Heat shock protein 70 induction and its urinary excretion in a model of acetaminophen nephrotoxicity

Abstract

Acetaminophen (APAP) is an analgesic-antipyretic drug widely used in children. In the present study, we used an in vivo model of APAP-induced nephrotoxicity in male Wistar rats. We analyzed whether toxic doses of APAP could induce heat shock protein 70 (HSP70) in the kidney and whether HSP70 could be detected in urine. Renal function and histological evaluation of the kidneys were performed at different times after APAP administration (1,000 mg/kg body weight i.p.). Cellular injury was assessed by Triton X-100 solubilization of Na(+)/K(+) ATPase. Renal and hepatic glutathione levels were also measured. Urinary N-acetyl-beta-D glucosaminidase (NAG) excretion increased 4 h after intoxication. At this time, urea and creatinine were at control levels and a slight degree of histological alteration was detected. Kidney microscopic evaluation, Na(+)/K(+) ATPase solubility, creatinine, and urea levels and NAG excretion did not differ from those of controls 48 h after APAP administration. HSP70 was detected in urine obtained from 4 to 24 h after APAP administration. HSP70 abundance in renal cortex was increased at early time points and 48 h after APAP administration. Urinary HSP70 excretion would be a marker of its renal induction combined with the loss of tubule integrity. NAG would be a suitable early biomarker of APAP-induced nephrotoxicity.

Higher urine heat shock protein 70/creatinine ratio in type 1 diabetes mellitus

“…The authors advocate that HSP70 in urine derived from renal cells according to their findings. In addition, there was no relationship between uHSP70/ Cr and HbA1c in our study as well as the study of Calabrese et al 29 In another study, Molinas et al 31 evaluated HSP70 levels in urine, kidney and liver samples of the rats receiving acetaminophen which led to hepatic and renal toxicity. The authors found that HSP70 levels increased in renal cortical tissue and in urine simultaneously, although HSP70 levels in liver tissue did not increase despite the elevation of plasma ALT levels.…”

Urine heat shock protein 70 levels as a marker of urinary tract infection in children

“…These authors concluded that this increase might be related to HSP70 secretion from the tumor cells to urine [20]. Molinas et al [21] investigated HSP70 levels in urine, kidney and liver samples of rats receiving acetaminophen, which caused hepatic and renal toxicity. These authors reported that HSP70 levels increased in the urine and in renal cortex simultaneously, whereas HSP70 levels in liver tissue did not increase despite the elevation of plasma alanine transaminase levels suggesting hepatic damage [21].…”

“…Molinas et al [21] investigated HSP70 levels in urine, kidney and liver samples of rats receiving acetaminophen, which caused hepatic and renal toxicity. These authors reported that HSP70 levels increased in the urine and in renal cortex simultaneously, whereas HSP70 levels in liver tissue did not increase despite the elevation of plasma alanine transaminase levels suggesting hepatic damage [21]. In their study of six pediatric transplant patients, Mueller et al [22] found that uHSP72 levels increased during the first 12 h after renal transplantation.…”

“…Only a few studies have reported that uHSP70 levels increase in other kidney or bladder diseases [20][21][22][23]. In their search for biomarkers for the diagnosis and staging of bladder cancer, Margel et al [20] reported that uHSP70 levels were increased in patients with bladder cancer.…”

Cerebrospinal fluid levels of extracellular heat shock protein 72: A potential biomarker for bacterial meningitis in children

“…While classically considered an intracellular protein, many studies over the last several years have found that Hsps can also be present in the extracellular compartment. Clinical studies have documented Hsps in a variety of disorders in almost every extracellular fluid examined to date, including serum, plasma [10], urine [11,12], bronchoalveolar lavage fluid [13], amniotic fluid [14], and cerebrospinal fluid (CSF) [15]. For example, serum levels of the 72 kDa Hsp (Hsp72) are increased in critically ill patients following trauma and severe sepsis [10,16,17].…”