thymic-factor--circulating and Proteinuria

Serum thymic factor (FTS), a thymic peptide hormone, has been reported to increase superoxide disumutase (SOD) levels in senescence-accelerated mice. In the present study, we examined the effect of FTS on cephaloridine (CER)-induced nephrotoxicity in vivo and in vitro. We previously reported that CER led to extracellular signal-regulated protein kinase (ERK) activation in the rat kidney. So, we also investigated whether FTS has an effect on ERK activation induced by CER. Treatment of male Sprague-Dawley rats with intravenous CER (1.2 g/kg) for 24 h markedly increased BUN and plasma creatinine levels and urinary excretion of glucose and protein, decreased creatinine clearance and also led to marked pathological changes in the proximal tubules, as revealed by electron micrographs. An increase in phosphorylated ERK (pERK) was detected in the nuclear fraction prepared from the rat kidney cortex 24 h after CER injection. Pretreatment of rats with FTS (50 microg/kg, i.v.) attenuated the CER-induced renal dysfunction and pathological damage. FTS also suppressed CER-induced ERK activation in the kidney. In vitro treatment of the established cell line, LLC-PK1 cells, with FTS significantly ameliorated CER-induced cell injury, as measured by lactate dehydrogenase (LDH) leakage. Our results, taken together with our previous report that MEK inhibitors ameliorated CER-induced renal cell injury and ERK activation induced by CER, suggest that FTS participates in protection from CER-induced nephrotoxicity by suppressing ERK activation induced by CER.

Topics: Animals; Blotting, Western; Cell Nucleus; Cephaloridine; Cephalosporins; Creatinine; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Kidney; Kidney Diseases; L-Lactate Dehydrogenase; LLC-PK1 Cells; Male; Microscopy, Electron; Mitogen-Activated Protein Kinases; Phosphorylation; Proteinuria; Rats; Rats, Sprague-Dawley; Swine; Thymic Factor, Circulating

In this study we have evaluated the action of two compounds, cyclosporin A (Cy A) and thymulin (FTS-Zn) in old (NZB X NZW) F1 male mice which develop severe autoimmune disease. Compared with control mice, thymulin and Cy A treated mice already showed by 2 weeks a dramatic diminution of their anti-DNA antibody level which remained low throughout the treatment period and persisted for 7 weeks afterwards. Renal specimens were studied by direct immunofluorescence in Cy A and thymulin treated mice. Glomerular deposits were decreased compared with control mice; these differences were particularly clearcut for IgG1 and IgG2 deposits. Finally, thymulin (FTS-Zn) and Cy A appeared to induce the same improvement of DNA titres and glomerulopathy in (NZB X BW) F1 mice.

Topics: Animals; Antibodies, Antinuclear; Autoimmune Diseases; Cyclosporins; DNA; Fluorescent Antibody Technique; Glomerulonephritis; Immunoglobulin G; Kidney Glomerulus; Male; Mice; Mice, Inbred NZB; Proteinuria; Thymic Factor, Circulating; Thymus Hormones