Evaluation of the water disinfection by-product dichloroacetonitrile-induced biochemical, oxidative, histopathological, and mitochondrial functional alterations: Subacute oral toxicity in rats

2017 ◽  
Vol 34 (3) ◽  
pp. 158-168 ◽  
Author(s):  
Ying Dong ◽  
Fang Li ◽  
Haijun Shen ◽  
Rongzhu Lu ◽  
Siqi Yin ◽  
...  
Keyword(s):  
Renal Damage ◽  
Water Disinfection ◽  
Retinol Binding Protein ◽  
Oral Exposure ◽  
Oral Toxicity ◽  
Vacuolar Degeneration ◽  
Hepatic Glutathione ◽  
Liver And Kidney ◽  
Renal Tubular ◽  
By Products

Dichloroacetonitrile (DCAN), an emerging nitrogenous disinfection by-product, is more genotoxic and cytotoxic than the currently regulated carbonaceous disinfection by-products such as haloacetic acids. Few mechanistic studies have been conducted on the hepatic and renal toxicities of DCAN. This study examined the clinical biochemical, hematological, histopathological, oxidative, and mitochondrial functional alterations to evaluate the systematic toxicity after subacute oral exposure of 11 or 44 mg/kg/day in rats for 28 days. Body and spleen weights were lower, and organ-to-body weight ratios of the liver and kidney were higher in rats administered 44-mg/kg DCAN than in controls. The activities of serum alanine aminotransferase and alkaline phosphatase, and concentrations of blood serum urea nitrogen and retinol-binding protein were increased in rats administered 44-mg/kg DCAN compared with those of controls, thereby indicating hepatic and renal damage in this group. This was confirmed by histopathological alterations, including hepatic sinus dilation, extensive hemorrhage, vacuolar degeneration in the liver and glomerulus hemorrhage, and renal tubular swelling, in DCAN-exposed rats. Exposure to 44-mg/kg DCAN induced hepatic oxidative damage shown by the significant increase in malonaldehyde levels, a poisonous product of lipid peroxidation. Exposure to 44-mg/kg DCAN significantly increased hepatic glutathione content and mitochondrial bioenergy as noted by the elevation of mitochondrial membrane potential and cytochrome c oxidase activity, which might be attributed to compensatory pathophysiologic responses to DCAN-induced hepatic mitochondrial damage.

Retinol Binding Proteinuria and Phosphaturia: Markers of Paracetamol-Induced Nephrotoxicity

1994 ◽  
Vol 31 (4) ◽  
pp. 331-334 ◽  
Author(s):  
C M Florkowski ◽  
A F Jones ◽  
J M Guy ◽  
D J Husband ◽  
J Stevens
Keyword(s):  
Renal Damage ◽  
Paracetamol Overdose ◽  
Retinol Binding Protein ◽  
Mechanism Of Toxicity ◽  
Renal Tubular Reabsorption ◽  
Biochemical Measurements ◽  
Tubular Toxicity ◽  
Urinary Parameters ◽  
Renal Tubular ◽  
Sensitive Marker

The occurrence of hypophosphataemia in paracetamol overdose suggests that nephrotoxicity is common, impaired renal tubular reabsorption of phosphate indicating renal damage. To investigate the potential nephrotoxicity of paracetamol, we studied 148 consecutive patients with paracetamol overdose. Serial clinical and biochemical measurements were made, and a fasting overnight urine collection was obtained for creatinine (Cr), phosphate and retinol-binding protein (RBP) determination. Renal threshold phosphate concentration (TmPO4/GFR) was determined from urinary parameters by an established nomogram. The degree of hypophosphataemia correlated with the severity of overdose, and with TmPO4/GFR. The median RBP/Cr ratio was higher in those patients exhibiting biochemical hepatotoxicity compared with those without hepatotoxicity, in whom median RBP/Cr was not significantly higher than controls. Within the group of patients showing biochemical hepatotoxicity, there was a correlation between log RBP/Cr and TmPO4/GFR. RBP/Cr ratio is a less sensitive marker of renal tubular toxicity than phosphaturia in these patients, and may indicate a different mechanism of toxicity.

scholarly journals Effect of zinc supplementation on chronic hepatorenal toxicity following oral exposure to glyphosate-based herbicide (Bushfire®) in rats

