Elimination Of Toxins Research Articles

Medicinal plants used in preparation of polyherbal ayurvedic formulation Chyawanprash

Chyawanprash has been used traditionally in Ayurvedic supplements to help strengthen your digestive system and promote food absorption, corrects hyperacidity, dyspepsia and flatulence, peptic ulcers and gastritis, boost memory power, promote cardio fitness by supporting your heart and helps in slow down the rate of normal aging and promote longevity. It also cleanse your blood and aid in the elimination of toxins, rejuvenate and promote a healthy-looking complexion, support healthy bones and teeth through calcium absorption, help tone your muscles through protein synthesis, provide relief from occasional menstrual discomfort and boost your immune system to improve vigor, vitality, wisdom, and glow. But nowadays many pharmaceutical and herbal companies deviate from the original formula given in ayurveda. This review highlights on the details of different Indian medicinal plants used in the preparation of chyawanprash and their composition and formula, followed in ancient ayurveda. Key words: Chyawanprash, polyherbal formulation, medicinal plants in chawanprash, herbal supplements.

Ca2+ Influx and Tyrosine Kinases Trigger Bordetella Adenylate Cyclase Toxin (ACT) Endocytosis. Cell Physiology and Expression of the CD11b/CD18 Integrin Major Determinants of the Entry Route

Humans infected with Bordetella pertussis, the whooping cough bacterium, show evidences of impaired host defenses. This pathogenic bacterium produces a unique adenylate cyclase toxin (ACT) which enters human phagocytes and catalyzes the unregulated formation of cAMP, hampering important bactericidal functions of these immune cells that eventually cause cell death by apoptosis and/or necrosis. Additionally, ACT permeabilizes cells through pore formation in the target cell membrane. Recently, we demonstrated that ACT is internalised into macrophages together with other membrane components, such as the integrin CD11b/CD18 (CR3), its receptor in these immune cells, and GM1. The goal of this study was to determine whether ACT uptake is restricted to receptor-bearing macrophages or on the contrary may also take place into cells devoid of receptor and gain more insights on the signalling involved. Here, we show that ACT is rapidly eliminated from the cell membrane of either CR3-positive as negative cells, though through different entry routes, which depends in part, on the target cell physiology and characteristics. ACT-induced Ca2+ influx and activation of non-receptor Tyr kinases into the target cell appear to be common master denominators in the different endocytic strategies activated by this toxin. Very importantly, we show that, upon incubation with ACT, target cells are capable of repairing the cell membrane, which suggests the mounting of an anti-toxin cell repair-response, very likely involving the toxin elimination from the cell surface.

The glutathione S-transferase T1 deletion is associated with susceptibility to multiple sclerosis

BackgroundMultiple sclerosis (MS) occurs as a result of interaction between genetic and environmental factors. Recent data support the view that oxidative damage is one of an early event in MS tissue injury. The safe elimination of reactive oxygen species and toxins via glutathione S-transferase (GST) pathways is required in order to protect cells against reactive oxygen-induced damage. The aim of our study was to analyze the possible association of GSTM1 and GSTT1 gene polymorphisms with the susceptibility and clinical parameters of MS, in 455 consecutive patients and 366 controls. MethodsA multiplex polymerase chain reaction (PCR) was used to detect the deletions in GSTM1 and GSTT1 genes. ResultsPatients with MS had significantly higher frequency of GSTT1 null genotype compared to controls (37.36% vs. 21.86%, respectively, p<0.0001, adjusted OR 2.13 (1.56–2.90)), as well as double deletions (15.38% vs. 10.38%, respectively, p<0.05). The carriers of GSTM1 deletion had significantly earlier onset of MS compared to the wild-type carriers (28.31±8.45 vs. 30.64±9.30years, respectively, p=0.03). ConclusionThis study suggests the potential pathogenic role of GSTT1 deletion on MS susceptibility. There are no similar data published so far, yet this study should be replicated in other populations.

