagen equivalents/mmol creatinine) in the urine was performed at baseline and after completion of follow-up. A logistic regression model included "achieving a reduction in urinary NTx of at least 30% (minimal clinically significant change [MCSC])" as a dichotomous dependent variable and the following as independent variables: baseline urinary NTx levels, treatment compliance, years since diagnosis of menopause, ALN treatment duration, and treatment with calcium and vitamin D. Treatment compliance was assessed as the percentage of days of medication prescribed as a function of the time between the beginning and end of treatment. Good compliance was defined as a percentage between 80% and 120%. The variables that reached statistical significance were baseline urinary NTx values (odds ratio, 1.052; 95% CI, 1.025-1.079) and compliance (odds ratio, 3.9; 95% CI, 1.5-10.1). Therefore, the women with good treatment compliance were almost 4 times more likely to achieve an MCSC in NTx levels, and the raise in one unit of urinary NTx baseline values increased by 5% of the probability of achieving MCSC. Treatment with ALN (70 mg/week) in women with postmenopausal osteoporosis effectively reduces the urinary excretion of the bone turnover biomarker NTx. The probability of achieving a clinically significant reduction is greater in those women with higher baseline levels of NTx and in women who comply with treatment.

New clinical trials with vitamin D and analogs in renal disease

Two new clinical trials highlight refinements in the use of vitamin D and its analogs in the treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD), and the treatment of proteinuria in diabetics. In patients with ESRD, alfacalcidol is as effective as paricalcitol in suppressing parathyroid hormone; the occurrence of hypercalcemia and hyperphosphatemia is infrequent and similar with the two analogs. Oral cholecalciferol reduces albuminuria and urinary transforming growth factor-β1 in patients with type 2 diabetes mellitus and proteinuria.

The Effect of Immunization with Protein-sulphanilic Acid Conjugate on Sulphanilic Acid Disposition in the Rat

Rats were immunized with bovine gamma-globulin-sulphanilic acid conjugate and the plasma concentration of sulphanilic acid examined after an intravenous injection of this drug. There was a significant increase in plasma half-life and AUC and a significant decrease in clearance of sulphanilic acid in the immunized rats compared with the control. In the immunized rats, binding of sulphanilic acid to macromolecules in serum, determined by ultrafiltration, decreased with increase of sulphanilic acid concentration. At low concentrations, there was a significant increase in % binding of the drug in the serum of immunized rats compared with controls. There was also a significant reduction in urinary excretion of total drug in the immunized rats compared with controls. These findings suggest that sulphanilic acid-specific antibodies in the serum of immunized animals bind [14C]sulphanilic acid, giving rise to higher serum levels thereby making it unavailable for normal excretory processes.

Cystone in cystine stone formers

This is in response to a trial conducted by Dr. Erickson at Mayo Clinic in a paper titled ‘‘Cystone for one year did not change urine chemistry or decrease stone burden in cystine stone formers’’ [1]. This paper describes the results of clinical evaluation of Cystone in 10 patients. One of the important shortcomings of the study is inclusion of patients with cystine stones of long-standing duration, and probably had undergone every possible treatment. The authors mention that these were refractory patients particularly difficult to treat. When these patients did not respond to medical treatment for sufficient duration, it may not be appropriate to include them in this type of study. It is almost impossible to dislodge an impacted stone with medication and invariably requires surgical intervention. Despite a small number of patients included in this study, the biochemical data is available only for 12 out of 20 observations indicating that the data collection is insufficient for statistical evaluation. A careful analysis of this limited data does indicate that there is a trend in diuresis and reduction in urinary excretion of cystine, though it does not meet the statistical significance. This study was initiated because the authors met a patient with cystine stone who had experienced a near miraculous cure. Probably the author was curious to investigate whether Cystone is a ‘‘Miracle Cure’’. Miracle cure rarely exists in science, but makes no mistake, once a miracle is published in a peer-reviewed medical journal; the damage has already been done [2]. Cystone has never been claimed as a miracle cure. It is claimed to be effective in the management of nephrolithiasis wherein the stone size is \1.5 cm [3, 4]. The question is not about the efficacy of Cystone, but the way the clinical trial was designed and executed leading to ambiguous and conflicting results. A well-designed study should include a larger population size which follow Gaussian distribution baseline so as to increase the statistical strength in discriminating the efficacy or otherwise.