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052092534
Author(s):  
Emmanuel Vandi Tizhe ◽  
Najume Dogon-Giginya Ibrahim ◽  
Mohammed Yakasai Fatihu ◽  
Suleiman Folorunsho Ambali ◽  
Ikechukwu Onyebuchi Igbokwe ◽  
...  
Keyword(s):  
Chronic Exposure ◽  
Histopathological Examination ◽  
Serum Levels ◽  
Male Rats ◽  
Oral Exposure ◽  
Serum Samples ◽  
Tubular Necrosis ◽  
Serum Aspartate Aminotransferase ◽  
Liver And Kidney ◽  
Renal Tubular

Objectives To assess the effects of zinc pretreatment on hepatorenal toxicity following chronic exposure to glyphosate-based herbicides in male rats. Methods Following zinc pretreatment (50 mg/kg and 100 mg/kg), 14.4 to 750 mg/kg of oral glyphosate (Bushfire® herbicide) was administered daily for 36 weeks. Thereafter, serum samples were obtained following jugular venipuncture. Liver and kidney samples were processed for histopathological examination. Results Serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activity as well as levels of bicarbonate, calcium, creatinine were significantly increased following chronic exposure to Bushfire®. Serum levels of sodium, potassium, chloride, total protein, albumin, globulin and urea were unchanged. Moderate to severe coagulative necrosis of hepatocytes as well as glomerular and renal tubular necrosis were observed in herbicide-treated rats. Zinc pretreatment reduced the elevation of serum enzymes associated with hepatobiliary lesions, abrogated hypercalcemia and metabolic alkalosis, and mitigated serum accumulation of creatinine following Bushfire® exposure, but was ineffective in completely preventing histological lesions. Conclusion Chronic Bushfire® exposure in rats caused hepatorenal toxicity. The effects of exposure on serum parameters were ameliorated by zinc pretreatment, but the histopathological changes associated with toxicity persisted in milder forms in zinc-pretreated animals.

scholarly journals Tenofovir and Severe Symptomatic Hypophosphatemia

2019 ◽  
Vol 7 ◽  
pp. 232470961984879 ◽  
Author(s):  
Asim Kichloo ◽  
Savneek Singh Chugh ◽  
Sanjeev Gupta ◽  
Jay Panday ◽  
Ghazaleh Goldar
Keyword(s):  
Renal Damage ◽  
Organic Anion ◽  
Significant Risk ◽  
Anion Transporters ◽  
Immunodeficiency Virus ◽  
Tubular Lumen ◽  
Associated Proteins ◽  
Proximal Tubular ◽  
Renal Tubular ◽  
Initial Results

Tenofovir is a broadly used drug used for the treatment of human immunodeficiency virus (HIV). Although the initial results of the clinical trials supported the renal safety of Tenofovir, clinical use of it has caused a low, albeit a significant, risk of renal damage either in the form of AKI or CKD. The pathophysiology has been linked to the effect of this medication on the proximal tubular cell. Although the exact mechanism is unknown, studies have suggested that Tenofovir accumulates in proximal tubular cells which are rich in mitochondria. It is both filtered in the glomerulus and actively secreted in the tubules for elimination and is excreted unchanged in the urine. Studies have shown an active transportation of 20-30% of this drug into the renal proximal tubule (PCT) cells via the organic anion transporters in the baso-lateral membrane (primarily hOAT1, and OAT3 to a lesser extent) and ultimate excretion of the drug into the tubular lumen via the transporters in the proximal tubular apical membrane MRP4 and MRP2 (multidrug resistance-associated proteins 2 & 4). Subsequently, the mitochondrial injury caused by Tenofovir can lead to the development of Fanconi’s syndrome which causes renal tubular acidosis, phosphaturia, aminoaciduria, glucosuria with normoglycemia, and tubular proteinuria. Here we present a case where Tenofovir treatment resulted in severe hypophosphatemia requiring hospitalization for parentral phosphate repletion.

scholarly journals Pool water disinfection by ozone-bromine treatment: Assessing the disinfectant efficacy and the occurrence and in vitro toxicity of brominated disinfection by-products

2021 ◽  
Vol 204 ◽  
pp. 117648
Author(s):  
Fatima El-Athman ◽  
Lisa Zehlike ◽  
Alexander Kämpfe ◽  
Ralf Junek ◽  
Hans-Christoph Selinka ◽  
...  
Keyword(s):  
Water Disinfection ◽  
In Vitro Toxicity ◽  
Pool Water ◽  
By Products ◽  
Disinfectant Efficacy

Mammalian cell cytotoxicity and genotoxicity analysis of drinking water disinfection by-products

