Hydroalcoholic Extract of Ziziphus Jujuba Leaf to Prevent Ethylene Glycol and Ammonium Chloride-Induced Kidney Stones in Male Rat: Is it Effective?

PURPOSE: This study aimed to evaluate the effect of Ziziphus jujuba (Z. jujuba) leaf hydroalcoholic extract on the prevention/treatment of kidney stones. MATERIALS AND METHODS: Thirty-six male Wistar rats were randomly divided into six groups: control, Sham (kidney stone induction (KSI) by ethylene glycol 1% + ammonium chloride 0.25% through drinking water for 28 days), Prevention groups 1, 2 (KSI and Z. jujuba leaf (250 and 500 mg/kg, respectively) through gavage for 28 days), and Treatment groups 1, 2 (KSI and Z. jujuba leaf (250 and 500 mg/kg, respectively) from the 15th day). On the 29th day, the rats' 24-hour urine was assessed, the animals were weighed, and blood samples were taken. Finally, after nephrectomy and weighing the kidneys, tissue sections were prepared to examine the number of calcium oxalate crystals and tissue changes. RESULTS: The results indicated a significant increase in kidney weight and index, tissue changes, and the number of calcium oxalate crystals in the Sham group compared to the control; using Z. jujuba leaf considerably reduced them in experimental groups compared to the Sham. Body weight decreased in the Sham and experimental groups (except the prevention 2 group) compared to the control, while this observed reduction was lower in all experimental groups compared to the Sham. The mean urinary calcium, uric acid, creatinine, and serum creatinine in Sham and experimental groups (except the prevention 2 group) indicated a substantial increase compared to the control and decreased significantly in all experimental groups compared to the Sham. CONCLUSION: Hydroalcoholic extract of Z. jujuba leaf is effective in the reduction of calcium oxalate crystals forming, and its most effective dose was 500mg/kg.

Anti-urolithiatic Activity of Daidzin in Ethylene Glycol-Induced Urolithiasis in Rats.

Urolithiasis is a common urological disorder, which causes considerable morbidity in both genders at all age groups worldwide. Though treatment options such as diuretics and non-invasive techniques to disintegrate the deposits are available, but often they are found less effective in the clinics. In this work, we planned to investigate the ameliorative effects of daidzin against the ethylene glycol (EG)-induced urolithiasis in rats. The male albino rats were distributed into four groups (n = 6) as control (group I), urolithiasis induced by the administration of 0.75% EG (group II), urolithiasis induced rats treated with 50 mg/kg of daidzin (group III), and urolithiasis rats treated with standard drug 750 mg/kg of cystone (group IV). The urine volume, pH, and total protein in the urine were assessed. The activities of marker enzymes in both plasma and kidney tissues were analyzed using assay kits. The levels of kidney function markers such as calcium, oxalate, urea, creatinine, uric acid, magnesium, BUN, and phosphorous were estimated using assay kits. The status of antioxidants and inflammatory cytokines were also examined using kits. The renal tissues were examined by histopathological analysis. Our results revealed that the daidzin treatment effectively decreased the urine pH and protein level and increased the urine volume in the urolithiasis rats. Daidzin decreased the calcium, oxalate, uric acid, and urea, creatinine, and BUN levels and also improved the magnesium and phosphorus in the urolithiasis rats. The activities of AST, ALT, ALP, GGT, and LDH were effectively reduced by the daidzin in both serum and renal tissue. Daidzin also reduced the inflammatory marker and increased the antioxidant levels. Histopathology results also proved the therapeutic effects of daidzin. Together, our results displayed that daidzin is effective in the amelioration of EG-induced urolithiasis in rats.

Protective potential of Angelica sinensis polysaccharide extract against ethylene glycol-induced calcium oxalate urolithiasis.

