Mar 31, 2015 molecular mechanism of drug induced nephrotoxicity 1. Symptoms may include abdominal pain, constipation, headaches, irritability, memory problems, inability to have children, and tingling in the hands and feet. Erythrophagocytosis of lead exposed erythrocytes by renal tubular cells. Pathophysiological mechanisms of calcineurin inhibitor. Jun 12, 2017 children with high lead exposure mean, 23. More side effects increased nephrotoxicity change in the drug metabolism 4. They had free access to standard rat pellet diet and water ad libitum. Health, general environmental issues erythrocytes physiological aspects kidney diseases risk factors lead health aspects lead metal red blood cells. Role of cadmium and lead in nephrotoxicity edelweiss publications. Effect of curcumin on inflammation and oxidative stress in. Abstract of research paper on chemical sciences, author of scientific article talib hussain, ramesh k gupta, k sweety, bavani eswaran, m vijayakumar, et al abstract objective to evaluate nephroprotective potential of solanum xanthocarpum s. Lvsa significantly attenuated leadinduced nephrotoxicity. Oxidative stress represents an imbalance between the production of free radicals and the.
Luteolin protects against lead acetateinduced nephrotoxicity. While protection is temporally associated with lead induced mitosis, occurring about 39 h after intracardiac lead. Goyer department of pathology, university of western ontario, london, ontario, n6a 5c1 canada summary exposure to lead results in accumulation in proximal renal tubular lining cells in the form of mor phologically discernible inclusion bodies which are lead protein complexes. Luteolin lut a flavonoid present in various plant products is well known for exhibiting numerous pharmacological properties. Data from clinical studies are not conclusive regarding the role of zinc transporters in cadmium induced nephrotoxicity. Drug induced nephrotoxicity is defined by the presence of any kidney injury caused directly or indirectly by medication. Nephrotoxicity can be defined as the adverse effect of substances on renal function perazella, 2009. The pathophysiological results, however, tend to diverge. Edelweiss applied science and technology, 2018 pdf.
Cadmium accumulates in renal tubular lining cells bound to metallothionein, a small protein contain ing 3070 cystine. Pathophysiology of nephrotoxic acute renal failure h umans are exposed intentionally and unintentionally to a variety of diverse chemicals that harm the kidney. Cadmium transporters in the kidney and cadmiuminduced. Renal tubular dysfunction and a cumulative impairment in kidney function, as manifested by a decline in the glomerular filtration rate gfr, can be dose limiting. The high level of lead exposure required to cause lead nephropathy is now increasingly rare, particularly in developed countries. Nephrotoxicity, biochemical alterations, lead, allium sativum, vitamin c, rats. Evaluation of urinary excretion of exosomal oat5 after nacetylcysteine prevention of cisplatin induced nephrotoxicity. Prediction of druginduced nephrotoxicity and injury. On the other hand, cnis are known to inhibit no synthesis and nomediated vasodilation and to increase free radical formation. Historical perspective of nephrotoxicity toxicological. Lead poisoning is a type of metal poisoning caused by lead in the body. Donaldsoneffect of lead toxicity on the organ concentration of glutathione and glutathionerelated free amino acids in the chick. Read lead reduces the nephrotoxicity of mercuric chloride, ecotoxicology and environmental safety on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Nov 15, 2007 recent evidence suggests that inflammation and oxidative stress may contribute to the pathogenesis of cisplatin induced acute renal failure.
Jan 15, 2016 lead is a biohazardous metal that is commonly involved in human illness including renal injury. At the point when kidney harm happens, patient cannot free his assortment of. Dec 27, 2019 aminoglycosides preferentially affect the proximal tubular cells. Leadinduced chronic renal failuredefinitionlead pb nephrotoxicity relates to experimental, epidemiologic, and clinical evidence of renal damage and hypertension associated to environmental or occupational pb exposure. The current work aimed at exploring the possible protective effect of. C 7, 10, 32, 48 druginduced renal impairment is generally reversible, provided the nephrotoxicity is recognized early and the offending medication is discontinued.