Mathematical modeling of kidney transport

In addition to metabolic waste and toxin excretion, the kidney also plays an indispensable role in regulating the balance of water, electrolytes, nitrogen, and acid-base. In this review, we describe representative mathematical models that have been developed to better understand kidney physiology and pathophysiology, including the regulation of glomerular filtration, the regulation of renal blood flow by means of the tubuloglomerular feedback mechanisms and of the myogenic mechanism, the urine concentrating mechanism, epithelial transport, and regulation of renal oxygen transport. We discuss the extent to which these modeling efforts have expanded our understanding of renal function in both health and disease.

Indoxyl Sulfate Down-Regulates SLCO4C1 Transporter through Up-Regulation of GATA3

The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. However, the precise mechanism of the nephrotoxicity of uremic toxins on renal transport has been poorly understood. Here we report that indoxyl sulfate, one of the potent uremic toxins, directly suppresses the renal-specific organic anion transporter SLCO4C1 expression through a transcription factor GATA3. The promoter region of SLCO4C1 gene has several GATA motifs, and indoxyl sulfate up-regulated GATA3 mRNA and subsequently down-regulated SLCO4C1 mRNA. Overexpression of GATA3 significantly reduced SLCO4C1 expression, and silencing of GATA3 increased SLCO4C1 expression vice versa. Administration of indoxyl sulfate in rats reduced renal expression of slco4c1 and under this condition, plasma level of guanidinosuccinate, one of the preferable substrates of slco4c1, was significantly increased without changing plasma creatinine. Furthermore, in 5/6 nephrectomized rats, treatment with oral adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and conversely increased the expression of slco4c1, following the reduction of plasma level of guanidinosuccinate. These data suggest that the removal of indoxyl sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated renal excretion of uremic toxins in CKD.

Adult sea lamprey tolerates biliary atresia by altering bile salt composition and renal excretion.

The sea lamprey (Petromyzon marinus) is a genetically programmed animal model for biliary atresia, as it loses its bile ducts and gallbladder during metamorphosis. However, in contrast to patients with biliary atresia or other forms of cholestasis who develop progressive disease, the postmetamorphosis lampreys grow normally to adult size. To understand how the adult lamprey thrives without the ability to secrete bile, we examined bile salt homeostasis in larval and adult lampreys. Adult livers were severely cholestatic, with levels of bile salts >1 mM, but no evidence of necrosis, fibrosis, or inflammation. Interestingly, both larvae and adults had normal plasma levels (∼10 μM) of bile salts. In larvae, petromyzonol sulfate (PZS) was the predominant bile salt, whereas the major bile salts in adult liver were sulfated C27 bile alcohols. Cytotoxicity assays revealed that PZS was highly toxic. Pharmacokinetic studies in free-swimming adults revealed that ∼35% of intravenously injected bromosulfophthalein (BSP) was eliminated over a 72-hour period. Collection of urine and feces demonstrated that both endogenous and exogenous organic anions, including biliverdin, bile salts, and BSP, were predominantly excreted by way of the kidney, with minor amounts also detected in feces. Gene expression analysis detected marked up-regulation of orthologs of known organic anion and bile salt transporters in the kidney, with lesser effects in the intestine and gills in adults compared to larvae. These findings indicate that adult lampreys tolerate cholestasis by altering hepatic bile salt composition, while maintaining normal plasma bile salt levels predominantly through renal excretion of bile products. Therefore, we conclude that strategies to accelerate renal excretion of bile salt and other toxins should be beneficial for patients with cholestasis. (HEPATOLOGY 2013;57:2418-2426).

JBP485 improves gentamicin-induced acute renal failure by regulating the expression and function of Oat1 and Oat3 in rats

