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Background:Star fruit (SF) is a popular fruit, commonly cultivated in many tropical countries, that contains large amount of oxalate. Acute oxalate nephropathy and direct renal tubular damage through release of free radicals are the main mechanisms involved in SF-induced acute kidney injury (AKI). The aim of this study was to evaluate the protective effect of N-acetylcysteine (NAC) on SF-induced nephrotoxicity due to its potent antioxidant effect. Materials and methods:Male Wistar rats received SF juice (4 mL/100 g body weight) by gavage after a 12 h fasting and water deprivation. Fasting and water deprivation continued for 6 h thereafter to warrant juice absorption. Thereafter, animals were allocated to three experimental groups: SF (n = 6): received tap water; SF + NAC (n = 6): received NAC (4.8 g/L) in drinking water for 48 h after gavage; and Sham (n = 6): no interventions. After 48 h, inulin clearance studies were performed to determine glomerular filtration rate. In a second series of experiment, rats were housed in metabolic cages for additional assessments. Results:SF rats showed markedly reduced inulin clearance associated with hyperoxaluria, renal tubular damage, increased oxidative stress and inflammation. NAC treatment ameliorated all these alterations. Under polarized light microscopy, SF rats exhibited intense calcium oxalate birefringence crystals deposition, dilation of renal tubules and tubular epithelial degeneration, which were attenuate by NAC therapy. Conclusions:Our data show that therapeutic NAC attenuates renal dysfunction in a model of acute oxalate nephropathy following SF ingestion by reducing oxidative stress, oxaluria, and inflammation. This might represent a novel indication of NAC for the treatment of SF-induced AKI. [ABSTRACT FROM PUBLISHER]

Purpose: To identify benefit ofN-acetylcysteine (NAC) on patients with pre-existing renal insufficiency or diabetes.Background: NAC administration is a common method for prevention of contrast-induced nephropathy (CIN). Nevertheless, its benefit on patients with pre-existing renal insufficiency or diabetes remains uncertain and controversial.Methods:Randomized controlled trials (RCTs) to evaluate the efficacy of NAC for the prevention of CIN in patients with pre-existing renal insufficiency or diabetes were searched from the databases of MEDLINE, EMBASE, and Cochrane library. Pooled odds ratio (OR) with 95% confidence interval (95% CI) were calculated using fixed-effects model by the Mantel–Haenszel test.Results: Twenty RCTs involving 3466 subjects (1756 assigned to NAC and 1710 assigned to the control) were included in the pre-existing renal dysfunction group. Pooled analysis suggested a significant reduction in CIN among this group (OR, 0.76; 95% CI, 0.61–0.93;p = 0.008). However, the nine trials comparing NAC versus control among patients with diabetes (NAC, 367 subjects; control, 358 subjects) showed no benefit of NAC for prevention of CIN (OR = 0.87; 95% CI, 0.58–1.30;p = 0.50). No significant heterogeneity was detected (p = 0.07;I2 = 34% for the group of pre-existing renal dysfunction;p = 0.40;I2 = 5% for the group of diabetes).Conclusion: Our results suggest that NAC decreases the incidence of contrast-induced nephropathy among patients with pre-existing renal insufficiency. The benefit was not existed in patients with diabetes. [ABSTRACT FROM PUBLISHER]

Background: We investigated the anti-inflammatory and protective effects of concomitant use of dexpanthenol (DXP) and N-acetylcysteine (NAC) induced ischemia/reperfusion (I/R) injury of kidney. Methods: Forty rats were randomly divided into 5 groups. In all groups except for Group 1(Sham), renal arteries bilaterally occluded with vascular clamp for IR injury. Group 1(Sham), received a single dose of 10 mL/kg isotonic saline daily by intraperitoneal (IP) injection for three days. Group 2(IR), received a single dose of 10 mL/kg isotonic saline daily by IP injection for three days. Group 3(IR + NAC), received 300 mg/kg NAC daily by IP injection for three days. Group 4(IR + DXP), received 500 mg/kg DXP daily by IP injection for three days. Group 5(IR + NAC + DXP), received 500 mg/kg DXP and 300 mg/kg NAC daily by IP injection for three days. Serum urea (BUN), creatinine (Cr) and neutrophil gelatinase-associated lipocalin (NGAL, lipocalin 2, siderocalin) levels were measured as kidney function tests. TNF-α levels were measured as inflammatory marker. Tissue sections were evaluated histopathologically under light microscopy. Results: IR + NAC + DXP group received both NAC and DXP before induction of renal I/R and as the biochemical and histopathological data revealed the results of the IR + NAC + DXP group and sham group were similar. Biochemically and histopathologically, combined use of NAC and DXP has better results when each of them used alone. Conclusion: We concluded that concomitant use of DXP and NAC plays a major role against I/R injury and may be useful in acute treatment of I/R induced renal failure. [ABSTRACT FROM AUTHOR]