Coffee hull in the diet of dairy heifers: nitrogen balance and microbial protein synthesis

It was evaluated nitrogen compounds and microbial protein synthesis in heifers fed diets containing coffee hulls (0.0; 8.75; 17.25; and 26.25% of dry matter) replacing ground corn concentrate at the following levels of coffee hulls in the total diet dry matter: 0.0, 3.5, 7.0 or 10.5%. It was used 24 crossbreed heifers (7/8, 15/16 and 31/32 Holstein-Zebu), which were distributed in a random block design made up accordingly to the weight of the animals. Spot samples of urine were colleted aproximatelly four hours after morning feeding and were used to estimate microbial protein synthesis by using urine purine derivatives. It was not observed effect of coffee hull levels in the diet on total nitrogen intake (160 g/day) and nitrogen excretion in the urine (87.4 g/day). The inclusion of coffee hull in the diet linearly increased nitrogen excretion in feces, as well as nitrogen balance. There was linear reduction in urinary excretion of allantoin, in total purine derivative and absorbed purine, which reduced 0.715, 0.873, and 0.954 mmol/day to each coffee hull unity added to the concentrate, respectively. Coffee hull altered microbial protein synthesis, which reduced in 0.687 g/day to each coffee hull unity added to the concentrate. Reduction in microbial protein synthesis can reduce weight gain in heifers fed coffee hulls.

Rasburicase in the treatment of hyperuricemia of newborns

Sirs,The article by Hobbs and coworkers [1] provides scientificevidence for what we believe is a common clinical practice:the use of rasburicase in hyperuricemic newborns withacute kidney injury (AKI).These authors retrospectively reviewed the charts of 7hyperuricemic infants with AKI, successfully treated with asingle dose of rasburicase (0.17±0.04 mg/kg).Duringthelastfewyearswealsoexperiencedtheefficacyand safety of rasburicase in 10 AKI newborns (7 boys, 3girls), with a mean (± SD) body weight of 1,226 g (± 644.4),born at 29.4 weeks (± 30 days) and with a mean age atadministration of therapy of 20.2 days (± 11.5). Six of themwere of very low birth weight (VLBW) and 9 werepremature (data not published).After a single intravenous dose of rasburicase (0.2 mg/kgin 30 min) we also observed a statistically significantdecrease in serum uric acid concentration of a mean levelranging from 14.5±3.6 mg/dl to 6.6±7.5 mg/dl (p<0.002).No side effects were recorded.Hobbs and coworkers reported a significant improvementin serum creatinine and urine output on day 1 followingrasburicase [1]. The authors seem to attribute these results tothe reduction in serum uric acid as described in oncologicalpatients with tumor lysis syndrome (TLS) [2–4]. These dataare not confirmed by our study. We believe that uric acidplays a pathogenetic role in AKI secondary to TLS, while, asin the series by Hobbs et al., our patient’s uric acid increasedas a consequence of a reduction in urinary excretion, ratherthan overproduction. In fact, if we analyze each patientseparately it can be speculated that the specific therapy of theunderlying diseases, such as rehydration, is the main factorexplaining the improvement in serum creatinine and urineoutput, as evidenced by the sharp decrease in blood ureanitrogen and the improvement in urine output (in patients 1,3, and 7) after rehydration and/or resuscitation. Moreover, in2 cases (patients 2 and 4) serum creatinine remainedsignificantly high during the first week after treatment.At present, various studies have confirmed that rasburi-case is effective in reducing uric acid concentration and iswell tolerated [1, 4, 5], even in the neonatal period [3] andin premature newborns, as shown by our experience.References

Beneficial effect of pioglitazone in proteinuric IgA nephropathy with concomitant ACEI/ARB treatment.

Methods: Forty-one biopsy-proven IgAN patients with proteinuria (>0.5g/day) who were currently treated with renin angiotensin system inhibitors and had at least two out of four risk factors for progressive disease (male gender, blood pressure >150/90 mmHg, creatinine clearance of 20-80 mL/min/1.73m 2 , and chronicity index >1) were randomly assigned to receive either PGZ 30 mg/day (PGZ group; n=21) or placebo (control group, n=20) for 16 weeks. Results: Baseline characteristics of patients in both groups were comparable. Following 16-week treatment, proteinuria in the PGZ group was significantly lower than the control group, [1.2 vs. 2.1 g/day (p<0.05)]. Patients in the PGZ group also showed a significant reduction in urinary excretion of TGF-β (from 361.4 to 234.4 ng/gCr) and VEGF (from 1353.1 to 765.1 ng/gCr) after 16-week treatment (p<0.05, both). Conclusion: PGZ significantly reduced proteinuria, urinary TGF-β, and urinary VEGF in IgAN patients. These findings suggest that PGZ could have a role in the treatment of proteinuric IgAN. Further studies with larger cases and longer follow-up time are warranted.