2002 ◽  
Vol 40 (2) ◽  
pp. 134-142 ◽  
Author(s):  
Michael J. Plewa ◽  
Yahya Kargalioglu ◽  
Danielle Vankerk ◽  
Roger A. Minear ◽  
Elizabeth D. Wagner
Keyword(s):  
Drinking Water ◽  
Mammalian Cell ◽  
Water Disinfection ◽  
Cell Cytotoxicity ◽  
Drinking Water Disinfection ◽  
By Products

Detection of genotoxic effects of drinking water disinfection by-products using Vicia faba bioassay

2016 ◽  
Vol 24 (2) ◽  
pp. 1509-1517 ◽  
Author(s):  
Yu Hu ◽  
Li Tan ◽  
Shao-Hui Zhang ◽  
Yu-Ting Zuo ◽  
Xue Han ◽  
...  
Keyword(s):  
Drinking Water ◽  
Vicia Faba ◽  
Water Disinfection ◽  
Genotoxic Effects ◽  
Drinking Water Disinfection ◽  
By Products

Abstract 893: Contrast Medium-Induced Renal Damage is Tightly Associated with Endothelial Injury in Patients

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kazuko Tajiri ◽  
Hidekazu Maruyama ◽  
Satoshi Sakai ◽  
Noritake Shimojo ◽  
Hideaki Aihara ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Contrast Medium ◽  
Renal Damage ◽  
Cell Activation ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Specific Marker ◽  
Before And After ◽  
Renal Tubular

Background: Contrast-induced nephropathy (CIN) remains a common complication of radiographic procedures. We hypothesized that endothelial dysfunction is the main cause of CIN. To clarify whether contrast medium-induced renal damage is associated with endothelial injury, we measured microparticles derived from endothelial cells as markers of endothelial injury. Circulating microparticles are shed from cell surface respond to cell activation and apoptotic stimuli, reflecting the condition of damaged cells. Methods: Renal function of 35 adult patients was analyzed before and after the use of contrast medium for coronary angiography. Parameters for renal function and urinary 15-isoprostane F2t, a specific marker of oxidative stress were measured before and after radiocontrast administration. Flow cytometry was used to count circulating CD34 + microparticles, which is regarded as one of markers for endothelial damage. Results: The decrease of estimated glomerular filtration rate positively correlated with the amount of contrast medium (r=0.427; P=0.013). Urinary N-acetyl-beta-D-glucosaminidase, a marker of renal tubular injury, was increased after angiography (from 7.6+/− 6.8 to 9.1 +/− 6.0 U/g-CRE, P=0.011). Furthermore, urinary 15-isoprostane F2t positively correlated with the volume of contrast medium (r=0.421; P=0.012). CD34+ microparticle was significantly increased after angiography (1.3-fold increased from basal level, P=0.0017). The increase of CD34+ microparticle was associated with the insult of contrast medium, but not of the amount. Conclusion: Radiocontrast impaired renal function in accordant with the increase of oxidative stress. The release of CD34+ microparticle was also increased by use of radiocontrast. These data suggest that CIN is tightly associated with endothelial injury mediated by radiocontrast-induced oxidative stress.

Three Patients with CPT1A Deficiency: Literature Review and Case Series

2020 ◽  
Author(s):  
Naser Ali Mirhosseini ◽  
Mahdieh Saatchi ◽  
Sana Taghiyar
Keyword(s):  
Genetic Disorder ◽  
Case Series ◽  
Autosomal Recessive Inheritance ◽  
Abnormal Liver Function Test ◽  
Medical Procedures ◽  
Main Method ◽  
Appropriate Treatment ◽  
Liver And Kidney ◽  
Renal Tubular

Background: Carnitine palmitoyltransferase 1A deficiency is a rare genetic disorder with autosomal recessive inheritance pattern of fatty acid metabolism secondary to CPT1A mutation. Several dozen infants and children have been described with a deficiency of the liver and kidney CPT1 isoenzyme (CPT1-A). Clinical manifestation includes fasting-induced hypoketotic hypoglycemia, occasionally with extremely abnormal liver function test (LFT) and rarely with renal tubular acidosis. Acyl carnitine analysis has been the main method for the diagnosis of CPT1A deficiency.  Prompt treatment of hypoglycemia includes intravenous fluid containing 10% dextrose. To prevent hypoglycemia, infants should eat frequently during the day and have cornstarch continuously at night. Fasting should not last more than 12 hours during illness, surgery, or medical procedures. Case Presentation: We reported three patients with CPT1A deficiency presented with hypoglycemia and Reye like syndrome in early childhood that with early diagnosis and treatment they are well in follow-up. Conclusion: Prognosis of this genetic disorder will be good with appropriate treatment.

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