cytochrome-c-t and Renal-Insufficiency--Chronic

Apoptosis is closely interconnected with the severity of renal injury. Magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix showed a wide range of renoprotective effects. However, the underlying mechanisms under beneficial effects have not been elucidated. This study was conducted to investigate whether MLB could mediate renal protection and attenuate apoptosis by mitochondrial pathway. In the present study, the rat model of chronic renal failure (CRF) was established by the 5/6 renal ablation/infarction (A/I) operation. 28 days after the surgery, 30 rats were randomly divided into three groups: sham group, 5/6 (A/I) group and 5/6 (A/I) + MLB group. After 56 days of treatment, we detected the severity of kidney injury, the degree of mitochondrial bax oligomerization and cytochrome c release along with the expression of P53 protein. Our results showed that MLB markedly attenuated kidney injury and apoptosis in 5/6 (A/I) model rats with CRF. MLB effectively inhibited mitochondrial bax accumulation and release of cytochrome c into the cytosol and down-regulated the levels of p53 phosphorylation and acetylation. These data showed that MLB could contribute to renal protection by inhibiting mitochondrial pathway of apoptosis.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Cytochromes c; Cytosol; Disease Models, Animal; Drugs, Chinese Herbal; Kidney; Male; Mitochondria; Protein Multimerization; Rats, Sprague-Dawley; Renal Insufficiency, Chronic; Tumor Suppressor Protein p53

Extensive structural damage within the kidney must be present before serum creatinine increases. However, a subclinical phase of chronic kidney disease (CKD) usually goes undetected. Here we tested whether experimental subclinical CKD would modify functional and damage biomarker profiles of acute kidney injury (AKI). Subclinical CKD was induced in rats by adenine or aristolochic acid models but without increasing serum creatinine. After prolonged recovery (three to six weeks), AKI was induced with a subnephrotoxic dose of cisplatin. Urinary levels of kidney injury molecule-1 (KIM-1), cytochrome C, monocyte chemotactic protein-1 (MCP-1), clusterin, and interleukin-18 increased during CKD induction, without an increase in serum creatinine. After AKI in adenine-induced CKD, serum creatinine increased more rapidly, while increased urinary KIM-1, clusterin, and MCP-1 were delayed and reduced. Increased serum creatinine and biomarker excretion were associated with diffuse tubulointerstitial injury in the outer stripe of outer medulla coupled with over 50% cortical damage. Following AKI in aristolochic acid-induced CKD, increased serum creatinine, urinary KIM-1, clusterin, MCP-1, cytochrome C, and interleukin-18 concentrations and excretion were greater at day 21 than day 42 and inversely correlated with cortical injury. Subclinical CKD modified functional and damage biomarker profiles in diametrically opposite ways. Functional biomarker profiles were more sensitive, while damage biomarker diagnostic thresholds and increases were diminished and delayed. Damage biomarker concentrations and excretion were inversely linked to the extent of prior cortical damage. Thus, thresholds for AKI biomarkers may need to be lower or sampling delayed in the known presence of CKD.

Topics: Acute Kidney Injury; Adenine; Animals; Aristolochic Acids; Biomarkers; Cell Adhesion Molecules; Chemokine CCL2; Cisplatin; Clusterin; Creatinine; Cytochromes c; Disease Models, Animal; Humans; Interleukin-18; Kidney; Kidney Function Tests; Osteopontin; Rats; Rats, Sprague-Dawley; Renal Elimination; Renal Insufficiency, Chronic