Nephrotoxicity is a complication due to the effect of some toxic chemicals on kidneys. Dosedependent effect of coriander coriandrum sativum l. Investigating nephrotoxicity with an integrated liver. Jul 01, 2010 data revealing the daytoday variations in scr level in a large group of patients who presumably had the same prevalence of risks to kidney function, including diabetes, as any large randomly chosen population of hospitalized patients 4 show that the range of such variations is just as large as those variations attributed to cm administration in nearly all published series and is even more. Nephrotoxicity definition of nephrotoxicity by the free.
Lead has many good uses, but too much can be harmful to humans and animals. Despite the recognition of lead nephropathy as a consequence of environmental and occupational lead exposure, lead nephropathy still appears to be underrecognized by physicians as a cause and promoter of chronic kidney disease ckd, especially in people with more apparent causative factors such as diabetes and hypertension. The aim of this work was to study the effect of natural honey on cadmiuminduced liver and kidney damage. With acute lead nephrotoxicity, these lead protein complexes are observed as typical intracellular inclusions. Ac may be beneficial in chronic lead induced liver and kidney damage. Aminoglycoside type antibiotic gentamicin is one of the leading cause of drug induced nephrotoxicity. Effect of curcumin and curcumin nanoparticles against lead. Recent evidence suggests that inflammation and oxidative stress may contribute to the pathogenesis of cisplatin induced acute renal failure. Finally, determination of a patients or donors genotype of drugmetabolizing genes or of mol ecules involved in csa nephrotoxicity. Protective effects of piperine on lead acetate inducednephrotoxicity. Nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy.
Pdf lead induced nephrotoxicity with special reference to. Silymarin and dimercaptosuccinic acid ameliorate lead induced nephrotoxicity and genotoxicity in rats show all authors. The association between lead exposure and nephrotoxicity has been wellestablished, even in a population with blls as low as 5. Pdf protective effects of piperine on lead acetate induced. We evaluated the protective efficacy of lut against pb induced renal injury in male wistar.
Potential complications of lead nephropathy include gout and hypertension. Nacetylcysteine nac is a potent oxygen free radicals scavenger and a metal chelator. Pathophysiologic mechanisms of selected types of nephrotoxicity. Risk factors for chemotherapy induced nephrotoxicity. Mda may be used as an indicator of cell membrane damage after exposure to ros and free radicals. Nephrotoxins are substances displaying nephrotoxicity nephrotoxicity should not be confused with the fact that some medications are predominantly excreted by. Bennett, md division of nephrology, hypertension, and clinical pharmacology oregon health sciences university portland, oregon, usa the kidney is the major site of damage from many drugs and chemicals that are used in clinical medicine and are present in our environment. Despite dramatic improvements in patient survival and drug tolerability, nephrotoxicity remains an important complication of chemotherapy. Reports of nephrotoxicity research continue to increase each decade with only 80 articles before 1970 to over 5300 papers between 2010 and 2018. Lead pb toxicity remains a significant public health problem because of its global pervasiveness and its adverse effects on the renal system. The 6rs of drug induced nephrotoxicity linda awdishu1,2 and ravindra l. Research, report by environmental health perspectives. If unchecked, the kidney failure may lead to the death.
One, two, or all three of the factor categories can act to promote various forms of renal injury. Mechanisms of antimicrobialinduced nephrotoxicity in. Chronic nephropathy is one of the oldest recognized health effects of lead. The causative drug must be identified and its use must be. Different classes of drugs, by virtue of immunological mechanisms or direct toxicity initiate certain stereotyped renal responses. The aim of this study was to evaluate the antioxidant activity of chitosan pinus merkusii extract nanoparticle on lead acetate induced toxicity in rat pancreas. It induces nephrotoxicity with significant alterations in renal structure and function. As the list of drugs, natural products, industrial chemicals and environmental pollutants that cause nephrotoxicity. Mehta2 abstract drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization.
It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. Nephrotoxicity and agents responsible nephrotoxic injury is damage to one or both kidenys that result from exposure to a toxic substance. They are broadly categorized as patientspecific, kidneyrelated, and drugrelated factors. Mechanisms of lead and cadmium nephrotoxicity sciencedirect.
