N-acetylcysteine protects against star fruit-induced acute kidney injury

Abstract

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.

The Role of Oxidative Stress and Inflammation in Acute Oxalate Nephropathy Associated With Ethylene Glycol Intoxication

“…In summary, we describe the presence of increased renal oxidative stress, evidence of activated necroptotic pathways, and renal inflammation in a patient with acute oxalate nephropathy secondary to ethylene glycol intoxication. Our findings are the first to translate previous animal and cell line studies 2 , 3 , 5 , 6 into humans, and suggest a shared pathogenic mechanism of renal CaOx deposition, increased oxidative stress, inflammation, and necroptosis.…”

“…Calcium oxalate crystal (CaOx) deposition within the renal parenchyma is well described as a cause of both acute kidney injury and chronic kidney disease. Animal and cell line studies have previously demonstrated that this injury is modulated by oxidative stress−induced danger-associated molecular patterns following CaOx deposition within the interstitium 1 , 2 . It has been postulated that these oxidative stress-induced danger-associated molecular patterns may participate in the pathogenesis of acute kidney injury and chronic kidney disease in humans, leading to the recruitment of an inflammatory response characterized by an increased infiltration of monocytes and macrophages.…”

N-Acetylcysteine Ameliorates Gentamicin-Induced Nephrotoxicity by Enhancing Autophagy and Reducing Oxidative Damage in Miniature Pigs

“…In addition, the genetic integrity and uniformity of the population is maintained. The animals were placed in individual metabolic cages and divided into 3 experimental groups, according to previous studies (21, 22). Pigs in the control group (CON; n = 6) received a daily intramuscular (i.m.)…”

Star fruit nephrotoxicity: a case series and literature review

“…Recently the effect of N- acetyl cysteine (NAC) on star fruit induced acute kidney injury was studied in animal models. The results suggest that NAC may attenuate renal dysfunction by means of reducing oxidative stress, oxaluria and inflammation [ 39 ].…”