Expressions of Protein Oxidation Markers, Dityrosine and Advanced Oxidation Protein Products in Cisplatin-Induced Nephrotoxicity in Rats

Abstract

ABSTRACT. The purpose of this study was to evaluate whether dityrosine and advanced oxidation protein products (AOPP) reflect the severity of cisplatin-induced nephrotoxicity. Immunoexpression of dityrosine in kidneys and plasma AOPP concentration were examined up to day 4 post-cisplatin injection in rats. Cisplatin injection induced tubular injury on days 2-4 after injection and increased serum creatinine and BUN on days 3 and 4. On days 2-4, dityrosine was immunostained in the cytoplasm of damaged tubular cells, and their immunostaining intensity increased time-dependently. Plasma AOPP levels were significantly increased on days 3 and 4. These results suggest that expressions of dityrosine and AOPP were associated with the severity of renal injury and may be useful markers for the development of cisplatin-induced nephrotoxicity.KEY WORDS: advanced oxidation protein product, cisplatin, dityrosine, nephrotoxicity, oxidative stress.

Protective Effect of Lactoferrin on Cisplatin-Induced Nephrotoxicity in Rats

“…treatment ( Table 1). As reported in the previous study [14], the tubular damages occurred at 48 hr after cisplatin treatment. The Pt contents in the cisplatin alone and the cisplatin+bLf groups were 16.70 ± 1.96 and 9.8 ± 2.1 µg/g tissue, respectively ( Table 1).…”

“…It is well known that cisplatin administered to rats damages the proximal tubule [2,4,14,16,19,21] and that the kidney injury induced by cisplatin is similar to ischemic damage [6,29]. The acute renal failure caused by cisplatin is typically characterized by signs such as a severe reduction in the glomerular filtration rate (GFR) [24], a variable fall in the renal blood flow [6,29], a decrease in urinary concentrating ability and changes in urine volume and creatinine clearance [20].…”

Expressions of Protein Oxidation Markers, Dityrosine and Advanced Oxidation Protein Products in Acetaminophen-Induced Liver Injury in Rats

“…The evidence that dityrosine was found in the different types of protein after exposed to a variety of oxidants may support more availability of its use as a protein oxidation marker [10]. Dityrosine has been detected in diverse pathological situations in humans [16] and experimental animals [1,8,17,19,22,32]. Dityrosine was detected immunohistochemically in lipofuscin of pyramidal neurons of aged human brains [16], atherosclerotic lesions of apolipoprotein E-deficient mice [17] and cholesterol-fed rabbits [8], and in renal tubular lesions in rat treated with cisplatin [19].…”

“…Dityrosine has been detected in diverse pathological situations in humans [16] and experimental animals [1,8,17,19,22,32]. Dityrosine was detected immunohistochemically in lipofuscin of pyramidal neurons of aged human brains [16], atherosclerotic lesions of apolipoprotein E-deficient mice [17] and cholesterol-fed rabbits [8], and in renal tubular lesions in rat treated with cisplatin [19]. The dityrosine concentration significantly increased in the liver of rats chronically intoxicated with ethanol [1], cardiac and skeletal muscle proteins in aging mice [22] and cooking-oil fume-induced acute lung injury in rats [32].…”

“…Increase of plasma or serum AOPP concentration has been observed in various pathological situations related to oxidative stress in humans and experimental animals, peritoneal dialysis [20], obese children [29], chronic diabetic in rats [18], cisplatin-induced nephrotoxicity in rats [19] and protein malnutrition in mice [30]. In the present study, plasma AOPP levels were higher in rats examined in the later period of the study and were well comparable to the severity of hepatotoxicity, suggesting that plasma AOPP levels may be useful as an oxidative stress marker for monitoring the development of APAP-induced liver injury.…”