Introduction: Acetaminophen (APAP) is an analgesic and antipyretic agent. In overdoses, it is associated with nephrotoxicity. We examined the potential protective effects of N-acetylcysteine (NAC) and NAC + ozone therapy (OT) combination against APAP-induced nephrotoxicity. Materials and methods: Thirty-two male Sprague-Dawley rats were divided into four groups: sham, control (APAP), NAC, and NAC + OT. In the APAP, NAC, and NAC + OT groups, kidney injury was induced by oral administration of 1 g/kg APAP. The NAC group received NAC (100 mg/kg/day). NAC + OT group received NAC (100 mg/kg/day) and ozone/oxygen mixture (0.7 mg/kg/day) intraperitoneally for 5 days immediately after APAP administration. All animals were killed at 5 days after APAP administration. Renal tissues and blood samples were obtained for biochemical and histopathological analyses. Neopterin, tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-10 levels were measured in sera. Malondialdehyde (MDA) levels and glutathione peroxidase (GPx) activities were determined in renal homogenates. Results: NAC and NAC + OT significantly decreased MDA and TNF-α levels and increased IL-10 levels and GPx activities. Serum neopterin and IL-6 levels were not different among all groups. APAP administration caused tubular necrosis in the kidney. The degrees of renal necrosis of the APAP group were higher than the other groups. Renal injury in rats treated with combination of NAC and OT were found to be significantly less than the other groups. Conclusions: Our results showed that NAC and OT prevented renal injury in rats and reduced inflammation. These findings suggest that combination of NAC and OT might improve renal damages because of both oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Background and Aims: Acute hepatic injury causes systematic inflammatory responses which may finally lead to functional disturbances in remote organs. In this study, the effects of an inhibitor of inflammatory cytokines (pentoxifylline, PTX) and a well-known antioxidant, N-acetylcysteine (NAC), were evaluated on renal damage and oxidative stress following liver ischemia reperfusion (IR). Method: Five groups of six male rats were used. Group 1 was sham operated. In group 2, 90 min liver partial ischemia was induced by a clamp around both hepatic artery and portal vein and then followed by 4 h of reperfusion. In groups 3 and 4, PTX or NAC was injected intraperitoneally before the ischemia, while in group 5 both drugs were co-administered. The levels of alanine amino-transferase (ALT), aspartate amino-transferase (AST), blood urea nitrogen (BUN), and creatinine in serum as well as malonyldialdehyde (MDA) and glutathione (GSH) levels and morphological changes in renal tissues were assessed. Results: Significant increase in the serum levels of ALT and AST in IR group is indicative of liver functional damages. Elevated BUN and renal tissue MDA, decreased GSH levels, and morphological damages in IR group demonstrate a significant kidney injury and oxidative stress comparing to sham group. Administration of PTX alone and PTX + NAC prevented the IR-induced increase in renal MDA levels. Administration of both drugs and their co-administration prevented the reduction in renal GSH levels and morphological changes. Conclusion: Pretreatment with PTX and NAC before liver IR may be useful to ameliorate renal oxidative damage by preservation of cellular GSH concentration and a reduction in MDA levels. [ABSTRACT FROM AUTHOR]

