SALUBRIOUS EFFECT OF ROTTLERIN ON HYPEROXALURIA INDUCED OXIDATIVE DAMAGE IN RATS

Objective: To investigate the in vitro oxidant scavenging properties of rottlerin and to study the potential role of rottlerin on ethylene glycol induced nephrocalcinosis in rats.Methods: In vitro oxidant scavenging properties of rottlerin were studied along with its effect on in vitro calcium phosphate mineralization. For the in vivo studies, hyperoxaluria was induced by administering 0.4 % ethylene glycol and 1 % ammonium chloride in drinking water to male wistar rats for 9 d. Rottlerin was administered intraperitoneally at 1mg/kg/d along with the hyperoxaluric agent. Total thiols content, activities of glutathione-S-transferase (GST), glutathione reductase (GR), Citrate synthase (CS), isocitrate dehydrogenase (ICDH), ATPase and urinary parameters were studied.Results: Rottlerin showed in vitro DPPH, superoxide, and ABTS radical scavenging activity along with inhibition of calcium phosphate mineralization in an in vitro homogeneous system. The diminished activities of GST, GR, ICDH, CS, ATPase and level of total thiols were considerably stabilized by rottlerin, suggesting that rottlerin provides protection against oxalate induced oxidative damage.Conclusion: We suggest that rottlerin protects the integrity of the renal cell by stabilizing the free-radical mediated damage. Thus, the present study reveals that the antioxidant nature of rottlerin protects the renal cells against oxalate-induced injury and thus, rottlerin may prevent against hyperoxaluria induced oxidative damage.Keywords: Rottlerin, Hyperoxaluria, Oxidative stress, Antioxidan

On twisted group ring isomorphism problem for p-groups

In this article, we explore the problem of determining isomorphisms between the twisted complex group algebras of finite $p$-groups. This problem bears similarity to the classical group algebra isomorphism problem and has been recently examined by Margolis-Schnabel. Our focus lies on a specific invariant, referred to as the generalized corank, which relates to the twisted complex group algebra isomorphism problem. We provide a solution for non-abelian $p$-groups with generalized corank at most three

THE ROLE OF NATURAL ANTIOXIDANTS AS POTENTIAL THERAPEUTIC AGENT IN NEPHROLITHIASIS

Renal injury and inflammation caused by ROS play a major role in stone formation. Under the hyperoxaluric condition, crystal deposition results in angiotensin II (Ang II) activation. NADPH Oxidase is stimulated by activated Ang II, leading to ROS production, which can damage renal cells. Oxidative stress also results in mitochondrial dysfunction and release of pro-apoptotic factors from depolarized mitochondria that result in apoptosis that leads to renal injury. Crystal retention in the kidney requires tubular epithelial injury accompanied by luminal expression of HA, OPN, and CD44. The expression of these molecules turns a non–crystal-binding epithelium into a crystal-binding one, thereby setting the stage for crystal retention. Recently many antioxidants have been studied that prevent hyperoxaluria mediated nephrolithiasis. Antioxidant treatment significantly reduces CaOx crystal deposition in kidneys. Naturally occurring antioxidants such as Vitamin E, Apocynin, Phycocyanin, Fucoidin, Gallotannins, Rottlerin, Lupeol, Curcumin, etc. have shown significant effect in combating renal injury which is an early event in nephrolithiasis. These findings point towards a great potential for the therapeutic application of antioxidants and free radical scavengers to reduce stone occurrence particularly under hyperoxaluric conditions. This review article attempts to compile various naturally occurring antioxidants used in treatment of nephrolithiasis. Keywords: Calcium oxalate, Oxidative stress, Hyperoxaluria, Reactive oxygen species, antioxidant

Preventive and curative effects of<i style=""> Achyranthes aspera</i> Linn. extract in experimentally induced nephrolithiasis

