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Effect of probucol on mRNA expression of glomerular antioxidant enzymes in rat with subtotal nephrectomy
1Department of Nephrology, Jinling Hospital, School of Medicine, Nanjing University.
Objective:
To investigate 1) the glomerular mRNA expression and protein activity of antioxidant enzymes (AOEs) including superoxide dismutase (SOD) and glutathine peroxidase (GSH-Px) and the glomerular content of lipid peroxide-malondiadehyde (MDA), 2) the effects of probucol (P), a potent antioxidant agent on these AOEs and MDA levels, in the chronic phase of subtotal nephrectomized rats.
Methods:
The adult male Spregue-Dawley rats were randomly divided into three groups at the first week after subtotal renal ablation. Group 1 was sham rats (sham n = 8), group 2 underwent 5/6 nephrectomy without special therapy (5/6 Nx n = 8), and group 3 with 5/6 nephrectomy received probucol (5/6 Nxs+P n = 8) at a dose of 1% in the rat chow. At the 12th week after P was administrated, all of the rats were sacrificed to remove left kidney for the determination of glomerular level of MDA, activity of SOD, and GSH-Px, glomerular mRNA expression of AOEs by Northern blot analysis as well as a histological examination.
Results:
In 5/6 Nx, serum cholesterol, proteinuria increased and creatinine clearance decreased progressively with age as compared with that in sham. Those abnormalities as well as glomerulosclerosis index (GI) ameliorated with the administration of probucol at the 12th week after subtotal nephrectomy [GI: sham 3.12 +/- 1.20, P < 0.01 vs 5/6 Nx 5/6 Nx 188.6 +/- 25.1; 5/6 Nx +/- P, 106.9 +/- 17.6, P < 0.05 vs 5/6 Nx]. The probucol therapy also significantly improved the decrease of glomerular Mn-SOD and GSH-Px both at mRNA level and protein activity and the increase of glomerular MDA content.
Conclusions:
We demonstrated a deficiency of glomerular AOEs in the chronic phase of remnant kidney, which may contribute to the progression of renal injury. The protective effects of probucol on both renal functional impairment and the development of glomerulosclerosis may be partially associated with improving surviving glomerular AOEs.
Insights
Glomerular antioxidant enzymes (AOEs) are deficient in chronic kidney disease, contributing to injury. Probucol treatment improved renal function and reduced glomerulosclerosis by enhancing AOEs.
Area of Science:
- Nephrology
- Biochemistry
- Pharmacology
Background:
- Chronic kidney disease is associated with oxidative stress and impaired antioxidant defenses.
- Glomerular antioxidant enzymes (AOEs) play a crucial role in protecting the kidney from oxidative damage.
- Subtotal nephrectomy in rats is a model for studying chronic kidney disease progression.
Purpose of the Study:
- To investigate glomerular antioxidant enzyme (AOE) mRNA expression and protein activity, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels in subtotal nephrectomized rats.
- To evaluate the effects of probucol, a potent antioxidant, on these parameters in the chronic phase of kidney injury.
Main Methods:
- Adult male Sprague-Dawley rats underwent 5/6 subtotal nephrectomy or sham surgery.
- Rats were divided into nephrectomized (5/6 Nx) and nephrectomized plus probucol (5/6 Nx+P) groups.
- Glomerular MDA content, SOD and GSH-Px activity, and AOE mRNA expression were analyzed at 12 weeks.
Main Results:
- Subtotal nephrectomy led to increased serum cholesterol, proteinuria, and glomerulosclerosis index (GI), with decreased creatinine clearance.
- Probucol treatment significantly ameliorated these abnormalities, reducing GI and improving renal function.
- Probucol therapy also improved the decrease in glomerular Mn-SOD and GSH-Px (mRNA and activity) and the increase in MDA content.
Conclusions:
- A deficiency in glomerular antioxidant enzymes (AOEs) occurs in the chronic phase of remnant kidney disease, potentially driving renal injury progression.
- Probucol demonstrates protective effects against renal functional impairment and glomerulosclerosis development.
- These protective effects may be partly attributed to the improvement of glomerular AOE levels by probucol.