We investigated the effects of JBP485 (an anti-inflammatory dipeptide and a substrate of OAT) on regulation of the expression and function of renal Oat1 and Oat3, which can accelerate the excretion of accumulated uremic toxins (e.g. indoxyl sulfate) in the kidney to improve gentamicin-induced ARF in rats. JBP485 caused a significant decrease in the accumulation of endogenous substances (creatinine, blood urea nitrogen and indoxyl sulfate) in vivo, an increase in the excretion of exogenous compounds (lisinopril and inulin) into urine, and up-regulation of the expressions of renal Oat1 and Oat3 in the kidney tissues and slices via substrate induction. To determine the effect of JBP485 on the accelerated excretion of uremic toxins mediated by Oat1 and Oat3, the mRNA and protein expression levels of renal basolateral Oats were assessed by quantitative real-time PCR, western blot, immunohistochemical analysis and an immunofluorescence method. Gentamicin down-regulated the expression of Oats mRNA and protein in rat kidney, and these effects were reversed after administration of JBP485. In addition, JBP485 caused a significant decrease in MPO and MDA levels in the kidney, and improved the pathological condition of rat kidney. These results indicated that JBP485 improved acute renal failure by increasing the expression and function of Oat1 and Oat3, and by decreasing overoxidation of the kidney in gentamicin-induced ARF rats.

Temperature effects on kinetics of paralytic shellfish toxin elimination in Atlantic surfclams, Spisula solidissima

Surfclams, Spisula solidissima, pose a particular health risk for human consumption as they are characterized by accumulation of extremely high levels of toxins associated with paralytic shellfish poisoning (PSP), slow toxin elimination and an extremely high post-ingestive capacity for toxin bioconversion. Surfclam populations experience a wide range of temperatures along the NW Atlantic continental shelf, and are undergoing range contraction that has been attributed to global warming. In this study the influence of temperature (5, 12 and 21°C) on detoxification kinetics of individual PSP toxins in two tissue compartments of juvenile surfclams (∼35mm shell length) was determined under controlled laboratory conditions, over prolonged (2.4 months) depuration. Clams were toxified with a representative regional Gulf of Maine isolate of the dinoflagellate Alexandrium fundyense of known toxin profile, allowing tracking of changes in toxin composition and calculated toxicity in surfclam tissues. The visceral mass detoxified at all temperatures, although toxin loss rate increased with increasing temperature. In contrast, total toxin content and calculated toxicities in other tissues remained constant or even increased during depuration, suggesting a physiological or biochemical toxin-retention mechanism in this tissue pool and temperature-independent detoxification. In vivo toxin compositional changes in surfclam tissues found in this study provide evidence of specific toxin conversion pathways, involving both reductive and decarbamoylation pathways. We conclude that such toxin biotransformations, especially in non-visceral tissues, may introduce a discrepancy in describing kinetics of total toxicity (in saxitoxin equivalents [STXeq]) of S. solidissima over prolonged detoxification. Nevertheless, use of total toxicity values generated by routine regulatory monitoring based upon mouse bioassays or calculated from chemical analytical determination of molar toxin concentrations is adequate for first-order modeling of toxin kinetics in this species. Furthermore, the differential detoxification response of viscera and other tissues in relation to temperature emphasizes the need for two-compartment modeling to describe the fate of PSP toxins in this species. Finally, key parameters were identified that may prove useful in hindcasting the timing of toxic blooms or new toxin input in deep offshore waters where routine monitoring of toxic phytoplankton is impractical.

Water Treatment through Chemical Transformation and Elimination of Organic Toxin Based on Mesoporous Nickel Oxide Nanocrystals

The development of sustainable catalyst could potentially provide a long-term solution for the industrial process that required production of a large quantity of raw materials for the chemical industry from renewable resources. Hence, achieving proper designs of highly efficient, sustainable and long-term reusable catalyst is one of the environmentally crucial issues facing humanity. Here, we report the fabrication of mesoporous NiO nanocatalyst in different morphology via a simple hydrothermal method. The mesoporous NiO nanocatalysts exhibit high catalytic activity and fast removal of toxic chemical agents from aquatic life.