Drug induced nephrotoxicity is responsible for 20% to 60% of cases of acute kidney injury in hospitalized patients and is associated with increased morbidity and mortality in both children and adults. These substances can include molds and fungi, cancer therapeutics such as cisplatin, antibiotics such as aminoglycosides, metals such as mercury, arsenic and lead, and drugs of abuse such as cocaine. There has been a growing awareness that nephrotoxicity represents a key factor in human nephropathies, where, irrespective of the causative agent, only a few clinical endeffects are diagnosed. Onconephrology is a new area that is rapidly expanding and requires a close working relationship between oncologists and nephrologists. The increase in mda levels in kidney suggests that antioxidant failure to inhibit ros and formation of free radicals can enhance lipid peroxidation causing. It is important for the treatment of acute and chronic free radical mediated diseases and toxicity. The aim of the present study is to clarify the possible corrective role of curcumin on the nephrotoxicity induced by lead acetate. Figure6 various sites of the drug induced nephrotoxicity the nephrotoxic substances causes nephrotoxicity.
Epidemiological and toxicological studies have reported lead induced toxicity in the nervous, cardiovascular, and renal systems agency for toxic substances and disease registry atsdr 2007. Cnis lead to activation of the major vasoconstriction systems, such as the reninangiotensin and endothelin systems, and increase sympathetic nerve activity. Protective effect of nacetylcysteine on experimental chronic. Protective effects of spirulina against hematobiochemical. Preventing nephrotoxicity induced by lead in albino rats. Lead acetate, berberis vulgaris, mice, nephrotoxicity, antioxidant enzymes, lipids peroxidation. Relationship between various biological exposure indices and early markers of nephrotoxicity, american journal of industrial medicine on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Cisplatin is a potent and valuable chemotherapy agent used to treat a broad spectrum of malignancies.
Cadmium and lead are divalent cations with a propensity to settle in the proximal tubule of the nephron, leading to nephrotoxicity. The present study was performed to explore the effect of curcumin against cisplatin induced experimental nephrotoxicity. The therapeutic properties of natural honey once considered a form of folk or preventive medicine. Erythrophagocytosis of leadexposed erythrocytes by renal tubular cells. Lead induced hepatorenal damage in male albino rats. Chitosan pinus merkusii nanoparticles were identified by particle size analysis psa and scanning electron microscope sem. The current study was carried out to evaluate the antioxidant and anticaspase 3 activity of chitosan pinus merkusii nanoparticle in against lead acetate induced nephrotoxicity in rats.
Seventytwo adult male rats were equally divided to 6 groups. Oxidative stress plays a key role in lead pbinduced nephrotoxicity. Nephrotoxicity and chinese herbal medicine american society. Clinical pharmacology for the nephrologist khaled eldahshan, md lecturer of nephrology, mansoura. Lead acetate nephrotoxicity, glomerular blood flow, oxidative stress, low viscosity sodium alginate, proximal convoluted tubules. Chronic lead exposure has been implicated in renal failure in. The potency of chitosanpinus merkusii extract nanoparticle. Drug induced kidney diseases np singh, a ganguli, a prakash abstract drug induced kidney disease constitutes an important cause of acute renal failure and chronic kidney disease in present day clinical practice. Moreover, great at tention should be paid to drug interactions. Microanatomy and histomorphometry analysis of the effects.
Current study planned to screen the effect of coriander and fennel aqueous seeds extracts on lead induced nephrotoxicity. Toxicology letters, 46 1989 153162 153 txl 02127 mechanisms of lead and cadmium nephrotoxicity r. Original article nephroprotective effect of low viscosity. Some of these herbal medicines are also known to cause nephrotoxicity, which is often overlooked by physicians and patients due to the belief that herbal medications are innocuous. Antimicrobials are one of the most common classes of medications prescribed globally and also among the most common causes of nephrotoxicity. Autophagy blockade and lysosomal membrane permeabilization. Efficacy of curcumin on lead induced nephrotoxicity in.