Introduction: It has been demonstrated that peroxynitrite accompanies acute renal ischemia and contributes to the pathophysiology of renal damage. Therefore, we aimed to investigate the roles of N-acetylcysteine (NAC), a well-known powerful antioxidant, and ebselen (E), a scavenger of peroxynitrite, on renal injury induced by renal ischemia/reperfusion injury (IRI) of rat kidney. Materials and methods: Forty male Sprague--Dawley rats were divided into five groups: sham, renal IRI, renal IRI+NAC, renal IRI+E, and renal IRI+NAC+E. IR injury was induced by 60  min of bilateral renal ischemia followed by 6  h of reperfusion. After reperfusion, kidneys and blood samples were obtained for histopathological and biochemical evaluations. Results: Renal IR resulted in increased malondialdehyde and nitrite/nitrate levels suggesting increased lipid peroxidation and peroxynitrite production and decreased superoxide dismutase and glutathione peroxidase activities. Both NAC and E alone significantly decreased malondialdehyde and nitrite/nitrate levels and increased superoxide dismutase and glutathione peroxidase activities. Additionally in the renal IRI++NAC++E group, all biochemical results were quite close to those of sham group. Histopathologically, the kidney injury in rats treated with combination of NAC and E was found significantly less than the other groups. Conclusions: Both NAC and E are able to ameliorate IRI of the kidney by decreasing oxidative and nitrosative stresses and increasing free radical scavenger properties. Additionally, combination of NAC and E prevents kidney damage more than when each drug is used alone, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing renal IRI. [ABSTRACT FROM AUTHOR]

The beneficial effect of N-acetylcysteine (NAC) in the prevention of radiocontrast-induced nephropathy (RCIN) as well as the definition of an adequate surrogate parameter for the evaluation of the incidence of RCIN remain points of controversial discussion. Nearly all clinical studies used an increase in serum creatinine to define renal injury, although cystatin C is suggested to be superior to creatinine in estimating glomerular filtration rate (GFR). Furthermore, a recent study showed that in healthy volunteers, NAC leads to a decrease in serum creatinine without influencing serum cystatin C concentrations, implicating a possible overestimation of the protective effect of NAC on the incidence of RCIN. We compared serum creatinine and cystatin C levels in patients with chronic kidney disease undergoing coronary angiography, as these patients are to be considered at highest risk for the development of RCIN. A total of three doses of NAC was given orally, and patients received isotonic saline intravenously. Serum levels at baseline and 24 hours after angiography were not significantly different for serum creatinine (1.72 ± 0.08 mg/dl and 1.72 ± 0.08 mg/dl) and for cystatin C (1.72 ± 0.09 mg/dl and 1.76 ±0.10 mg/dl). There was a significant positive correlation between creatinine and cystatin C serum levels before and after exposure to radiocontrast medium ( p < 0.05) in all patients, including subgroup analyses. We conclude that serum creatinine and cystatin C are equivalent surrogate parameters for the evaluation of NAC in the prevention of RCIN. Furthermore, we present a prophylactic treatment regime easily applicable even in an outpatient setting, which seems to protect very effectively against RCIN in a high-risk group of patients. [ABSTRACT FROM AUTHOR]

Proinflammatory cytokines and hyperhomocysteinemia are associated with clinically relevant restenosis in coronary artery disease. N-acetylcysteine (NAC) can decrease proinflammatory cytokines and plasma homocystine as well as reduce contrast-induced nephropathy. The aim of this study, therefore, was to compare normal saline hydration with and without intravenous NAC in terms of changes in renal function, proinflammatory cytokines, inflammatory markers, and plasma total homocysteine during coronary angiography. Forty-six patients who underwent coronary angiography and/or stent implantation for unstable angina were enrolled and assigned to NAC or NS treatment groups based on normal saline hydration with or without intravenous NAC, respectively. The NS group had lower serum creatinine (Cre: p = 0.02) and plasma total homocysteine (tHcy; p < 0.001) and increased glomerular filtration rate (GFR; p = 0.003) after angiography. In the NAC group, the serum blood urea nitrogen (BUN; p = 0.001), Cre (p < 0.001), and plasma tHcy (p < 0.001) were lower, and the GFR (P = 0.013) was increased after angiography. There were no statistically significant differences in serum high-sensitivity C reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), or interleukin-10 (IL-10) before and after angiography in the NS and NAC groups. Intergroup comparison revealed that plasma tHcy level was lower for the NAC-treated patients (p = 0.002), with lower plasma tHcy level before and after treatment in this group (p < 0.001). Normal saline hydration can improve renal function and decrease plasma tHcy after coronary angiography with or without NAC; however, the combination of the two decreases plasma tHcy more than normal saline hydration alone. [ABSTRACT FROM AUTHOR]