PURPOSE: To evaluate a Angelica sinensis polysaccharide aqueous extract as a preventive agent in experimentally induced urolithiasis using in- vitro and vivo models. MATERIAL AND METHODS: Angelica sinensis polysaccharide was investigated in vitro to determine its antilithiatic effects on the formation and morphology of calcium oxalate (CaOx) crystals and was analyzed in vivo to determine its ability to prevent CaOx urolithiasis in rats subjected to ethylene glycol-induced urolithiasis. Potassium citrate administration was used in the positive control group. The urolithiasis-related biochemical parameters were evaluated in the rats urine, serum and kidney homogenates. Kidney sections were subjected to histopathological and immunohistochemical analyses, and urolithiasis-related phospho-c-Jun NH2-terminal protein kinase and kidney injury molecule-1proteins were evaluated by Western blot analyses. RESULTS: Angelica sinensis polysaccharide exhibited concentration-dependent inhibition of CaOx crystal formation. The in vitro assay revealed significant inhibition of crystal formation (6.99 ± 1.07) in the group treated with 4.0 mg/mL Angelica sinensis polysaccharide extract compared with the control group (58.38 ± 5.63; p < .05). In vivo, after treatment with ethylene glycol for 28 days, urinary oxidative stress, oxalate, creatinine, urea and urolithiasis-related protein were significantly increased (p < .05), except for serum oxidative stress (p > .05). The rats administered the extract of Angelica sinensis polysaccharide showed significantly decreased pathological change and CaOx deposition (p < .05) compared with the urolithiatic rats. Significantly reduced levels of urinary oxidative stress, oxalate, creatinine, urea and urolithiasis-related protein were observed in the Angelica sinensis polysaccharide treatment groups (p < .05) compared with the nephrolithic rats. CONCLUSION: The results presented here suggest that Angelica sinensis polysaccharide has the potential to inhibit CaOx crystallization in vitro and may present anti-urolithiatic effects in vivo.

Anti-Inflammatory and Anti-Urolithiasis Effects of Polyphenolic Compounds from Quercus gilva Blume.

Quercus gilva Bume (QGB, family Fagaceae) is a tall evergreen oak species tree that grows in warm temperate regions in Korea, Japan, China and Taiwan. Quercus plants have long been the basis of traditional medicines. Their clinical benefits according to traditional medicine include relief of urolithiasis, tremors and inflammation. In the present study, the anti-urolithiasis activity including anti-inflammatory and anti-oxidative activities, of some phenolic compounds isolated from QGB were described. Seven compounds were isolated and identified as picraquassioside D (1), quercussioside (2), (+)-lyoniresinol-9'α-O-ß-d-xylopyranoside (3), (+)-catechin (4), (-)-epicatechin (5), procyanidin B-3 (6), and procyanidin B-4 (7). Compounds 5-7 showed potent anti-oxidative and anti-inflammatory activities. These compounds were further tested for their inhibition of the gene expression of the inflammatory cytokines. The three compounds 5-7 showed dose-dependent inhibitory activities on gene expression of COX-2 and IL-1ß. In vivo, urolithiasis was induced more effectively in an animal model of acute urolithiasis by the administration of QGB extract. These results indicate the potential of compounds from QGB in the treatment of urolithiasis.

Antilithiatic effects of crocin on ethylene glycol-induced lithiasis in rats.

In this study, the antilithiatic potential of crocin, a pharmacologically active constituent of Crocus sativus L. (saffron), was evaluated against ethylene glycol (EG)-induced nephrolithiasis in rats. Negative control rats were provided with EG (1 %) in drinking water for 30 days. crocin (10, 20 and 40 mg/kg, i.p.) was administered simultaneously once daily for 30 days (prophylactic regimen) or 14 days after stone induction (therapeutic study). For biochemical analysis, 24-h urine was collected from all experimental animals at the beginning (day 0) and end of the experiment (day 30). The urine output was evaluated during the first 24 h (day 1). Ethylene glycol feeding resulted in decreased hyperoxaluria (P < 0.01) and total protein loss (P < 0.001), along with decreased excretion of citrate and magnesium (P < 0.01) compared with the intact animals. Treatment with prophylactic regimen of crocin (20 and 40 mg/kg) significantly reduced the elevated oxalate, and increased the citrate and magnesium levels of urine. The attenuation of protein loss was only seen with a high dose of crocin in a prophylactic study. Urine volume was not significantly altered after EG or crocin administration. The increased number of calcium deposits in the kidney tissue of lithiatic rats was decreased after prophylactic treatment with 20 and 40 mg/kg of crocin. The urinary ionic parameters and crystal count were not significantly altered after the therapeutic study. A marked increase in malondialdehyde (MDA, a lipid peroxidation product) level was observed in the EG-given group. Treatment with crocin (20 and 40 mg/kg) reduced the elevated levels of MDA. Results indicate that crocin can be effective in preventing urine calculi formation and recurrence of the disease. The mechanism underlying this effect is mediated possibly through balancing promoter and inhibitor factors and an antioxidant effect.

