Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

Current Knowledge of Selected Cardiovascular Biomarkers in Pediatrics: Kidney Injury Molecule-1, Salusin-α and -β, Uromodulin, and Adropin

Cardiovascular diseases are the leading cause of morbidity and mortality in the modern world. Their common denominator is atherosclerosis, a process beginning in childhood. In pediatrics, the aim of preventive measures is to recognize children and adolescents at risk for accelerated atherosclerosis and possible premature cardiovascular events in adulthood. Several diagnostic procedures and biomarkers are available for cardiovascular risk assessment in adults. However, reliable markers in pediatrics are still insufficiently studied. In this contribution, we discuss five potential biomarkers of particular interest: kidney injury molecule-1, salusin-α and -β, uromodulin, and adropin. Studies regarding the pediatric population are scarce, but they support the evidence from studies in the adult population. These markers might entail both a prognostic and a therapeutic interest.

La proteína KIM-1, un biomarcador asociado a la enfermedad renal

La enfermedad renal o de riñón es una anormalidad funcional de los riñones que tiene implicaciones en la salud. El daño agudo de riñón y la enfermedad renal crónica presentan una elevada incidencia en México y representan un problema de salud pública con repercusiones económicas importantes. El diagnóstico oportuno de la enfermedad renal tendría un efecto positivo en la eficacia del tratamiento y en el pronóstico de la enfermedad. KIM-1(Kidney Injury Molecule-1) es una glicoproteína que actúa como receptor para fosfatidilserina y TIM-4 (T-Cell Immunoglobulin and Mucin Domain-4); aunque se expresa en diferentes células y tejidos, su expresión se produce principalmente en células del epitelio tubular proximal de las nefronas. En personas sanas KIM-1 no se expresa, pero durante el daño en las células epiteliales tubulares, se sobreexpresa y su fracción soluble es secretada en orina y/o filtrada a la sangre, lo que aumenta su concentración y permite su detección en estos fluidos; por esta razón, se ha propuesto como un biomarcador de daño renal. En fases tempranas, KIM-1 tiene una función protectora ante el insulto renal, pero su expresión sostenida en células del epitelio tubular se ha asociado con la enfermedad renal crónica y la fibrosis renal. En esta revisión, describimos la estructura de KIM-1, su expresión y su función tanto en el sistema inmunológico como en la enfermedad renal.

Markers of kidney tubular and interstitial injury and function among sugarcane workers with cross-harvest serum creatinine elevation

ObjectivesSerum creatinine (SCr) is a routine marker of kidney injury but also increases with dehydration and muscular work. This study was to elucidate whether increase in SCr is associated with more specific markers of kidney tubular and interstitial injury and function, during prolonged heat stress among workers at high risk of chronic kidney disease of non-traditional origin (CKDnt).MethodsUrine monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), calbindin, glutathione S-transferase-π (GST-π), clusterin, interleukin 18 and albumin, fractional excretion of potassium (FEK), blood haemoglobin, serum potassium, ferritin and erythropoietin were measured before and after harvest in a sample of 30 workers with a ≥0.3 mg/dL SCr increase across harvest (cases), and 53 workers with stable SCr (controls).ResultsUrine MCP-1 (p for differential cross-harvest trend <0.001), KIM-1 (p=0.002), calbindin (p=0.02), GST-π (p=0.04), albumin (p=0.001) and FEK (p<0.001) increased in cases, whereas blood haemoglobin (p<0.001) and serum erythropoietin (p<0.001) decreased.ConclusionSeveral markers of tubular and interstitial injury and function changed as SCr increased across a harvest season, supporting the use of SCr as an indicator of kidney injury in physically active workers regularly exposed to heat stress. Repeated injury similar to that described here, and continued work under strenuous and hot conditions with similarly elevated injury markers is likely to worsen and possibly initiate CKDnt.

