Protective impacts of Artemisia annua against hepatic toxicity induced by gentamicin.

The current study aimed to investigate the ameliorative effects of Artemisia annua (RA) extract on hepatic toxicity induced by gentamicin injection mice. Sixteen mice were divided into four groups; the control group received saline, the second group received 1% A. annua (RA) extract, third group injected 80 mg/kg gentamicin (GEN) intraperitoneally. The protective group treated with a combination of GEN and A. annua. All mice were treated for consecutive 15 days. Results confirmed that hepatic biomarkers (GPT, GCT, GOT, IL-6 and IL-1ß), all were altered after gentamycin injection. The histological analysis confirmed that gentamycin injected mice showed portal vein congestion, micro and macro steatosis, and nuclear pyknosis of hepatocytes. The protective group showed intact central vein with less microsteatosis of some hepatocytes. Immunochemistry analysis confirmed that the immunoreactivity of COX-2 gene showed negative impact in examined groups. Unlike, NF-κB gene exhibited diffuse positive expression in the gentamicin group. TGF-ß1 immunoreactivity was mild positive in control and highly upregulated in gentamicin treated mice, all were normalized after RA administration. In conclusion, RA showed a beneficial impact against gentamycin induced hepatic toxicity at cellular and biochemical levels by regulating proteins and inflammatory markers associated with liver activity.

Logit model in prospective coronary heart disease (CHD) risk factors prediction in Saudi population.

Analysis through logistic regression explored to investigate the relationship between binary or multivariable ordinal response probability and in one or more explanatory variables. The main objectives of this study to investigate advanced prediction risk factor of Coronary Heart Disease (CHD) using a logit model. Attempts made to reduce risk factors, increase public or professional awareness. Logit model used to evaluate the probability of a person develop CHD, considering any factors such as age, gender, high low-density lipoprotein (LDL) cholesterol, low high-density lipoprotein (HDL) cholesterol, high blood pressure, family history of CHD younger than 45, diabetes, smoking, being post-menopausal for women and being older than 45 for men. Logit concept of brief statistics described with slight modification to estimate the parameters testing for the significance of the coefficients, confidence interval fits the simple, multiple logit models. Besides, interpretation of the fitted logit regression model introduced. Variables showing best results within the scientific context, good explanation data assessed to fit an estimated logit model containing chosen variables, this present experiment used the statistical inference procedure; chi-square distribution, likelihood ratio, Score, or Wald test and goodness-of-fit. Health promotion started with increased public or professional awareness improved for early detection of CHD, to reduce the risk of mortality, aimed to be Saudi vision by 2030.

Protective effect of Acorus calamus on kidney and liver functions in healthy mice.

Acorus calamus (AC), is an herbal medicine commonly used as traditional practice in pharmacological applications. Present study initiated was evident to proof the hepatoprotective and nephroprotective activity with supporting histopathological status of kidneys and liver. Investigation done with the 5% (w/v) of AC dissolved in tap water (50 g/l) given for 15 days compared with control tap water to 5-7 week old C57Bl/6 mice both sexes. Renal function, liver function, biochemical and complete blood count was evaluated. AC significantly reduced food intake, body weight, also plasma concentration of electrolytes such as Na+, K+, Ca2+, were reduced as the excretion of electrolytes were increased in urine, significantly increased Fluid Intake, with Urinary urea, Urinary creatinine, Glomerular Filtration Rate, creatinine clearance, High-density lipoproteins, Mean Corpuscular Volume. The biochemical findings showed the hepatoprotective and histopathological changes showed the nephroprotective nature of AC by normal structure with no necrosis.

Eye lens and thyroid gland radiation exposure for patients undergoing brain computed tomography examination.

