Immunomodulatory response and serum level of neutrophil gelatinase associated lipocalin (NGAL) as a marker of acute kidney injury in wistar rats exposed to pyrethroids
TL;DR: It is observed that pyrethroids can cause oxidative stress, deplete antioxidant levels, nephrotoxicity, and may modulate both humoral and cellular immune functions, and established NGAL as a sensitive diagnostic tool and early biomarker for acute kidney injury (AKI).
Abstract: BACKGROUND: Insecticide usage has increased in the tropics and subtropics due to the high prevalence of vector-borne infections, even though insecticide use effectively reduces insect-borne diseases. Insecticide exposure can cause oxidative stress and have severe consequences for human health. The study was then designed to evaluate oxidative stress and its effects on immunomodulatory and renal integrity among Wistar rats exposed to pyrethroids. METHODS: Eighty-four Wistar rats were randomly selected and divided into two groups. Fifty-one rats were exposed to 1.2 %w/v pyrethroids, while the remaining thirty-three rats were grouped as non-exposed. The groups were divided into three different groups, each with 7, 21, and 41 days. After days of exposure, the animals in each group were anesthetized, and blood samples were collected from the inferior vena cava. Using standard spectrophotometric techniques, the levels of total antioxidant status (TAS), malondialdehyde (MDA), glutathione (GSH), hydrogen peroxide (H2O2), urea, creatinine and uric acid were determined. Blood activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) were determined. ELISA was used to determine levels of IgG, IgA, IgE, TNF-α, and NGAL. Data obtained were statistically compared. RESULTS: The serum mean levels of SOD, GPx, CAT, GSH, and TAS were significantly reduced (p < 0.05) while mean levels of MDA, H2O2, IgG, IgE, IgA, TNFα, neutrophil gelatinase-associated lipocalin (NGAL), urea, uric acid, and creatinine were significantly elevated (p < 0.05) from 7 to 41 days exposure in exposed groups. NGAL had a higher area under the ROC curve than urea and creatinine. CONCLUSIONS: This study observed that pyrethroids can cause oxidative stress, deplete antioxidant levels, nephrotoxicity, and may modulate both humoral and cellular immune functions. It also established NGAL as a sensitive diagnostic tool and early biomarker for acute kidney injury (AKI).
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TL;DR: Clinical implications are reviewed, and recommendations are made regarding the integration of this environmental health concern into nursing education, practice, research, and policy/advocacy work.
Abstract: Pesticides are a category of chemicals formulated to kill or repel a pest or halt its reproduction. In this article we review the toxicological and epidemiological literature; describe common potential pesticide exposures; and focus on the associated health risks to fetal development. Clinical implications are reviewed, and recommendations are made regarding the integration of this environmental health concern into nursing education, practice, research, and policy/advocacy work. Recommendations for pesticide elimination and reduction in health care settings are included.
440 citations
TL;DR: The nature of such damage, the cellular conditions in which it occurs, and oxidative-stress data that may be applied to the development of risk-assessment methods and models that are designed to reduce some of these uncertainties are reviewed.
Abstract: Pesticide-induced oxidative stress as a possible mechanism of toxicity has been a focus of toxicological research for the last decade. Yet for certain pesticides, mechanisms leading to oxidative stress are only partly understood. Pesticide-induced oxidative stress is the final manifestation of a multi-step pathway, resulting in an imbalance between pro-oxidant and antioxidant defense mechanisms. Concomitantly, pesticide intoxication induces a derangement of certain antioxidant mechanisms in different tissues, including alterations in antioxidant enzymes and the glutathione redox system. In this article, we discuss the impact of certain factors that are important in the potentiation of pesticide-induced oxidative stress, immunotoxicity, and apoptosis. Understanding risk factors largely depends upon the cellular and molecular events underlying pesticide-induced stress in experimental animals. These factors must be considered in the safety/toxicity evaluation of any pesticide. The identification and characterization of plant products/drugs might be helpful for understanding the mechanisms of compensation and repair that are due to oxidative stress-induced injury. This paper reviews the nature of such damage, the cellular conditions in which it occurs, and oxidative-stress data that may be applied to the development of risk-assessment methods and models that are designed to reduce some of these uncertainties.
377 citations
TL;DR: The discovery, translation and validation of neutrophil gelatinase‐associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed and is emerging as an excellent stand‐alone troponin‐like structural biomarker in the plasma and urine for the early diagnosis of AKI.
Abstract: Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which currently depends on functional markers such as serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers of structural kidney injury (akin to troponin in acute myocardial injury) has hampered our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The discovery, translation and validation of neutrophil gelatinase-associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed. NGAL is emerging as an excellent stand-alone troponin-like structural biomarker in the plasma and urine for the early diagnosis of AKI, and for the prediction of clinical outcomes such as dialysis requirement and mortality in several common clinical scenarios. The approach of using NGAL as a trigger to initiate and monitor therapies for AKI, and as a safety biomarker when using potentially nephrotoxic agents, is also promising. In addition, it is hoped that the use of sensitive and specific biomarkers such as NGAL as endpoints in clinical trials will result in a reduction in required sample sizes, and hence the cost incurred. Furthermore, predictive biomarkers like NGAL may play a critical role in expediting the drug development process. However, given the complexity of AKI, additional biomarkers (perhaps a panel of plasma and urinary biomarkers) may eventually need to be developed and validated for optimal progress to occur.
339 citations
TL;DR: The results of the present study suggest the usefulness of RBC AChE measurement as a good biomarker in the estimation of malathion-induced oxidative stress affecting blood and liver.
Abstract: Organophosphorus compounds may induce oxidative stress leading to generation of free radicals and alterations in antioxidant and scavengers of oxygen free radicals (OFRs). The effect of subchronic exposure to malathion in the production of oxidative stress was evaluated in male Wistar rats. Administration of malathion (100, 316, 1000, 1500 ppm) for 4 weeks increased catalase (CAT), superoxide dismutase (SOD) activities as well as malondialdehyde (MDA) concentration in red blood cells (RBC) and liver. However, acetylcholinesterase (AChE) and cholinesterase (ChE) activities were decreased in these samples. The increase in RBC and liver lipid peroxidation correlated well with the inhibition in RBC AChE and liver ChE activities. Elevation of MDA concentrations and increased activities of CAT and SOD showed significant correlations in both RBC and liver samples when different doses of malathion were used. The results of the present study suggest the usefulness of RBC AChE measurement as a good biomarker in the estimation of malathion-induced oxidative stress affecting blood and liver.
338 citations
TL;DR: The world's disease profile is changing, and chronic diseases now account for the majority of global morbidity and mortality, rather than infectious diseases, and diabetes is now the major cause of end-stage renal failure worldwide.
261 citations