201-208The present study was undertaken to evaluate the efficacy of Achyranthes aspera in preventing and reducing the growth of calcium oxalate stones in ethylene glycol induced nephrolithiatic model. Hyperoxaluria was induced in rats using ethylene glycol (EG, 0.4%) and ammonium chloride (1%) for 15 days and was then replaced with EG (0.4%) only. Upon administration of cystone (750 mg/kg body wt.), aqueous extract of A. aspera (500 and 1000 mg/kg body wt.), levels of renal injury markers (lactate dehydrogenase and alkaline phosphatase) were normalized with a decrease in serum urea and serum creatinine. Concurrent treatment reduced changes in the architecture of renal tissue and also decreased the size of crystals thereby helping in quick expulsion of the crystals. The present results indicated that Achyranthes aspera had an ability to maintain renal functioning and reduced renal injury

Effect of Oxytetracycline on In vitro Mineralization and Demineralization Reactions in the Absence and Presence of Collagen

Introduction: Oxytetracycline and its derivatives are routinely used to treat various ailments have also been shown to inhibit embryonic bone formation, mineralization in pregnant female rats and parathyroid hormone induced demineralization of bones. Oxytetracycline has also been routinely used as bone fluorochrome to study bone metabolism. However, despite the above observations, its mechanism of action is not clearly understood. Some studies tend to suggest that it acts by inhibiting collagen biosynthesis while others indicate that it acts without influencing collagen metabolism. Aim: To study the mechanism by which oxytetracycline influences the mineralization and demineralization reactions. Materials and Methods: Homogeneous and heterogeneous systems of in vitro mineralization under physiological conditions of temperature, pH and ionic strength were used to investigate the effect of oxytetracycline not only on initial mineral phase formation but also on its subsequent growth or demineralization. In the Homogenous system, supersaturated conditions with respect to calcium and phosphate ions were employed to study their precipitation as mineral phase resembling hydroxyapatite in nature. However, in the heterogeneous system, collagen isolated from sheep tendons was used to induce identical mineral phases under saturated conditions with respect to calcium and phosphate ions prevailing in the body fluids. Results: The study demonstrated that in the homogeneous reaction system (mineralization in the absence of collagen) oxytetracycline inhibited both the initial mineral phase formation and its subsequent growth without influencing its demineralization. However, in the heterogeneous system, oxytetracycline was found to inhibit not only the initial mineralization but also its subsequent growth or demineralization. Conclusion: Oxytetracycline acted like crystal poisons to inhibit the mineralization and demineralization reactions by tightly associating with the mineral phase

Association of the Wild-Type A/A Genotype of MBL2 Codon 54 with Asthma in a North Indian Population

Background: High serumMBL level as well as polymorphisms in the mannose-binding lectin 2 (MBL2) gene resulting in MBL deficiency are involved in the mechanism of a number of non-infectious diseases such as asthma, conferring either risk or protection in different population studies. MBL being the first reactant of the MBL pathway is also a major determinant of the fate of the anaphylatoxins such as C3a and C5a, which are also pro-inflammatory mediators. The MBL2 gene polymorphisms thus control the serum levels of MBL as well as C3a and C5a

The Restrained Expression of NF-kB in Renal Tissue Ameliorates Folic Acid Induced Acute Kidney Injury in Mice

<div><p>The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI), which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA) induced acute kidney injury (AKI) characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI). Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC) lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI.</p></div

Mouse mRNA primers for RT-PCR.

<p>Mouse mRNA primers for RT-PCR.</p

Recovery of renal function on treatment with PDTC.

<p>The level of serum creatinine was measured at 12 hr (A) and 48 hr (B) after single i.p. injection of FA. PDTC was administered 2 hr before FA treatment. Data are presented as mean ±SEM (N = 6 animals per group). *P<0.05 compared between control and FA treated groups. #P<0.05 compared between FA treated group and FA+PDTC treated group. Magnification: 400X, scale bar: 100 µm.</p

Effects of PDTC on renal genes expression after FA induced injury in mice.

<p>The mRNA expression of p65 (B), nf-kb2 (C), and p53 (D), was measured at 12 hours after injection of FA+vehicle or FA+PDTC byRT-PCR. The mRNA levels were normalized by the expression of GAPDH in each experiment, and were expressed as % fold change relative to control animals. Data are presented as mean ±SEM (N = 3 animals per group). *P<0.05 compared between control and FA treated group. #P<0.05 compared between FA treated group and FA+PDTC treated group.</p