Structural and Functional Modification of THP on Nitration: Comparison with Stone Formers THP

Viswanathan, Pragasam; Kalaiselvi, Periandavan; Subashini, Balasubramanian; Sumitra, Kamalanathan; Varalakshmi, P.

doi:10.1159/000081800

Cited by 15 publications

(14 citation statements)

References 66 publications

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“…Coadministration of EG and AC in rats showed increased levels of phosphate and oxalate in urine and kidney homogenate, suggesting selective accumulation of these ions into renal parenchyma. Similar results have been observed in previously reported studies [24,25].…”

Section: Discussionsupporting

confidence: 93%

“…Similar observations have been reported by researchers [24,25]. Literature survey suggests that various acidic metabolites such as hippuric acid, oxalic acid, formic acid, and benzoic acids are formed on EG metabolism causing metabolic acidosis.…”

Section: Discussionsupporting

confidence: 87%

“…The observed abnormal changes in the serum parameters [24,25]. Supplementation with MLG 400, GC 100, and GC 200 caused a marked reduction in serum BUN, creatinine, and uric acid.…”

Section: Discussionmentioning

confidence: 88%

“…The cellular injuries favor the adherence and retention CaOx crystals in renal tubules [38]. In addition, researchers have demonstrated two-fold increase in xanthine oxidase in oxidative stress and subsequent renal damage in EG-administered rats [25]. A significant decrease in SOD and CAT activity in kidney homogenate was observed in lithiatic rats.…”

Section: Discussionmentioning

confidence: 98%

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Protective effect of magnesium lactate gluconate and Garcinia cambogia fruit extract in experimentally induced renal calculi in rats

Kyada¹,

Mansuri²,

Patel³

2017

J Intercult Ethnopharmacol

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Aim: Antiurolithiatic activity of magnesium lactate gluconate (MLG) and aqueous extract of Garcinia cambogia (GC) fruit was studied. Materials and Methods: The study was performed during December 2016 to April 2017. Urolithiasis was induced in male Wistar rats by administration of 0.75% v/v ethylene glycol for 21 days. From 8 th day onward, intervention with MLG (200 and 400 mg/kg b.w.) and GC (100 and 200 mg/kg b.w.) was started. At the end of the treatment period, biochemical parameters affecting renal stone formation were estimated in the serum, urine, kidney homogenate, and histopathology of harvested kidneys was performed. Results: From in vivo evaluation, it was observed that MLG 400 mg/kg b.w., GC 100 mg/kg b.w., and GC 200 mg/kg b.w. significantly reduced nitrogenous waste products in serum (blood urea nitrogen, creatinine, and uric acid) as well as calculogenic promoters in urine (phosphate and oxalate) and kidney homogenate (calcium, phosphate, and oxalate) when compared to disease control animals. The MLG 200 and MLG 400 were ineffective in restoring superoxide dismutase (SOD) and catalase (CAT) enzyme activity, whereas GC 100, GC 200, and Cystone ® 400 mg/kg b.w. significantly elevated SOD and CAT enzymes in urolithiatic rat kidney. Conclusions: MLG and GC extracts are capable of preventing calcium oxalate (CaOx) crystal formation and subsequent deposition in renal tubules. The principle mechanism underlying nephroprotective effect of test drugs might be attributed to their calcium ion chelating ability and CaOx crystallization inhibitory activity. It is further asserted that GC was more potent than MLG in overall kidney protection by virtue of its antioxidant potential.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 87%

“…The observed abnormal changes in the serum parameters [24,25]. Supplementation with MLG 400, GC 100, and GC 200 caused a marked reduction in serum BUN, creatinine, and uric acid.…”

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 98%

See 2 more Smart Citations

Protective effect of magnesium lactate gluconate and Garcinia cambogia fruit extract in experimentally induced renal calculi in rats

Kyada¹,

Mansuri²,

Patel³

2017

J Intercult Ethnopharmacol

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“…The fact that the majority of renal stones recur and a significant subset of patients have family history further points to the possibility of a common physiological defect in nephrolithiasis (17). There is a range of pathophysiological conditions that can affect the expression or structure of OPN and THP in humans (4,11,15,16,33,34). It will be of particular interest and importance to define whether some of these molecular alterations, either quantitatively or qualitatively, contribute to the pathogenesis of human renal stones.…”

Section: Discussionmentioning

confidence: 99%

Renal calcinosis and stone formation in mice lacking osteopontin, Tamm-Horsfall protein, or both