Reduction in urinary excretion of neutrophil gelatinase-associated lipocalin by angiotensin receptor blockers in hypertensive patients

Reduction in urinary excretion of neutrophil gelatinase-associated lipocalin by angiotensin receptor blockers in hypertensive patients

Sex hormones and bile acids in intrahepatic cholestasis of pregnancy

Sex hormones and bile acids in intrahepatic cholestasis of pregnancy

Therapeutic Effect of Artemether in an Experimental Model of Nephrosis

This study was carried out to elucidate the therapeutic efficacy of a new antimalarial drug, artemether, in adriamycin-induced nephropathy. To induce experimental nephrosis, adriamycin was given once by a single intravenous injection through the tail vein. Six days after adriamycin injection, therapeutic protocol was developed by intramuscular (i.m.) administration of 5 mg/kg artemether (ART). The total of i.m. injections were 14, in which five injections were made every day and nine injections were carried out at regular 48-h intervals. The therapeutic protocol was terminated on day 28, and animals were sacrificed on day 49. Our results showed that treatment with ART caused a significant reduction in the level of proteinuria (118 ± 15 vs. 48 ± 21 mg/24 h), urine urea (723 ± 226 vs. 414 ± 185 mg/dL), and urine sodium (38 ± 8 vs. 28 ± 6 mEq/L) compared with nontreated controls. In addition, a decrease in serum cholesterol (250 ± 58 vs. 163 ± 58 mg/dL) and creatinine (1.4 ± 0.2 vs. 0.9 ± 0.2 mg/dL) and an increase in the level of serum albumin (3.3 ± 0.5 vs. 5.6 ± 0.5 g/dL) were significant in the group treated with ART compared with the patient group. Moreover, treatment with ART significantly reduced glomerular PMN and mononuclear cells infiltration, hypercellularity, karyorrhexis, wire loops and hydropic change in the capillary network within the renal cortex, as well as decreased hyalin casts. On the other hand, healthy controls receiving ART showed a significant decrease in amounts of serum triglyceride (174 ± 55 vs. 88 ± 27mg/dL), urine urea (720 ± 113 vs. 511 ± 211 mg/dL), urine sodium (45 ± 5 vs. 26 ± 6 mEq/L), and potassium (71 ± 14 vs. 53 ± 6 mEq/L) compared with the normal group, where significant reduction of urinary excretion of sodium and urea must be considered as a side effect of ART therapy. These data suggest that artemether therapy can ameliorate proteinuria and suppress the progression of glomerular lesions in an experimental model of nephrosis, and that it may be recommended as a lipid-lowering drug.

Effects of hepatic injury or kidney injury on the tryptophan–niacin metabolism in rats

Abstract Hepatic α-amino-β-carboxymuconate-e-semialdehyde decarboxylase (ACMSD) plays a key role in regulating NAD biosynthesis. In normal rats, ACMSD has been generally detectable only in the liver and kidneys. Therefore, there is a possibility that liver or kidney injury affects tryptophan–niacin metabolism. We previously reported the significant change of tryptophan–niacin metabolism in rats with liver cirrhosis or in rats with d -galactosamine injected liver injury. In this experiment, we investigated the change of tryptophan–niacin metabolism in rats treated with puromycin aminonucleoside (PAN)-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan–niacin conversion. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. The reduction of urinary excretion of niacin in nephrotic rats may be due to the reduction of blood tryptophan concentration. The role of the kidney ACMSD may be insignificant concerning tryptophan–niacin conversion under this experimental condition.

An NMR-based metabonomic investigation on effects of milk and meat protein diets given to 8-year-old boys

The objective of the study was to investigate the ability of an NMR-based metabonomic approach, applied to biofluids, to explore and identify overall exogenous and endogenous biochemical effects of a short-time high intake of milk protein or meat protein given to prepubertal children, the aim being to compare relative differences and not an absolute quantification. A total of twenty-four 8-year-old boys were asked to take 53 g protein as milk (n 12) or meat daily (n 12). At baseline and after 7 d, urine and serum samples were collected and high-resolution 1H NMR spectra were acquired on these using a 800 MHz spectrometer. The milk diet reduced the urinary excretion of hippurate, while the meat diet increased the urinary excretion of creatine, histidine and urea. The NMR measurements on serum revealed minor changes in the lipid profile, which most probably should be ascribed to an increase in the content of SCFA in the blood after consumption of the milk diet. The meat diet had no effect on the metabolic profile of serum. The study for the first time demonstrates the capability of proton NMR-based metabonomics to identify the overall biochemical effects of consumption of different animal proteins. The urine metabolite profile is more susceptible to perturbations as a result of short diet interventions than the serum metabolite profile. The milk diet-induced reduction in urinary excretion of hippurate suggests alterations in gut microflora, which may be useful information for further studies elucidating the effects of bioactive components in milk.