Colon may provide new therapeutic targets for treatment of chronic kidney disease with Chinese medicine

Chronic kidney disease (CKD) has become a worldwide health and social problem. Retarding its progression to end-stage renal disease is beneficial both to the patients and the healthcare system. Plenty of clinical trials have indicated that enema with Chinese medicine could effectively prevent chronic renal failure, and was widely used in the clinical practice. However, studies on mechanism were still nearly blank, which may prevent further improvement of therapeutic efficacy. Recent studies had discovered that colon was an important organ where uremic toxins were generated. The uremic toxins involved could not only promote CKD progression, but also was closely correlated with CKD mortality. Reducing production and promoting excretion of toxins were confirmed to reduce renal tubule interstitial fibrosis and delay renal progression. On the basis of the theory of gut-kidney axis above, we had conducted pilot clinical researches to evaluate the effect of enema with Chinese medicine on the intestinal flora, gut barrier, enterogenous uremic toxins and renal protection. The preliminary results revealed that rheum enema through colon could accelerate intestinal dynamics, improve intestinal barrier function, regulate intestinal flora and reduce production and absorption of intestine-derived uremic toxins such as indoxyl sulfate, which may reduce renal fibrosis and delay renal progression. Further studies could provide more evidence for colon as a new therapeutic target for the treatment of CKD with Chinese medicine.

Multi-adaptive neural-fuzzy system as a novel predictor of in-vivo blood side dialyser urea clearance

The blood urea concentration has been used as a surrogate marker for toxin elimination in hemodialysed patients, and several indices based on it have been proposed in recent years for monitoring treatment adequacy. Measuring urea nitrogen concentrations at the inlet and outlet of dialyser is crucial to evaluate the in-vivo blood side dialyser urea clearance during hemodialysis. Although frequent measurement is needed to avoid inadequate dialysis efficiency, artificial intelligence can repeatedly perform the forecasting tasks and may be a satisfactory substitute for laboratory tests. Neuro-fuzzy technology represents a promising forecasting application in clinical medicine. In this study, two fuzzy models have been proposed to predict dialyser inlet and outlet urea concentrations in order to estimate dialyser clearance without blood sampling. The model is of multi-input single-output MISO type. Multi-adaptive neuro-fuzzy inference system MANFIS technique of fuzzy-based systems has been employed. The performance of the model is authenticated by evaluating the predicted results with the practical results obtained by conducting the confirmation experiments. The results suggest that the neuro-fuzzy technology, based on limited clinical parameters, is an excellent alternative method for accurately predicting arterial and venous urea concentrations in hemodialysis patients. The proposed model can be used for intelligent online adaptive system.

Green cocoons in silkworm Bombyx mori resulting from the quercetin 5-O-glucosyltransferase of UGT86, is an evolved response to dietary toxins

The glycosylation of UDP-glucosyltransferases (UGTs) is of great importance in the control and elimination of both endogenous and exogenous toxins. Bm-UGT10286 (UGT86) is the sole provider of UGT activity against the 5-O position of quercetin and directly influences the formation of green pigment in the Bombyx cocoon. To evaluate whether cocoon coloration evolved for mimetic purposes, we concentrated on the expression pattern of Ugt86 and the activities of the enzyme substrates. The expression of Ugt86 was not only detected in the cocoon absorbing and accumulating tissues such as the digestive tube and silk glands, but also in quantity in the detoxification tissues of the malpighian tubes and fat body, as well as in the gonads. As in the green cocoon strains, Ugt86 was clearly expressed in the yellow and white cocoon strains. In vitro, the fusion protein of UGT86 showed quercetin metabolic activity. Nevertheless, Ugt86 expression of 5th instar larvae was not up-regulated in the silk gland by exogenous quercetin. However, it was significantly up-regulated in the digestive tube and gonads (P < 0.05). A similar result was observed in experiments where larvae were exposed to rutin, an insect resistance inducer and growth inhibitor typically found in plants, and to 20-hydroxylecdysone (20E), an insect endocrine and plant source hormone. On the contrary, up-regulated Ugt86 expression was almost nil in larvae exposed to juvenile hormone III (P > 0.05). The results of HPLC revealed that a new substance was formed by mixing 20E with the recombinant UGT86 protein in vitro, indicating that the effect of Ugt86 on 20E was similar to that on exogenous quercetin derived from plant food, and that the effect probably initiated the detoxification reaction against rutin. The conclusion is that the reaction of Ugt86 on the silkworm cocoon pigment quercetin is not the result of active mimetic ecogenesis, but derives from the detoxification of UGTs.

