Effect of Flos carthami Extract and α 1-Adrenergic Antagonists on the Porcine Proximal Ureteral Peristalsis.

Traditional Chinese medicine (TCM) has been proposed to prevent urolithiasis. In China, Flos carthami (FC, also known as Carthamus tinctorius) (Safflower; Chinese name: Hong Hua/) has been used to treat urological diseases for centuries. We previously performed a screening and confirmed the in vivo antilithic effect of FC extract. Here, ex vivo organ bath experiment was further performed to study the effect of FC extract on the inhibition of phenylepinephrine (PE) (10(-4) and 10(-3) M) ureteral peristalsis of porcine ureters with several α 1-adrenergic antagonists (doxazosin, tamsulosin, and terazosin) as experimental controls. The results showed that doxazosin, tamsulosin, and terazosin dose (approximately 4.5 × 10(-6) - 4.5 × 10(-1) µg/mL) dependently inhibited both 10(-4) and 10(-3) M PE-induced ureteral peristalsis. FC extract achieved 6.2% ± 10.1%, 21.8% ± 6.8%, and 24.0% ± 5.6% inhibitions of 10(-4) M PE-induced peristalsis at doses of 5 × 10(3), 1 × 10(4), and 2 × 10(4) µg/mL, respectively, since FC extract was unable to completely inhibit PE-induced ureteral peristalsis, suggesting the antilithic effect of FC extract is related to mechanisms other than modulation of ureteral peristalsis.

Effects of commercial citrate-containing juices on urolithiasis in a Drosophila model.

Diet modification plays an important role in nephrolithiasis. Development of an easy, ready-to-use beverage such as a commercial juice drink to use as a preventive treatment for renal calculi formation would be widely welcomed. We previously developed a novel Drosophila model for the study of nephrolithiasis. It provides a new well-established drug discovery platform for this common disease. In our current study, we used the Drosophila model to investigate the preventive effects of various commercial juices as potential treatments for nephrolithiasis. Our results showed that apple, cranberry, orange, and pomegranate juices failed to reduce calcium oxalate (CaOx) crystal formation, whereas our positive control-potassium citrate (K-citrate)-significantly prevented CaOx crystal formation. Unlike the commercial fruit juices that were tested, the administration of K-citrate significantly ameliorated the ethylene glycol (EG)-induced life-span reduction in treated flies. These results indicate that EG-induced CaOx nephrolithiasis in Drosophila can be prevented by K-citrate, but not by commercial citrate-containing juices. However, the inhibitory capability of citrate-containing juices to reduce renal stone formation in humans requires further elucidation.

Melamine-induced urolithiasis in a Drosophila model.

Melamine-tainted food can induce renal stones in both humans and animals. We have previously reported a novel Drosophila model for the study of renal stone disease. In addition to hyperoxaluria-causing agents, we also tested herein the effect of melamine on crystal formation in Drosophila . The results indicate that administration of melamine alone caused crystal formation in a dose-dependent manner. The crystals also appeared after ingestion of melamine for 3 weeks in the Malpighian tubules of Drosophila when viewed with polarized light. Administration of potassium citrate (K citrate) was found to significantly ameliorate the melamine-induced reduction of lifespan. However, administration of K citrate failed to reduce the quantity of crystals. Because calcium oxalate is not the major crystal induced by melamine, the predominant components of melamine-induced crystals and the potential crystal inhibitors warrant further investigation.

Ethylene glycol induces calcium oxalate crystal deposition in Malpighian tubules: a Drosophila model for nephrolithiasis/urolithiasis.

Several animal species are used to study calcium oxalate urolithiasis; however, an ideal model has yet to be identified. We used Drosophila as a model organism and fed the flies lithogenic agents such as ethylene glycol, hydroxyl-L-proline, and sodium oxalate. At different times, the Malpighian tubules, the kidney equivalent of insects, were dissected and a polarized light microscope used to highlight the birefringent crystals. Scanning electron microscopy and energy-dispersive X-ray spectroscopy confirmed that the crystal composition was predominately calcium oxalate. Furthermore, administration of potassium citrate successfully reduced the quantity of and modulated the integrity of the ethylene glycol-induced crystals. Thus, the Drosophila model of bio-mineralization produces crystals in the urinary system through many lithogenic agents, permits observation of crystal formation, and is amenable to genetic manipulation. This model may mimic the etiology and clinical manifestations of calcium oxalate stone formation and aid in identification of the genetic basis of this disease.

Identification of melamine/cyanuric acid-containing nephrolithiasis by infrared spectroscopy.

Melamine-contaminated milk formula caused infant nephrolithiasis in some areas of China. Its combination with cyanuric acid causes crystallization in renal tubules. Following this renal damage and even renal failure that require long-term hemodialysis has been reported. Therefore, correct and timely diagnosis of these complex diseases is critical. Melamine containing stone is a combination of equal molar ratios of common stone compositions that has been reported from previous animal studies. We have previously identified the compositions of urinary tract stones with infrared (IR) spectroscopy. We hypothesized that the absorbance of wavelength of IR can identify melamine/cyanuric acid in the presence of mixing human stone compositions. In this study, we made an artificial stone composition and examine under IR absorbance by mixing equal molar ratios of melamine/cyanuric acid with different types of human urinary stones, and established a reference of IR analysis for the identification of melamine/cyanuric acid-containing human urinary tract stones. Knowledge of the precise stone composition allowed institution of appropriate prophylactic dietary and medical therapy and this may help in the prevention of urinary stone recurrence. The results are promising that melamine and cyanuric acid can be identified clearly in a low percentile (approximately 1%) of stone mixture pellet. Therefore, IR seems to be an ideal tool for the identification of melamine/cyanuric acid-containing stones.