Non-drug-induced nephrotoxicity.

Several drugs and other compounds can induce acute and/or chronic nephrotoxicity. The goal of this study was to review clinical features of nephrotoxicity induced by 'atypical' or 'unconventional' agents, such as environmental agents (metals, minerals, animals), food agents (mushrooms, aristolochic acid, medicinal traditional herbals, dietary supplements, melamine), drugs, and other products (ethylene glycol). Nephrotoxicity varies according to local background, dependent on different food and cultural customs, as well as to differences in local fauna and flora. The incidence of such a phenomenon is not well known. Many different pathophysiological pathways are involved, and the spectrum of renal lesions is rather wide. 'Epidemic nephrotoxicity' may occur, as recently illustrated by the melamine epidemics in Chinese infants receiving powdered milk formulas; a rapid reaction to unusual increased frequency of acute kidney injury and nephrolithiasis in young children has led to a rapid analysis from international experts, with subsequent recommendations for diagnosis and care. Nephrotoxicity should be considered when there is any unexplained renal impairment, especially in children.

The effect of oculo-acupuncture on recovery from ethylene glycol-induced acute renal injury in dogs.

The potential recovery effect by oculo-acupuncture (OA) on ethylene glycol-induced acute renal injury in dogs was investigated. Acute renal damage was induced by ingestion of ethylene glycol in six mongrel dogs. The dogs were assigned to control (three dogs) and experimental (three dogs) groups. The control group did not receive any treatment, while the experimental group was treated with oculo-acupuncture at kidney/urinary bladder region plus zhong jiao region of the eyes after the induction of renal damage. Serum blood urea nitrogen (BUN), creatinine, sodium (Na), chloride (Cl), and potassium (K) were measured in both control and experimental groups. The blood RBC and Hb were also examined. The serum BUN and creatinine activities in the experimental group were lower than those in the control group, the serum Na and Cl had the irregular change in both groups, and the blood Hb in the control and experimental group showed decreasing tendency. Significant differences were observed on the 3rd and 7th day in BUN, 7th day in creatinine, 2nd day in Na and Cl, and 7th day in Hb when compared to the control group. Whereas, serum K concentration and RBC in the experimental group did not change significantly. The recovery findings of the renal injury were also observed in the experimental group histopathologically. In conclusion, OA therapy (kidney/urinary bladder region plus zhong jiao region) was effective for recovery of the renal injury induced by ethylene glycol in dogs.

A comparative study on several models of experimental renal calcium oxalate stones formation in rats.

In order to compare the effects of several experimental renal calcium oxalate stones formation models in rats and to find a simple and convenient model with significant effect of calcium oxalate crystals deposition in the kidney, several rat models of renal calcium oxalate stones formation were induced by some crystal-inducing drugs (CID) including ethylene glycol (EG), ammonium chloride (AC), vitamin D(3)[1alpha(OH)VitD(3), alfacalcidol], calcium gluconate, ammonium oxalate, gentamicin sulfate, L-hydroxyproline. The rats were fed with drugs given singly or unitedly. At the end of experiment, 24-h urines were collected and the serum creatinine (Cr), blood urea nitrogen (BUN), the extents of calcium oxalate crystal deposition in the renal tissue, urinary calcium and oxalate excretion were measured. The serum Cr levels in the stone-forming groups were significantly higher than those in the control group except for the group EG+L-hydroxyproline, group calcium gluconate and group oxalate. Blood BUN concentration was significantly higher in rats fed with CID than that in control group except for group EG+L-hydroxyproline and group ammonium oxalate plus calcium gluconate. In the group of rats administered with EG plus Vitamin D(3), the deposition of calcium oxalate crystal in the renal tissue and urinary calcium excretion were significantly greater than other model groups. The effect of the model induced by EG plus AC was similar to that in the group induced by EG plus Vitamin D(3). EG plus Vitamin D(3) or EG plus AC could stably and significantly induced the rat model of renal calcium oxalate stones formation.