This study aims to estimate the effective radiation dose and organ dose from head CT procedures. It was conducted in three main private hospitals in Khartoum State-Sudan, using Toshiba machines with 64 slices. The total number of patients included in this study was 142 patients (82 males and 60 females). The effective dose and organ dose were calculated by CT Expo software. The effective dose slightly varied among patients according to gender and age. The effective dose for female patients (5.99 mSv) was higher than that for male patients (5.84 mSv), and the pediatric dose (5.46 mSv) was lower than the adults' dose (5.94 mSv). The dose for eye lens was found lower for male patients (89.117 mSv) than the dose for female patients (94.62) mSv). According to patients' age: the dose received by the lens of the eye was much lower in pediatric (79.93 mSv) than the adults (92.41 mSv). The dose for thyroid in female patients (33.52 mSv) was higher than the male patients (28 mSv). The pediatric dose (28.34 mSv) was lower than the adults' dose (30.64 mSv). Departmental imaging protocol and lack of training among hospital staff are expected to be responsible for these variations. Therefore, this study recommends that the CT technologists be trained on suitable strategies to achieve dose optimization. Moreover, patients' doses must be monitored regularly.

Prospective breast cancer risk factors prediction in Saudi women.

Women's health is affected by breast cancer worldwide and Saudi Arabia (SA) is no exception. Malignancy has enormous consequences for social, psychological and public health. The aim of this study was to examine the risk factors for Saudi women from breast cancer using logistic regression models. In 135 patient cases for different stages of breast cancer was used to study case management, 270 healthy women from King Abd Alla Medical City, Mecca, SA were taken to predict the probability of women developing breast cancer, logistic regression was analyzed taking factors such as age, marital status, family history, parity, age at first full-term pregnancy, menopausal status, body mass index (BMI) and breast feeding. The logistic regression model showed that there are important risk factors (age, marital status, family history, parity, age at first full-term pregnancy, menopausal status, body mass index, and breast feeding) in development of breast cancer. Fewer cases were observed in unmarried women, age ≤30, BMI ≤20. In contrast, more cases were found with women age 41-50 married, BMI > 30, a smaller number of children, not breast feeding, age of first pregnancy ≥30, menopausal status age at 46-50. Based on our data there is role of risk factors in developing breast cancer, less BMI, the increase number of children, breast feeding, which are playing as protective factor for breast cancer.

Comparative efficacy of Gum Arabic (Acacia senegal) and Tribulus terrestris on male fertility.

In this study the effect of Gum arabic (Acacia Senegal) was systemically targeted at male fertility with two experiments, the first comparing the effectiveness of Gum arabic (GA) and Tribulus terrestris (TT). For the first experiment, 27 adult mice Balb / c (18 females, 9 males) were divided into 3 in each group, one male and two females, group one had the usual tap water as power, group two had 5% (w / v) GA and group three had 5% (w / v) of TT for 21 days. The results showed, the number of offspring was more with GA treated when compared to TT treated. Blood measurements of testosterone showed significant increase in the GA group as compared to other groups, also Histopathological analysis showed the dose dependent 5% GA had normal seminiferous tubules with increase spermatogenesis. In this study the enhanced fertility in GA-treated mice Balb/c was observed and the experimental studies also show that GA fertility was increased.

Renal and extrarenal effects of gum arabic ( Acacia senegal )--what can be learned from animal experiments?