Liaw

Evan³

et al. 2007

American Journal of Physiology-Renal Physiology

109

103

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Although often supersaturated with mineral salts such as calcium phosphate and calcium oxalate, normal urine possesses an innate ability to keep them from forming harmful crystals. This inhibitory activity has been attributed to the presence of urinary macromolecules, although controversies abound regarding their role, or lack thereof, in preventing renal mineralization. Here, we show that 10% of the mice lacking osteopontin (OPN) and 14.3% of the mice lacking Tamm-Horsfall protein (THP) spontaneously form interstitial deposits of calcium phosphate within the renal papillae, events never seen in wild-type mice. Lack of both proteins causes renal crystallization in 39.3% of the double-null mice. Urinalysis revealed elevated concentrations of urine phosphorus and brushite (calcium phosphate) supersaturation in THP-null and OPN/ THP-double null mice, suggesting that impaired phosphorus handling may be linked to interstitial papillary calcinosis in THP-but not in OPN-null mice. In contrast, experimentally induced hyperoxaluria provokes widespread intratubular calcium oxalate crystallization and stone formation in OPN/THP-double null mice, while completely sparing the wild-type controls. Whole urine from OPN-, THP-, or double-null mice all possessed a dramatically reduced ability to inhibit the adhesion of calcium oxalate monohydrate crystals to renal epithelial cells. These data establish OPN and THP as powerful and functionally synergistic inhibitors of calcium phosphate and calcium oxalate crystallization in vivo and suggest that defects in either molecule may contribute to renal calcinosis and stone formation, an exceedingly common condition that afflicts up to 12% males and 5% females. kidney stone; urolithiasis; uromodulin CLINICAL KIDNEY STONE DISEASE is classified into a number of forms, each requiring a specific plan for medical treatment. It has only been recently demonstrated through a series of biopsy studies of renal papillae from human stone formers that the different stones can develop through different pathways (7,13). Whether the pathogenetic process leading to stone formation involves interstitial plaque or intratubular crystal deposits, a range of host factors appears to be involved, some acting as facilitators and others as inhibitors. Under normal conditions, there is a fine equilibrium between pro-and anticrystallization forces, which helps keep the kidneys stone-free so that they can carry out important physiological functions. However, when the equilibrium breaks down, urine constituents can precipitate out, allowing insoluble crystals to form. Although the mechanisms that mediate retention of urinary crystals into stones remain poorly defined, it is clear that the degree of urinary supersaturation predicts stone risk and type (24,28,38). Furthermore, the urine of most individuals is frequently supersaturated with calcium oxalate and calcium phosphate. These observations suggest a critical role for urinary supersaturation and inhibitors of crystallization. This paradigm of nephrolithiasis has ...

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Detection of endothelial nitric oxide synthase and NADPH-diaphorase in experimentally induced hyperoxaluric animals

et al. 2005

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Nitrosative stress plays a role in calcium oxalate stone formation, as nitrosated proteins have been identified in stone formers. Nitric oxide (NO(*)), the common precursor for reactive nitrogen species, is synthesized in the juxtaglomerular apparatus of the kidneys. The present study is aimed to determine the role of nitric oxide synthase (NOS) in an experimental hyperoxaluric condition by histological and biochemical techniques. Hyperoxaluria was induced by 0.75% ethylene glycol in drinking water. L-arginine (L-arg) was supplemented at a dose of 1.25 g/kg body weight orally for 28 days. Nitric oxide metabolites (NOx), protein content in the urine and lipid peroxidation in the kidney were determined at the end of the experimental period. Histopathological examination of the rat kidneys was then carried out. NADPH-diaphorase and eNOS expression studies were carried out in control and hyperoxaluric rat kidneys using histochemical and immunohistochemical techniques. Significant amounts of NOx were present in the urine of hyperoxaluric animals when compared to control rats. Histopathological examinations revealed membrane injury, tubular dilatation and edema in the hyperoxaluric rats, whereas co-supplementation of L-arg to the hyperoxaluric rats significantly reduced these changes. The results of histochemical analysis for NADPH-diaphorase staining demonstrate the role of NOS in hyperoxaluric rats. Hyperoxaluric rats showed intense staining for NADPH-diaphorase when compared to control and L-arg co-supplemented hyperoxaluric rats. Immunohistochemical demonstration confirmed that eNOS expression was markedly increased in L-arg supplemented rats, when compared to EG treated rat kidney sections. Thus, from the present study, we conclude that supplementation of L-arg to the hyperoxaluric animals minimizes the cellular injury mediated by ethylene glycol, prevents oxidative/nitrosative damage to the membranes and reduces the incidence of calcium oxalate stone formation.

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Structural and Functional Modification of THP on Nitration: Comparison with Stone Formers THP

Cited by 15 publications

References 66 publications

Protective effect of magnesium lactate gluconate and Garcinia cambogia fruit extract in experimentally induced renal calculi in rats

Protective effect of magnesium lactate gluconate and Garcinia cambogia fruit extract in experimentally induced renal calculi in rats

Renal calcinosis and stone formation in mice lacking osteopontin, Tamm-Horsfall protein, or both

Detection of endothelial nitric oxide synthase and NADPH-diaphorase in experimentally induced hyperoxaluric animals

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