KIM-1 and GADDI-153 gene expression in paracetamol-induced acute kidney injury: effects of N-acetylcysteine, N-acetylmethionine, and N-acetylglucosamine

Objectives Acute kidney injury (AKI) is a critical clinical event characterized by a reduction in the excretory function of the kidneys. N-acetylcysteine (NAC), N-acetylmethionine (NAM) and N-acetylglucosamine (NAG) are antioxidants with scanty known genetic mechanisms. We aimed to assess both kidney injury molecule-1 (KIM-1) and growth-arrested DNA damage-inducible gene-153 (GADD-153) genes expression in paracetamol (PA) induced AKI. Also, to recognize whether NAC, NAM and/or NAG have roles in altering the expression of these genes for ameliorating the AKI induced by PA. Methods The present preliminary study achieved the AKI model by oral administration of PA therapeutic dose for 15 days in experimental male rats. Serum urea, creatinine, and renal oxidative stress parameters were analyzed. Genetic expression of KIM-1 and GADD-153 were determined using real time-PCR. Results Significant elevations of serum urea, creatinine and nitric oxide in renal tissue after PA administration; however, total thiol content was reduced. In addition, both KIM-1 and GADD-153 were upregulated. These biochemical alterations were improved after using NAC and partially after NAM; however, NAG had little effect. Conclusions Up-regulation of both KIM-1 and GADD-153 occur in AKI induced by PA, which was significantly reversed by NAC.

Blood and Urine Biomarkers Predicting Worsening Kidney Function in Patients with Type 2 Diabetes Post-Acute Coronary Syndrome: An Analysis from the EXAMINE Trial

<b><i>Introduction:</i></b> Worsening kidney function (WKF) is frequent among patients with type 2 diabetes (T2D) and a recent acute coronary syndrome (ACS) and is associated with a poor prognosis. An accurate prediction of WKF is clinically important. <b><i>Aims:</i></b> Using data from the Cardiovascular Outcomes Study of Alogliptin in Patients with Type 2 Diabetes and Acute Coronary Syndrome trial including patients with T2D and a recent ACS, and a large biomarker panel incorporating proteins measured both in blood and urine, we aim to determine those with best performance for WKF prediction. <b><i>Methods:</i></b> WKF was defined as a ≥40% estimated glomerular filtration rate (eGFR) drop from baseline, eGFR &#x3c;15 mL/min, or dialysis. Mixed-effects and time-updated Cox models were used. <b><i>Results:</i></b> 5,131 patients were included from whom 222 (4.3%) developed at least one WKF episode over a median follow-up of 18 months. Patients who developed WKF were more frequently women, had longer diabetes duration, a more frequent heart failure history, higher anemia prevalence, and impaired kidney function. In multivariable models including all variables (clinical and biomarkers) independently associated with WKF with a <i>p</i> value ≤0.0001, blood kidney injury molecule 1 (KIM-1) was (by far) the variable with strongest WKF association, followed by anemia. KIM-1 alone provided good discrimination for WKF prediction (area under the curve = 0.73). Patients in the high KIM-1-derived risk tertile had a 6.7-fold higher risk of any WKF than patients classified as low risk. In time-updated Cox models, the occurrence of WKF was independently associated with a higher risk of death: adjusted hazard ratio = 4.93 (3.06–7.96), <i>p</i> value &#x3c;0.0001. <b><i>Conclusion:</i></b> Blood KIM-1 was the biomarker with the strongest association with WKF. The occurrence of WKF was independently associated with a higher risk of subsequent cardiovascular events and mortality.

Urinary Biomarkers of Mycotoxin Induced Nephrotoxicity—Current Status and Expected Future Trends

The intensifying world-wide spread of mycotoxigenic fungal species has increased the possibility of mycotoxin contamination in animal feed and the human food chain. Growing evidence shows the deleterious toxicological effects of mycotoxins from infants to adults, while large population-based screening programs are often missing to identify affected individuals. The kidney functions as the major excretory system, which makes it particularly vulnerable to nephrotoxic injury. However, few studies have attempted to screen for kidney injury biomarkers in large, mycotoxin-exposed populations. As a result, there is an urgent need to screen them with sensitive biomarkers for potential nephrotoxicity. Although a plethora of biomarkers have been tested to estimate the harmful effects of a wide spectrum of toxicants, β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) are currently the dominant biomarkers employed routinely in environmental toxicology research. Nevertheless, kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are also emerging as useful and informative markers to reveal mycotoxin induced nephrotoxicity. In this opinion article we consider the nephrotoxic effects of mycotoxins, the biomarkers available to detect and quantify the kidney injuries caused by them, and to recommend biomarkers to screen mycotoxin-exposed populations for renal damage.