Gum arabic (GA), a water-soluble dietary fiber rich in Ca(2+), Mg(2+) and K(+), is used in Middle Eastern countries for the treatment of patients with chronic kidney disease. Recent animal experiments shed some light into mechanisms involved in the therapeutic action of GA. According to experiments in healthy mice, GA treatment increases creatinine clearance, enhances renal excretion of ADH, Mg(2+) and Ca(2+), decreases plasma phosphate concentration as well as urinary excretion of phosphate and Na(+). In diabetic mice GA treatment increases urinary Ca(2+) excretion, and decreases plasma phosphate concentration, plasma urea concentration, urinary flow rate, natriuresis, phosphaturia, glucosuria, proteinuria as well as blood pressure. Extrarenal effects of GA treatment in mice include decreased expression of intestinal Na(+) coupled glucose carrier SGLT1 with subsequent delay of electrogenic intestinal glucose transport, glucose-induced hyperglycemia, hyperinsulinemia and body weight gain. GA treatment decreases colonic transcription of the angiogenetic factors angiogenin 1, angiogenin 3 and angiogenin 4, of CD38 antigen, aquaporin4, interleukin18, vav-3-oncogene, y(+)-amino acid-transporter, sulfatase1, ubiquitinD and chemokine ligand5. Moreover, GA treatment decreases angiogenin and ß-catenin protein expression. Accordingly, GA treatment counteracts the development of tumors following chemical cancerogenesis. In mouse dendritic cells, antigen-presenting cells linking innate and adaptive immunity, GA treatment modifies maturation and cytokine release. GA treatment further favourably influences the course of murine malaria. The effects of GA treatment on plasma phosphate concentration, blood pressure and proteinuria may prove beneficial in chronic renal failure and diabetic nephropathy. The effect of GA on intestinal glucose transport may be useful in the prophylaxis and treatment of obesity and diabetes, the effect of GA on angiogenin and ß-catenin expression could be exploited for the prophylaxis against colon carcinoma, the effects of GA on angiogenin expression and dendritic cells may be useful in the treatment of inflammatory disease and malaria.

Effects of gum arabic (Acacia senegal) on renal function in diabetic mice.

BACKGROUND/AIMS: Gum arabic (GA) is a Ca(2+)-, Mg(2+)- and K(+)-rich dietary fiber used for the treatment of patients with chronic kidney disease in Middle Eastern countries. In healthy mice, GA treatment increases creatinine clearance, renal ADH excretion, as well as intestinal and renal excretion of Mg(2+) and Ca(2+). GA decreases plasma Pi concentration, urinary Pi and Na(+) excretion. The present study explored the effects of GA on renal function in diabetic mice. METHODS: Metabolic cage experiments were performed on Akita mice (akita(+/-)), which spontaneously develop insulin deficiency and thus hyperglycemia. Plasma and urinary concentrations of Na(+), K(+) and Ca(2+) were measured by flame photometry (AFM 5051, Eppendorf, Germany), creatinine by the Jaffé method, phosphate photometrically, urea by an enzymatic method, glucose utilizing a glucometer and an enzymatic kit, aldosterone using an RIA, urinary albumin fluorometrically, and blood pressure by the tail-cuff method. RESULTS: GA (10% in drinking water) significantly increased urinary excretion of Ca(2+) and significantly decreased plasma phosphate and urea concentrations, urinary flow rate, urinary Na(+), phosphate and glucose excretion, blood pressure and proteinuria. CONCLUSIONS: GA treatment decreases blood pressure and proteinuria in diabetic mice and may thus prove beneficial in diabetic nephropathy.

Anti-malarial effect of gum arabic.

BACKGROUND: Gum Arabic (GA), a nonabsorbable nutrient from the exudate of Acacia senegal, exerts a powerful immunomodulatory effect on dendritic cells, antigen-presenting cells involved in the initiation of both innate and adaptive immunity. On the other hand GA degradation delivers short chain fatty acids, which in turn have been shown to foster the expression of foetal haemoglobin in erythrocytes. Increased levels of erythrocyte foetal haemoglobin are known to impede the intraerythrocytic growth of Plasmodium and thus confer some protection against malaria. The present study tested whether gum arabic may influence the clinical course of malaria. METHODS: Human erythrocytes were in vitro infected with Plasmodium falciparum in the absence and presence of butyrate and mice were in vivo infected with Plasmodium berghei ANKA by injecting parasitized murine erythrocytes (1 × 106) intraperitoneally. Half of the mice received gum arabic (10% in drinking water starting 10 days before the day of infection). RESULTS: According to the in vitro experiments butyrate significantly blunted parasitaemia only at concentrations much higher (3 mM) than those encountered in vivo following GA ingestion (<1 µM). According to the in vivo experiments the administration of gum arabic slightly but significantly decreased the parasitaemia and significantly extended the life span of infected mice. DISCUSSION: GA moderately influences the parasitaemia and survival of Plasmodium-infected mice. The underlying mechanism remained, however, elusive. CONCLUSIONS: Gum arabic favourably influences the course of murine malaria.