N-glycosylation Dictates Proper Processing of Organic Anion Transporting Polypeptide 1B1

Organic anion transporting polypeptides (OATPs) have been extensively recognized as key determinants of absorption, distribution, metabolism and excretion (ADME) of various drugs, xenobiotics and toxins. Putative N-glycosylation sites located in the extracellular loops 2 and 5 is considered a common feature of all OATPs and some members have been demonstrated to be glycosylated proteins. However, experimental evidence is still lacking on how such a post-translational modification affect the transport activity of OATPs and which of the putative glycosylation sites are utilized in these transporter proteins. In the present study, we substituted asparagine residues that are possibly involved in N-glycosylation with glutamine residues and identified three glycosylation sites (Asn134, Asn503 and Asn516) within the structure of OATP1B1, an OATP member that is mainly expressed in the human liver. Our results showed that Asn134 and Asn516 are used for glycosylation under normal conditions; however, when Asn134 was mutagenized, an additional asparagine at position 503 is involved in the glycosylation process. Simultaneously replacement of all three asparagines with glutamines led to significantly reduced protein level as well as loss of transport activity. Further studies revealed that glycosylation affected stability of the transporter protein and the unglycosylated mutant was retained within endoplasmic reticulum.

Correlates of nonalcoholic fatty liver among women receiving residential mental health care

To review the risk factors for diagnosis of nonalcoholic fatty liver disease (NAFLD) in women in a mental health, dual diagnosis, treatment facility. A review of the literature and retrospective chart reviews of patients to identify factors within this population of women most closely associated with diagnosis of NAFLD. NAFLD is a common diagnosis and as obesity rates increase in the United States the incidence for this disease is also increasing. Identifiable risk factors are associated with the presence of this disease. Advanced practice nurses, as prescribers, need to be aware that the presence of NAFLD may interfere with drug metabolism and toxin elimination in their patients. Numerous physical conditions, behavioral symptoms, and laboratory findings are identified as associated conditions of NAFLD. Patients seen in primary care practices have NAFLD, but patients in treatment centers for mental health disorders are also affected. This population is particularly at risk because of the hepatotoxic effects of many medications used in psychiatric-mental health settings.

Changes in expression of renal Oat1, Oat3 and Mrp2 in cisplatin-induced acute renal failure after treatment of JBP485 in rats

The purpose of this study is to investigate whether the effect of cyclo-trans-4-l-hydroxyprolyl-l-serine (JBP485) on acute renal failure (ARF) induced by cisplatin is related to change in expression of renal Oat1, Oat3 and Mrp2 in rats. JBP485 reduced creatinine, blood urea nitrogen (BUN) and indoxyl sulfate (IS) in plasma and malondialdehyde (MDA) in kidney, and recovered the glomerular filtration rate (GFR) and the activity of superoxide dismutase (SOD) in cisplatin-treated rats. The plasma concentration of PAH (para-aminohippurate) determined by LC–MS/MS was increased markedly after intravenous administration of cisplatin, whereas cumulative urinary excretion of PAH and the uptake of PAH in kidney slices were significantly decreased. qRT-PCR and Western-blot showed a decrease in mRNA and protein of Oat1 and Oat3, an increase in mRNA and protein of Mrp2 in cisplatin-treated rats, and an increase in IS (a uremic toxin) after co-treatment with JBP485. It indicated that JBP485 promoted urinary excretion of toxins by upregulating renal Mrp2. This therefore gives in part the explanation about the mechanism by which JBP485 improves ARF induced by cisplatin in rats.

Modeling Transport and Flow Regulatory Mechanisms of the Kidney

The kidney plays an indispensable role in the regulation of whole-organism water balance, electrolyte balance, and acid-base balance, and in the excretion of metabolic wastes and toxins. In this paper, we review representative mathematical models that have been developed to better understand kidney physiology and pathophysiology, including the regulation of glomerular filtration, the regulation of renal blood flow by means of the tubuloglomerular feedback mechanisms and of the myogenic mechanism, the urine concentrating mechanism, and regulation of renal oxygen transport. We discuss how such modeling efforts have significantly expanded our understanding of renal function in both health and disease.