Objectives. Cyclosporine A (CsA) is used for the treatment of autoimmune and inflammatory disorders. However, CsA-induced nephrotoxicity remains an important clinical problem, and oxidative stress has been implicated as a possible responsible mechanism. We assessed the protective ability of N-acetylcysteine (NAC), an antioxidant, against CsA-induced nephrotoxicity. Materials and Methods. Wistar albino rats were randomly assigned into four groups. Group 1 rats were treated with sodium chloride as control, group 2 with CsA, group 3 with CsA and NAC, and group 4 with NAC alone. Animals were sacrificed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (Cr), malondialdehyde (MDA) and nitric oxide (NO) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Kidney sections were analyzed for MDA and NO levels and SOD and GSH-Px activities, as well as histopathological changes. Results. Overall, the treatment of rats with CsA alone produced significant increases in NO and MDA levels and significant decreases in SOD and GSH-Px activities in serum and renal samples. Morphological changes, including tubular epithelial atrophy, vacuolizations, and cellular desquamations, were clearly observed in the rats treated with CsA alone. Concurrent NAC administration with CsA improved renal function, as indicated by lower BUN and Cr values. Moreover, NAC significantly reduced MAD and NO levels and increased SOD and GSH-Px activities in serum and renal tissue, as well as provided a histologically proven protection against CsA-induced nephrotoxicity. Conclusion. These results indicate that NAC produces a protective mechanism against CsA-induced nephrotoxicity and suggest a role for oxidative stress in pathogenesis. [ABSTRACT FROM AUTHOR]

Amikacin is a commonly used antibacterial drug that can cause significant nephrotoxic effects in both humans and experimental animals. It has been reported that one mechanism of the toxic effects of aminoglycoside antibiotics are the result of oxidative reactions. The aim of this study is to examine the effects of N-acetylcysteine, a thiol-containing antioxidant, on renal function (serum creatinine) and morphology (renal tubular damage) in mice subjected to amikacin-induced nephrotoxicity. A total of 32 mice were equally divided into four groups that were injected with either saline, amikacin (1.2g/kg intraperitoneally), N-acetylcysteine (150mg/kg intraperitoneally for three days) plus amikacin (1.2 g/kg intraperitoneally on the third day as a single dose), or N-acetylcysteine (150mg/kg intraperitoneally). Amikacin administration led to granulovacuolar tubular degeneration in light microscopic examination and myeloid bodies, mitochondrial electron-dense material deposition, and mitochondrial swelling in the proximal tubule epithelium in the electron microscopic evaluation. N-acetylcysteine administration before amikacin injection caused significant decreases in myeloid body and mitochondrial swelling and granulovacuolar tubular degeneration formation. Serum creatinine levels did not change as a result of any treatment. The results show that N-acetylcysteine has a protective effect on nephrotoxicity induced by amikacin. Higher doses of amikacin should be tried to observe biochemical effects. [ABSTRACT FROM AUTHOR]

Myoglobinuric acute renal failure has three pathogenic mechanisms: tubular obstruction, renal vasoconstriction, and oxidative stress. The latter is generated through the iron released from the group hemo of the myoglobin. Iron induces the formation of high-activity oxygen free radicals that increase oxidative stress and provoke lipid peroxidation and cellular death. This oxidative stress can be measured in several ways, both total or partially with the total antioxidant status or the intermediate enzymes. On the other hand, N-acetylcysteine is a demonstrated substance with antioxidant properties. The aim of the present work was to assess the effect of N-acetylcysteine on the oxidative stress in the glycerol-induced acute renal failure in rats model. We observed that the animals treated with N-acetylcysteine showed an improvement in the antioxidant activity given by an increase in the total antioxidant status and glutathione reductase levels in serum. This improvement was greater when treatment was administered before the induction of rhabdomyolysis. Nevertheless, the observed increase in antioxidant status was only statistically significant for glutathione reductase but not for total antioxidant status. Our results support an important role for N-acetylcysteine in the treatment of this form of acute renal failure, although we think that oxidative stress is not the main pathogenic mechanism of the tubular necrosis induced by rhabdomyolysis, tubular obstruction and renal vasoconstriction being still more important. [ABSTRACT FROM AUTHOR]