Activation of membrane androgen receptors in colon cancer inhibits the prosurvival signals Akt/bad in vitro and in vivo and blocks migration via vinculin/actin signaling.

Recently, we reported that membrane androgen receptors (mARs) are expressed in colon tumors triggering strong apoptotic responses. In the present study, we analyzed mAR-induced downstream effectors controlling cell survival and migration of Caco2 colon cancer cells. We show that long-term activation of mAR downregulated the activity of PI-3K and Akt and induced de-phosphorylation/activation of the proapoptotic Bad (p-Bad). Moreover, treatment of APC(Min/+) mice, which spontaneously develop intestinal tumors, with mAR-activating testosterone conjugates reduced the tumor incidence by 80% and significantly decreased the expression of p-Akt and p-Bad levels in tumor tissue. Furthermore, mAR activation strongly inhibited Caco2 cell migration. In accordance with these findings, vinculin, a protein controlling cell adhesion and actin reorganization, was effectively phosphorylated upon mAR activation. Phosphorylation inhibitors genistein and PP2 inhibited actin reorganization and restored motility. Moreover, silencing vinculin by appropriate siRNA's, or blocking actin reorganization by cytochalasin B, restored the migration potential. From these results we conclude that mAR activation inhibits the prosurvival signals Akt/Bad in vitro and in vivo and blocks migration of colon cancer cells via regulation of vinculin signaling and actin reorganization, supporting the powerful tumoristatic effect of those receptors.

Downregulation of angiogenin transcript levels and inhibition of colonic carcinoma by gum arabic (Acacia senegal).

Gum Arabic (GA), a nutrient from dried exudate of Acacia senegal, is widely used as emulsifier and stabilizer. It stimulates sodium and water absorption in diarrhea. This study explored the effects of GA in colonic tissue. Mice were treated with GA (10% wt/vol) in drinking water and gene array was performed. As GA modified several tumor-relevant genes, chemical cancerogenesis (intraperitoneal injection of 20 mg/kg 1,2-dimethylhydrazine followed by 3 cycles of 3% dextrane sodium sulphate in drinking water) was induced with or without GA treatment. Within 4 days, GA treatment decreased the colonic transcript levels of the angiogenetic factors angiogenin 1, angiogenin 3, and angiogenin 4 by 78 +/- 18%, 88 +/- 15%, and 92 +/- 13%, respectively (n = 5 each), and of further genes including CD38 antigen, aquaporin4, interleukin18, vav-3-oncogene, gamma(+)-amino acid transporter, sulfatase1, ubiquitinD, and chemokine ligand5. According to Western blotting, GA treatment similarly decreased angiogenin protein expression, and according to immunohistochemistry, it decreased ss-catenin expression. Chemical cancerogenesis resulted in multiple colonic tumors within 12 wk. GA treatment (10% wt/wt) in drinking water significantly decreased the number of tumors by 70%. The observations disclose a powerful anticarcinogenic effect of GA. The nutrient could thus be used for the prophylaxis against colon carcinoma particularly in individuals at enhanced risk.

Stimulation of mouse dendritic cells by Gum Arabic.