Low susceptibility of non-target Lepidopteran maize pests to the Bt protein Cry1Ab

Transgenic Bt maize expressing the Cry1Ab toxin is poorly effective for suppressing populations of two non-target Lepidoptera, Mythimna unipuncta and Helicoverpa armigera. In order to determine the mechanisms that may be involved in this poor effectiveness, last instar larvae of the two Lepidoptera were fed with a diet containing lyophilized leaves with Bt vs non-Bt toxin for different periods; additionally, some larvae fed on Bt diet were transferred to non-Bt diet for an additional period. In the experimental larvae, we measured the growth (weight) gain from just before treatment to after the end of the treatment, and the Cry1Ab contents in the hemolymph, the peritrophic membrane and its contents and midgut epithelium. Effects of the treatments on the midgut epithelium were observed by light and transmission electron microscopy. It was seen that multiple mechanisms can be involved in the low susceptibility of the two Lepidoptera. The low content of the toxin within the peritrophic membrane 48 h after ingestion indicates a high rate of toxin elimination in this space. Moreover, M. unipuncta larvae fed on the Bt diet displayed a similar growth gain index to those fed on the non-Bt diet, and showed an increasing elimination rate during the experiment. Little toxin reached the midgut epithelium, indicating a low permeability of the peritrophic membrane or a low affinity at the binding sites. Larvae fed on the Bt toxin showed rapid recovery in weight gain and in the midgut epithelium, and also showed overcompensation mechanisms.

Physiologie rénale

The kidneys are responsible for the urinary excretion of uremic toxins and the regulation of several body systems such as intra and extracellular volume status, acid-base status, calcium and phosphate metabolism or erythropoiesis. They adapt quantitative and qualitative composition of the urine to keep these systems in balance. The flow of plasma is filtered in the range of 120mL/min, and depends on the systemic and renal hemodynamics which is subject to self-regulation. The original urine will then be modified in successive segments of the nephron. The proximal nephron is to lead the massive reabsorption of water and essential elements such as sodium, bicarbonates, amino-acids and glucose. The distal nephron includes the distal convoluted tubule, the connector tube and the collecting duct. Its role is to adapt the quality composition of urine to the needs of the body.

Commentary on the burden of chronic kidney disease

The kidneys are two bean shaped organs situated in the abdomen that is responsible for the excretion of metabolic waste, production of hormones, and metabolism and excretion of drugs and toxins amongst others. Chronic renal failure is said to occur when there isan irreversible deterioration of kidney function, which develops over a period of years. This ultimately leads to end-stage renal failure at which stage kidney function must be replaced artificially by either renal dialysis or renal transplantation in order to avert death.&#x0D; The incidence and prevalence of kidney failure has been on the increase in recent times. The prevalence increased from 10% in 1988-1994 to 13.1% in 1999-2004. Kidney failure is also the ninth leading cause of death in the United States. In Nigeria, the data from various centres indicate an increasing incidence of kidney diseases in the population. The increase in kidney failure is partly explained by the rising incidence and prevalence of Diabetes and hypertension, the two leading causes of kidney failure. Other causes of kidney failure include glomerular disease, analgesic nephropathy, obstructive uropathy, chronic pyelonephritis, sickle cell disease amongst others.

Toxicology in the Emergency Department

General assessment, resuscitation strategies, and risk assessment of the poisoned patient are explored in this article, including specific interventions for unresponsive patients and seizures. Sympathomimetic and anticholinergic toxidromes are described in terms of clinical presentation and treatment strategies and are compared with other common toxidromes. Controversies in gastric decontamination are also outlined, including consensus panel and national organizational recommendations. Despite available methods for toxin elimination, advances in medicine, and pharmacotherapy options, the cornerstone of toxicology remains supportive care. The purpose of this article is to equip the advanced practice nurse in the emergency setting with baseline knowledge to provide initial care of the poisoned patient.