Cisplatin induced nephrotoxicity is characterized by renal proximal tubular cell dysfunction. Gammaglutamyl cysteine attenuates tissue damage and enhances. The presentation varies from an acute or chronic reduced glomerular filtration rate gfr to nephrotic syndrome and hydroelectrolytic disorders hed related, respectively, to glomerular and tubular damage. Investigating nephrotoxicity with an integrated liverkidney chip. Luteolin ameliorates colistininduced nephrotoxicity in the. In this condition the kidney function deteriorates and may lead to chronic kidney failure. Lead exposure and kidney function lead is a natural element found in small amounts in the earth. Drug induced kidney disease occurs primarily in patients with underlying risk factors. This study aimed to investigate the potential effects of berberis vulgaris l. Effect of curcumin and curcumin nanoparticles against lead induced nephrotoxicity. The clinical diagnosis of lead nephropathy is complex, because the symptoms are varied and nonspecific especially with subclinical nephrotoxicity. Female rats aged 12 weeks were treated for 4 weeks with pb 0. Lead and cadmium are the two most commonly known nephrotoxic metals.
Victoriya sidorenko and colleagues elucidate the specific steps in the liver and kidney that lead to aristolochic acid. Based on the study, it can be stated that lead induced nephrotoxicity particularly. This may reflect a true phenomenon because lead exposure has been reported to accelerate bony maturation by inhibiting the effects of parathyroid hormonerelated peptide. This case shows methotrexate crystals deposited within the kidney tubules of a pati. Nephroprotective activity of solanum xanthocarpum fruit. It seems that an enhanced activity of mts contributes to cadmium induced nephrotoxicity. Lead pb is one of the most common heavy metal pollutants affecting living organisms. Ijms free fulltext cadmium transporters in the kidney. Chinese herbal medicine is composed mainly of natural compounds with complex active ingredients that can lead to varying degrees of side effects. Although it is a nonredox reactive metal, leadinduced renal injury is largely based on oxidative stress.
Drug induced nephrotoxicity is caused by nephrotoxic drugs or toxins which damage kidneys and can lead to nephritis or renal toxicity. The current study was aimed at exploring the protective efficacy of spirulina against the hematobiochemical alterations and nephrotoxicity induced by lead pb. It causes almost 10% of intellectual disability of otherwise unknown cause and can result in behavioral problems. Pdf lead pollution is one of the most important problems of environmental and occupational origin and is widely regarded as risk to health. Erythrophagocytosis of leadexposed erythrocytes by renal. Lead is absorbed by the proximal tubular cells of the renal tubules, where it binds to specific lead binding proteins.
Indigofera oblongifolia mitigates lead acetate induced kidney damage and apoptosis in a rat model mohamed a dkhil,1,2 mohamed s alkhalifa,1 saleh alquraishy,1 rafat zrieq,3 ahmed esmat abdel moneim2 1department of zoology, college of science, king saud university, riyadh, saudi arabia. Introduction lead pb is a heavy metal distributed into the environment from natural and anthropogenic sources and. The nephrotoxic effect of a single intraperitoneal dose of mercuric chloride hgcl 2. Medical and environmental applications of activated charcoal. Some of the reason for this is that chronic renal disease from lead exposure does not become evident until late in life and usually after many years of excessive exposure. Our current knowledge of drug induced kidney disease is. Lead induced chronic renal failuredefinitionlead pb nephrotoxicity relates to experimental, epidemiologic, and clinical evidence of renal damage and. A number of factors have been identified as adding risk to the development of tdf induced nephrotoxicity including advanced age, low body mass index bmi, diabetes mellitus dm, hypertension htn, couse of other nephrotoxic drugs such as protease inhibitors pi and didanosine, treatment experience, and genetic polymorphism in transporters involved in regulating tdf intracellular. In recent years gentamicin nephrotoxicity is significantly reduced by shifting to once daily dosage as well as by eliminating known risk factors. Adverse renal effects occur because of innate drug toxicity and a number of patient and drugrelated factors. This study evaluated the effects of lead exposure on the histoarchitecture of kidney, assessed the effects of lead on the levels of creatinine, urea and albumin in the plasma and determined the effects of m. Searching pubmed using nephrotoxicity as the search term results in 16,008 related papers, with the earliest paper cited describing the nephrotoxicity induced by cystine.