Gum Arabic (GA), a nonabsorbable nutrient manufactured from the exudate of Acacia senegal, is composed of a complex polysaccharide. GA is used by the pharmaceutical and food industry as an emulsifier but may, at an appropriate dosage, modify intestinal transport. Dendritic cells (DCs) can protrude between epithelial cells and sense the composition of the lumen. As DCs are stimulated by bacterial polysaccharides, we hypothesized that GA may similarly stimulate DCs. To test that hypothesis, mouse DCs were treated with either LPS or GA and expression of maturation markers, phagocytotic activity, cytokine production and ability to stimulate CD4(+) T cells in allogenic mixed leukocyte reaction (allo-MLR) was analyzed. As a result both LPS and GA increased the percentage of CD11c(+)CD86(+), CD11c(+)MHCII(+), CD11c(+)CD40(+), CD54-expressing DCs and decreased their phagocytic activity. Both LPS and GA stimulated the production of IL-6, IL-10, IL12p70 and TNFalpha in a p38- and/or ERK-dependent manner. GA treatment led to an enhanced IL-10 secretion, whereas LPS was more effective on IL-6 and IL-12p70 production. Both LPS- and GA-stimulated DCs enhanced CD4(+) T cell proliferation but the profile of cytokines produced in allo-MLR was different. High levels of IL-10 and IL-6 were observed in the presence of GA-treated DCs, whereas IFN-gamma and IL-12p70 production was similar with LPS- or GA-treated DCs. LPS upregulated p38 and transiently ERK1/2, while GA led to more sustained activation of ERK1/2, only. In conclusion, the observations reveal a powerful immunomodulatory effect of GA.

Downregulation of mouse intestinal Na(+)-coupled glucose transporter SGLT1 by gum arabic (Acacia Senegal).

Intestinal Na(+)-coupled glucose transporter SGLT1 determines the rate of glucose transport, which in turn influences glucose-induced insulin release and development of obesity. The present study explored effects of Gum Arabic (GA), a dietary polysaccharide from dried exudates of Acacia Senegal, on intestinal glucose transport and body weight in wild-type C57Bl/6 mice. Treatment with GA (100 g/l) in drinking water for four weeks did not affect intestinal SGLT1 transcript levels but decreased SGLT1 protein abundance in jejunal brush border membrane vesicles. Glucose-induced jejunal short-circuit currents revealed that GA treatment decreased electrogenic glucose transport. Drinking a 20% glucose solution for four weeks significantly increased body weight and fasting plasma glucose concentrations, effects significantly blunted by simultaneous treatment with GA. GA further significantly blunted the increase in body weight, fasting plasma glucose and fasting insulin concentrations during high fat diet. In conclusion, the present observations disclose a completely novel effect of gum arabic, i.e. its ability to decrease intestinal SGLT1 expression and activity and thus to counteract glucose-induced obesity.

SGK1-dependent intestinal tumor growth in APC-deficient mice.

Adenomatous polyposis coli (APC) is inactivated in familial adenomatous polyposis and sporadic colorectal cancer. Mice carrying defective APC (apc(Min/+)) spontaneously develop gastrointestinal tumors. APC binds GSK3beta, which phosphorylates beta-catenin thus fostering its degradation. beta-catenin upregulates the serum- and glucocorticoid-inducible kinase Sgk1, which inhibits GSK3beta. The present study explored the role of SGK1 in tumor growth of apc(Min/+)mice. apc(Min/+)mice were crossed with SGK1-knockout mice (sgk1(-/-)) and their wild type littermates (sgk1(+/+)) generating apc(Min/+)/sgk1(-/-)mice and apc(Min/+)/sgk1(+/+)mice. beta-catenin abundance was determined by Western blotting and confocal microscopy. As a result apc(Min/+)/sgk1(+/+)mice developed significantly more intestinal tumors than apc(Min/+)/sgk1(-/-)mice. Following chemical cancerogenesis, colonic beta-catenin protein abundance was significantly higher in sgk1(+/+)mice than in sgk1(-/-)mice. beta-catenin expression was significantly increased in HEK293 cells treated with dexamethasone for upregulation of Sgk1. In conclusion, SGK1 expression favors the development of intestinal tumors in APC-deficient mice, an effect at least partially due to enhanced beta-catenin protein abundance.

Functional membrane androgen receptors in colon tumors trigger pro-apoptotic responses in vitro and reduce drastically tumor incidence in vivo.

