struvite and Body-Weight

Diuron, a substituted urea herbicide, is carcinogenic to the urinary bladder of rats at high dietary levels. Its proposed carcinogenic mode of action (MOA) includes urothelial cytotoxicity and necrosis followed by regenerative cell proliferation and sustained urothelial hyperplasia. Cytotoxicity could be induced either by urinary solids or by chemical toxicity by diuron and/or metabolites excreted in the urine. Diuron was not genotoxic in a previous single-cell gel (comet) assay, but possible cross-linking activity remained to be evaluated. The present study explored the MOA of diuron and the effect of urinary acidification on the development of urothelial lesions. Male Wistar rats were fed diuron (2500 ppm, about 130 mg/kg of body weight) either with or without NH(4)Cl 10,000 ppm to acidify the urine. Reversibility of urothelial changes was also examined. The animals were euthanized after 15, 25, or 30 weeks. Diuron-fed rats had urinary amorphous precipitate and magnesium ammonium phosphate crystals similar to control animals. Groups treated with diuron + NH(4)Cl showed decreased urinary pH and reduced amounts of urinary crystals and precipitate. Urothelial necrosis and simple hyperplasia were observed by light microscopy and scanning electron microscopy both in diuron- and in diuron + NH(4)Cl-treated groups. Cytotoxicity and proliferative changes were mostly reversible. A modified comet assay developed in vitro with Chinese hamster ovary cells showed that diuron did not induce DNA cross-links. These data suggest that cytotoxicity with consequent regenerative cell proliferation is the predominant MOA for diuron rat urothelial carcinogenesis, the cytotoxicity being chemically induced and not due to urinary solids.

Topics: Ammonium Chloride; Animals; Body Weight; Carcinogens; Cell Proliferation; CHO Cells; Comet Assay; Cricetinae; Cricetulus; Diuron; DNA Damage; Herbicides; Hydrogen-Ion Concentration; Hyperplasia; Magnesium Compounds; Male; Necrosis; Phosphates; Rats; Rats, Wistar; Regeneration; Struvite; Time Factors; Urinary Bladder; Urinary Bladder Neoplasms; Urinary Calculi; Urothelium

To assess the effect of dietary potassium citrate supplementation on the urinary pH, relative supersaturation of calcium oxalate and struvite (defined as the activity product/solubility product of the substance), and concentrations of magnesium, ammonium, phosphate, citrate, calcium, and oxalate in dogs.. 12 healthy adult dogs.. Canned dog food was fed to dogs for 37 days. Dogs were randomly allocated to 3 groups and fed test diets for a period of 8 days. Study periods were separated by 6-day intervals. During each study period the dogs were fed either standard diet solus (control) or standard diet plus 1 of 2 types of potassium citrate supplements (150 mg potassium citrate/kg of body weight/d) twice daily. Urinary pH, volume and specific gravity, relative supersaturation of calcium oxalate and struvite, and concentrations of magnesium, ammonium, phosphate, calcium, oxalate, and citrate were assessed for each treatment.. Mean urine pH was not significantly affected by dietary potassium citrate supplementation, although urine pH did increase by 0.2 pH units with supplementation. Diets containing potassium citrate maintained a higher urine pH for a longer part of the day than control diet. Three Miniature Schnauzers had a significantly lower urinary relative calcium oxalate supersaturation when fed a diet supplemented with potassium citrate, compared with control diet.. Dietary potassium citrate supplementation has limited effects on urinary variables in most healthy dogs, although supplementation results in maintenance of a higher urine pH later in the day. Consequently, if supplementation is introduced, dogs should be fed twice daily and potassium citrate should be given with both meals or with the evening meal only.

Topics: Animals; Body Weight; Calcium Oxalate; Circadian Rhythm; Dogs; Energy Intake; Female; Hydrogen-Ion Concentration; Magnesium Compounds; Male; Phosphates; Potassium Citrate; Potassium, Dietary; Struvite; Urine

To examine effects of high-protein diets (> 50% crude protein of dry matter) on urinary mineral excretion and struvite activity product ([Mg2+] x [NH4+] x [PO(4)3-]).. 14 clinically normal cats, 4 adult female and male cats for experiments 1 and 2, respectively, and 6 female kittens aged 4 months for experiment 3.. Relations between dietary protein amount (25.9, 38.3, 51.4, and 65.4% crude protein [dry matter]) and urinary excretion of Mg, P, and Ca were examined in a 4 x 4-Latin square design (experiment 1). Struvite activity product, the index of solubility of struvite crystals, was determined when a high-protein diet (54.9%) was fed (experiment 2). Utilization of minerals in cats fed a high-protein diet long term was examined (experiment 3).. Water intake and urine volume increased with increasing dietary protein concentration. Urinary Mg2+ excretion was not affected (experiment 1) or was decreased (experiment 3) by higher protein intake, leading to lower urine Mg2+ concentration in groups fed higher protein amounts. Urine pH was decreased by high-protein intake. As a result, PO(4)3- concentration was decreased by high-protein intake (experiment 2), although total daily urinary excretion of P was increased. Consequently, struvite activity product tended to decrease in cats fed high-protein diets, indicating increase in struvite solubility. High-protein intake decreased Ca and P retention by increasing their fecal and urinary excretions, respectively.. As a consequence of the increase in urine volume and urine acidification, high-protein diets have potential ability to increase solubility of struvite crystals.

Topics: Animals; Body Weight; Calcium; Cats; Diet; Dietary Proteins; Diuresis; Female; Hydrogen-Ion Concentration; Magnesium; Magnesium Compounds; Male; Minerals; Phosphates; Phosphorus; Regression Analysis; Struvite