Acute methotrexateinduced crystal nephropathy nejm. Oxidative stress plays a key role in lead induced nephrotoxicity. Methotrexate induced nephrotoxicity is not uncommon, although intrarenal methotrexate crystals have been elusive. Thus, this study has been designed to investigate the effect of low viscosity sodium alginate lvsa in lead induced nephrotoxicity. Nephrotoxicity results from lead exposure because the kidney is the main route by which lead is eliminated. Protective effects of piperine on lead acetate inducednephrotoxicity in rats.
This was with a view to providing information on the ameliorative effects. In the present study we examined the role of erythrocytes in lead induced nephrotoxicity in vitro in a coculture system as well as in vivo in rats. Mar 24, 2017 due to high relative blood flow the kidney is prone to drug induced damage. Acute nephrotoxicity consists of proximal tubular dysfunction and can be reversed by treatment with chelating agents. On the basis of available evidence, we hypothesized that lead induced ps externalization in erythrocytes promotes erythrophagocytosis by renal tubular cells, contributing to lead associated kidney. Metallothionein protects against nephrotoxicity by binding cadmium in a nontoxic form. Silymarin and dimercaptosuccinic acid ameliorate lead. Renal vulnerability to drug toxicity american society of. Mice were exposed chronically to lead acetate, at a dose of 5 mgkg, alone or in conjunction with b. Indigofera oblongifolia mitigates leadacetateinduced kidney. Nephrotoxins are chemicals displaying nephrotoxicity. Sabah ansar 1, sarah farhat2, aljohara am albati 3, manal abudawood 1, sherifa hamed4 1clinical laboratory sciences, applied medical sciences, king saud university, saudi arabia 2lawrence high, lawrence, kansas, usa 3clinical health sciences, applied medical sciences, king saud university, saudi arabia. Jul 27, 2015 drug induced nephrotoxicity can lead to acute kidney injury aki or chronic kidney disease in patients and is a major problem for clinicians 2,3. There are various forms, and some drugs may affect kidney function in more than one way.
Lead is one of the heavy metals with oxidative stress that causes toxicity in human and animals. Nephroprotective effect of costus afer on lead induced kidney. Lead reduces the nephrotoxicity of mercuric chloride. These substances can include molds and fungi, cancer therapeutics such as cisplatin, antibiotics such as aminoglycosides, metals such as mercury, arsenic and lead, and drugs of. Lead exposure and kidney function national kidney foundation. Thus nephropathies are generally classified as acute or chronic renal failure, malignancies or. Epidemiological and toxicological studies have reported leadinduced toxicity in the nervous, cardiovascular, and renal systems agency for toxic substances and disease registry atsdr 2007.
In another study, the inhibition of enzymes apn, rdp, and cs lyase did not protect rats given 10 mgkg of cisplatin andor rats treated with 6 mgkg from cisplatin induced nephrotoxicity. Organic anion transporter 5 oat5 urinary excretion is a specific biomarker of kidney injury. Chronic lead nephrotoxicity consists of interstitial fibrosis and progressive nephron loss, azotaemia and renal failure. Oxidative stress can play a key role in cadmiuminduced dysfunction. The present study was performed to explore the effect of curcumin against cisplatin. Understanding and managing methotrexate nephrotoxicity.
These agents are freely filtered by the glomeruli and quickly taken up by the proximal tubular epithelial cells, where they are incorporated into lysosomes after first interacting with phospholipids on the brush border membranes. Lead induced oxidative stress and its recovery following coadministration of melatonin or nacetylcysteine during chelation with. A number of factors enhance the vulnerability of the kidney to the nephrotoxic effects of drugs and toxins. Curcumin is claimed to be a potent antiinflammatory and antioxidant agent. To provide cutting edge care for these patients, nephrologists and oncologists must be familiar with the nephrotoxicity of these drugs.