BACKGROUND: Membrane androgen receptors (mAR) have been implicated in the regulation of cell growth, motility and apoptosis in prostate and breast cancer. Here we analyzed mAR expression and function in colon cancer. RESULTS: Using fluorescent mAR ligands we showed specific membrane staining in colon cell lines and mouse xenograft tumor tissues, while membrane staining was undetectable in healthy mouse colon tissues and non-transformed intestinal cells. Saturation/displacement assays revealed time- and concentration-dependent specific binding for testosterone with a KD of 2.9 nM. Stimulation of colon mAR by testosterone albumin conjugates induced rapid cytoskeleton reorganization and apoptotic responses, even in the presence of anti-androgens. The actin cytoskeleton drug cytochalasin B effectively inhibited the pro-apoptotic responses and caspase-3 activation. Interestingly, in vivo studies revealed that mAR activation resulted in a 65% reduction of tumor incidence in chemically induced Balb/c mice colon tumors. CONCLUSION: Our results demonstrate for the first time that functional mARs are predominantly expressed in colon tumors and that their activation results in induction of anti-tumor responses in vitro and extensive reduction of tumor incidence in vivo.

Relative resistance of SGK1 knockout mice against chemical carcinogenesis.

The serum and glucocorticoid inducible kinase SGK1 was originally cloned from mammary tumor cells. SGK1 was found to be up-regulated in a variety of tumors, but down-regulated in several distinct tumors. Thus, evidence for a role of SGK1 in tumor growth remained conflicting. According to in vitro observations, SGK1 is up-regulated by the oncogene beta-catenin and negatively regulates the proapoptotic transcription factor FOXO3a, which in turn stimulates transcription of the Bcl2-interacting mediator BIM. This study aimed to define the role of SGK1 in colon carcinoma in vivo. SGK1 knockout mice (sgk1(-/-)) and their wild type littermates (sgk1(+/+)) were subjected to chemical cancerogenesis (intraperitoneal injection of 20 mg/kg 1,2-dimethylhydrazine followed by three cycles of 30 g/L synthetic dextran sulfate sodium for 7 days). Moreover, SGK1 was silenced in HEK293 cells. FOXO3a and BIM protein abundance was determined by Western blotting and immunohistochemistry. Following chemical cancerogenesis, sgk1(-/-)mice developed significantly less colonic tumors than sgk1(+/+)mice. According to Western blotting and immunohistochemistry, SGK1 deficiency enhanced the expression of FOXO3a and BIM both, in vitro and in vivo. SGK1 deficiency counteracts the development of colonic tumors, an effect at least in part due to up-regulation of FOXO3a and BIM.

Responses to diuretic treatment in gene-targeted mice lacking serum- and glucocorticoid-inducible kinase 1.

BACKGROUND/AIMS: Serum- and glucocorticoid-inducible kinase 1 (SGK1) stimulates the epithelial sodium channel (ENaC), renal outer medullary K(+) channel 1, Na(+)/K(+)-ATPase and presumably the Na(+)-Cl(-) cotransporter (NCC). SGK1-deficient mice (sgk(-/-)) show a compensated salt-losing phenotype with secondary hyperaldosteronism. The present experiments explored the role of SGK1 in the response to diuretics. METHODS: sgk1(-/-) mice and their wild-type littermates (sgk1(+/+)) were treated with the ENaC blocker triamterene (200 mg/l), the Na(+)-K(+)-2Cl(-) cotransport inhibitor furosemide (125 mg/l), the NCC blocker hydrochlorothiazide (400 mg/l) and the mineralocorticoid receptor blocker canrenoate (800 mg/l) for 8 days. Renal SGK1 expression was studied using quantitative RT-PCR and immunofluorescence. RESULTS: Diuretic treatment increased SGK1 mRNA and protein expression in the kidney of wild-type sgk1(+/+) mice. The responses to furosemide, hydrochlorothiazide or canrenoate were not different between sgk1(+/+) and sgk1(-/-) mice, and were accompanied by moderate increases in plasma aldosterone and urea concentrations. However, treatment with triamterene in sgk1(-/-) mice (but not in sgk1(+/+) mice) led to severe, eventually lethal, body weight loss as well as increases in plasma aldosterone, urea and K(+) concentrations. CONCLUSIONS: SGK1 is required for diuretic tolerance to triamterene. The observations confirm the impaired kaliuretic potency of sgk1(-/-) mice and point to a role of SGK1 in renal Na(+) reabsorption by mechanisms other than ENaC.

