Immunohistochemical Analysis of 4-HNE, NGAL, and HO-1 Tissue Expression after Apocynin Treatment and HBO Preconditioning in Postischemic Acute Kidney Injury Induced in Spontaneously Hypertensive Rats

Abstract

Oxidative stress has been considered as a central aggravating factor in the development of postischemic acute kidney injury (AKI). The aim of this study was to perform the immunohistochemical analysis of 4-hydroxynonenal (4-HNE), neutrophil gelatinase-associated lipocalin (NGAL), and heme oxygenase-1 (HO-1) tissue expression after apocynin (APO) treatment and hyperbaric oxygenation (HBO) preconditioning, applied as single or combined protocol, in postischemic acute kidney injury induced in spontaneously hypertensive rats (SHR). Twenty-four hours before AKI induction, HBO preconditioning was carried out by exposing to pure oxygen (2.026 bar) twice a day, for 60 min in two consecutive days. Acute kidney injury was induced by removal of the right kidney while the left renal artery was occluded for 45 min by atraumatic clamp. Apocynin was applied in a dose of 40 mg/kg body weight, intravenously, 5 min before reperfusion. We showed increased 4-HNE renal expression in postischemic AKI compared to Sham-operated (SHAM) group. Apocynin treatment, with or without HBO preconditioning, improved creatinine and phosphate clearances, in postischemic AKI. This improvement in renal function was accompanied with decreased 4-HNE, while HO-1 kidney expression restored close to the control group level. NGAL renal expression was also decreased after apocynin treatment, and HBO preconditioning, with or without APO treatment. Considering our results, we can say that 4-HNE tissue expression can be used as a marker of oxidative stress in postischemic AKI. On the other hand, apocynin treatment and HBO preconditioning reduced oxidative damage, and this protective effect might be expected even in experimental hypertensive condition.

Functional consequence of myeloid ferritin heavy chain on acute and chronic effects of rhabdomyolysis-induced kidney injury

“…We also corroborated previous reports that identified maximal expression of 4-HNE, a product of lipid peroxidation in the tubular epithelium and to a lesser extent in the glomeruli and interstitial cells ( 8 , 24 ). This is in contrast with a recent report that found marked expression of 4-HNE only in the glomerulus and interstitium of hypertensive rats that underwent ischemia reperfusion injury ( 41 ). We speculate that the expression pattern is reflective of the site of maximal injury, which is predominantly tubular epithelium during rhabdomyolysis.…”

Mercuric Chloride Induced Nephrotoxicity: Ameliorative Effect of Carica papaya Leaves Confirmed by Histopathology, Immunohistochemistry, and Gene Expression Studies

“…The chelating property of ECP reduces the expression of NGAL by modulating the concentration of HgCl 2 and increasing the antioxidant levels, which prevent renal damage. The findings of this study are similar with those of Kovacevic et al (2021) and Quan et al (2020) that showed reduced immunohistochemical expression of NGAL in the tubules of kidney in the treatment with apocynin and aristolochic acid, respectively. − Similarly, a study by Huang et al observed reduced expression of NGAL with the treatment of Cordyceps cicadae in hypertensive renal injury …”

“…In this study, rats treated with HgCl 2 showed remarkable expression of NGAL in the cytoplasm of proximal tubules and glomerulus indicating renal damage, which was previously noticed in the acute kidney injury, gentamicin, cisplatin-induced nephrotoxic model. 46,60,88 Similarly, positive expression of NGAL in immunohistochemistry was observed in contrastinduced nephropathy rats and ischemia−reperfusion kidney injury. The expression of NGAL in the proximal convoluted tubules is due the depletion of adenosine triphosphate from the mitochondria.…”

Immunohistochemical expression of apolipoprotein B and 4-hydroxynonenal proteins in colorectal carcinoma patients: a retrospective study

“…It modifies DNA and binds to proteins to form 4HNE protein adducts, which act as growth-regulating signaling factors and cause inflammation and apoptosis ( 11 , 12 ). 4HNE expression was decreased following apocynin treatment and hyperbaric oxygenation in acute kidney injury ( 13 ). However, it was increased in non-alcoholic fatty liver disease ( 11 ) and in Barrett's esophagus with specific intestinal metaplasia compared with esophageal cancer ( 14 ).…”