Oxygen metabolites play an important role in renal injury during myoglobinuric acute renal failure (ARF). This study was designed to determine the protective influence of N-acetylcysteine (NAC), a hydroxyl radical scavenger, and treatment in an experimental model of myoglobinuric-ARF induced by intramuscular injection of hypertonic glycerol in rats. The rats were randomly distributed into five groups: Group 0 (n = 10), was assigned to receive 2 mL saline (0,9%) intraperitoneally (ip); Group 1 (n = 10), NAC ip in a dose of 10 mg/100 g of body weight 30 min before the intramuscular (im) injection of 50% glycerol (10 mg/kg); Group 2 (n = 10), received saline 0,9% ip in a equivalent volume of NAC in Group 1 before the im injection of glycerol; Group 3 (n = 10), received NAC ip in a dose of 10 mg/100 g after im injection of glycerol; Group 4 (n = 10), saline 0,9% ip in a equivalent volume of NAC of the Group 3 after im administration of glycerol. After 24 h rats were sacrificed and kidney morphology and renal function were determined. A severe renal failure was produced by glycerol injection in the Groups 1, 2, 3, and 4, with significant tubular proximal necrosis and cast formation, and creatinine and urea concentrations were elevated in these groups without significant differences among groups, but Group 0 where the values were significantly lower. The results of this study suggests that ip administration of NAC in rats before or after glycerol injection do not confer protection against impairment of renal function under these conditions in this model of myoglobinuric-ARF. [ABSTRACT FROM AUTHOR]

N-acetylcysteine (NAC) repletes intracellular stores of reduced glutathione and may be a scavenger of oxygen free radicals. We report a 52-year-old female who developed acute renal insufficiency after administration of one dose of 150 mg of cisplatin for treatment of squamous cell cancer of the esophagus. Her blood urea nitrogen and creatinine rose from 12 and 0.7 mg/dL, respectively, to 24 and 1.8 mg/dL on day 5 after cisplatin. On that day the patient was begun on NAC, starting with a loading dose of 140-mg/kg-body weight followed by 70 mg/kg every 4 h for 4 days. Two days after starting NAC her renal function began to improve, and although she failed to complete a full course of the drug, by day 10 her serum creatinine had fallen to 0.8 mg/dL. A previous report showed that N-acetylcysteine might reverse cisplatin-induced renal toxicity. Our case supports this hypothesis. [ABSTRACT FROM AUTHOR]

Chloroform, a halogenated hydrocarbon, causes central nervous system (CNS) depression, cardiac arrhythmias, hepatotoxicity, and renal failure. We describe a successful outcome in a case of chloroform ingestion with renal and hepatotoxicity with N-acetylcysteine (NAC) administration and hemodialysis support. [ABSTRACT FROM AUTHOR]

Although acetaminophen (APAP)-associated liver injury is well recognized, there are few reports describing APAP nephrotoxicity, and most of them are single cases. It has also been suggested that N -acetylcysteine (NAC), used to treat the hepatotoxicity, may be harmful to the kidneys. To examine this contention and to determine whether renal involvement in APAP poisoning is at all common, we analyzed the incidence and outcome of acute renal dysfunction in patients hospitalized for APAP overdose reported to our regional poison center over a year. Eleven APAP-poisoned patients had elevated liver function tests; nine of them had azotemia. Those with higher AST levels tended to be younger and to have lower APAP levels on admission. Two patients with acute renal injury died after admission. The other seven patients with renal dysfunction recovered in 2 to 7 days. Six of these received NAC; their mean serum creatinine fell from 3.2 ± 2.0 versus 1.7 ± 0.9 mg/dL ( p [ABSTRACT FROM AUTHOR]

Contrast-induced nephropathy is reported to be the third leading cause of acute renal failure. The development of contrast-induced nephropathy is associated with prolonged hospitalization, the potential need for renal replacement therapy, and increased mortality. N-acetylcysteine is commonly used for the prevention of contrast-induced nephropathy despite inconsistent results from numerous clinical trials and meta-analyses. The advantage of N-acetylcysteine in most studies was based on a decrease in the serum creatinine concentration and a decrease in oxidative stress. N-acetylcysteine itself can directly lower serum creatinine concentration without improving renal function, and hypovolemia can affect the oxidative stress. In most of the N‐acetylcysteine studies, there are a lack of volume status and secondary end points. The value of N-acetylcysteine for the prevention of contrast-induced nephropathy seems questionable. The interactions between serum creatinine, N-Acetylcysteine, volume status, and the development of contrast-induced nephropathy were discussed in this letter. [ABSTRACT FROM AUTHOR]