APC sensitive gastric acid secretion.

Adenomatous polyposis coli (APC) is a tumor suppressor gene inactivated in familial adenomatous polyposis and sporadic colorectal cancer. Mice carrying a loss-of-function mutation in the apc gene (apc(Min/+)) spontaneously develop gastrointestinal tumors. APC fosters degradation of beta-catenin, which in turn upregulates the serum- and glucocorticoid-inducible kinase SGK1. SGK1 stimulates KCNQ1, which is required for luminal K+ recycling and thus for gastric acid secretion. BCECF-fluorescence was utilized to determine gastric acid secretion in isolated gastric glands from apc(Min/+) mice and their wild type littermates (apc(+/+)). Western blotting was employed to analyse beta-catenin and SGK1 expression and immunohistochemistry to determine KCNQ1 protein abundance. beta-catenin and SGK1 expression were enhanced in apc(Min/+) mice. Cytosolic pH was similar in apc(Min/+) mice and apc(+/+) mice. Na+-independent pH recovery following an ammonium pulse (DeltapH/min), which reflects H+/K+ ATPase activity, was, however, significantly faster in apc(Min/+) mice than in apc(+/+)mice. In both genotypes DeltapH/min was abolished in the presence of H+/K+ ATPase inhibitor omeprazole (100 microM). Treatment of apc(Min/+) and apc(+/+)mice with 5 microM forskolin 15 minutes prior to the experiment or increase in local K+-concentrations to 35 mM (replacing Na+/NMDG) significantly increased DeltapH/min and abrogated the differences between genotypes. The increase of DeltapH/min in apc(Min/+)mice required SGK1, as it was abolished by additional knockout of SGK1 (apc(Min/+)/sgk1(-/-)). In conclusion, basal gastric acid secretion is significantly enhanced in apc(Min/+)mice, pointing to a role of APC in the regulation of gastric acid secretion. The effect of APC requires H+/K+ ATPase activity and is at least partially due to SGK1-dependent upregulation of KCNQ1.

Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome.

Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.

Effects of gum arabic (Acacia senegal) on water and electrolyte balance in healthy mice.

OBJECTIVE: Gum arabic (GA) is a dietary fiber derived from the dried exudates of Acacia senegal. It is widely used in both the pharmaceutical and food industries as an emulsifier and stabilizer. It is also used in the traditional treatment of patients with chronic kidney disease in Middle Eastern countries. However, the effects of GA on renal function remain ill-defined. DESIGN: We explored the effects of GA on the water and electrolyte balance of healthy wild-type 129S1/SvImJ mice (n = 18). Feces and urine were collected in metabolic cages before and after 3 or 14 days of treatment with 10% GA in drinking water. RESULTS: The GA solutions contained particularly high concentrations of Ca2+, Mg2+, and K+. Because of enhanced uptake, treatment with GA significantly increased both the intestinal and renal excretion of Mg2+ and Ca(2+). The latter was accompanied by decreased urinary excretion of inorganic phosphate and decreased plasma concentrations of 1,25-dihydroxy vitamin D. Moreover, GA significantly increased fecal weight and Na+ excretion. Gum arabic increased 24-h creatinine clearance (from 283 +/- 35 to 382 +/- 40 muL/min [SEM]) and urinary antidiuretic hormone excretion, and decreased daily urine output (from 1.8 +/- 0.2 to 1.2 +/- 0.1 mL/24 h) as well as the urinary excretion of Na(+) (from 226 +/- 22 to 196 +/- 19 mumol/24 h). In conclusion, treatment with GA resulted in moderate but significant increases of creatinine clearance and altered electrolyte excretion, i.e., effects favorable in renal insufficiency.