vitamin-b-12 and Nephritis

Tamoxifen (TAMO) is a chemotherapeutic drug used for the treatment of breast cancer. Nevertheless, there is a lack of information available in regarding its nephrotoxicity. The purpose of this work was to investigate the impact of cyanocobalamin (COB) and/or calcitriol (CAL) injections on TAMO-induced nephrotoxicity.. Animals were allocated into five groups as follows: normal control group; TAMO (45 mg/kg) administered group; TAMO+COB (6mg/kg, i.p) treated group; TAMO+CAL (0.3 μg/kg, i.p) treated group; TAMO+COB+CAL combination groups.. Renal injury induced by TAMO was confirmed by the alteration in renal function parameters in the serum (urea and creatinine), as well as in the urine (creatinine clearance, total protein and albumin). These results were supported by histopathological examination. Upregulation of renal inflammatory parameters; tumor necrosis factor (TNF)-α, interleukin (IL)-6, C-reactive protein (CRP); and transforming growth factor (TGF)-β1 as well as in protein expression of nuclear factor-kappa B (NF-κB) and cleaved caspase-3 were observed to a greater extent in the TAMO-treated rats compared with the control. Renal fibrosis was also evidenced by a elevation in renal L-hydroxyproline level as well as by histomorphological collagen deposition in TAMO-treated groups compared to the control group. Administration of COB and/or CAL concurrently with TAMO significantly ameliorated the deviation in the above-studied parameters and improved the histopathological renal picture.. Inhibition of NF-κβ-mediated inflammation and caspase-3-induced apoptosis are possible renoprotective mechanisms of COB and/or CAL against TAMO nephrotoxicity, which was more noticeable in the TAMO group treated with the combination of the two vitamins in question.

Topics: Acute Kidney Injury; Animals; Apoptosis; Blood Urea Nitrogen; Calcitriol; Caspase 3; Creatinine; Female; Kidney; Kidney Diseases; Kidney Function Tests; Nephritis; NF-kappa B; Rats; Rats, Wistar; Signal Transduction; Tamoxifen; Tumor Necrosis Factor-alpha; Vitamin B 12

Classical (or isolated) methylmalonic acidemia (MMA) is a heterogeneous inborn error of metabolism most typically caused by mutations in the vitamin B12-dependent enzyme methylmalonyl-CoA mutase (MUT). With the improved survival of individuals with MMA, chronic kidney disease has become recognized as part of the disorder. The precise description of renal pathology in MMA remains uncertain.. Light microscopy, histochemical, and ultrastructural studies were performed on the native kidney obtained from a 19-year-old patient with mut MMA who developed end stage renal disease and underwent a combined liver-kidney transplantation.. The light microscopy study of the renal parenchyma in the MMA kidney revealed extensive interstitial fibrosis, chronic inflammation, and tubular atrophy. Intact proximal tubules were distinguished by the widespread formation of large, circular, pale mitochondria with diminished cristae. Histochemical preparations showed a reduction of cytochrome c oxidase and NADH activities, and the electron microscopy analysis demonstrated loss of cytochrome c enzyme activity in these enlarged mitochondria.. Our results demonstrate that the renal pathology of MMA is characterized by megamitochondria formation in the proximal tubules in concert with electron transport chain dysfunction. Our findings suggest therapies that target mitochondrial function as a treatment for the chronic kidney disease of MMA.

Topics: Amino Acid Metabolism, Inborn Errors; Atrophy; Diet, Protein-Restricted; Female; Humans; Kidney; Kidney Diseases; Kidney Tubules, Proximal; Metabolism, Inborn Errors; Methylmalonyl-CoA Mutase; Mitochondria; Mitochondrial Diseases; Nephritis; Vitamin B 12; Young Adult

Topics: Acute Kidney Injury; Biological Assay; Blood Chemical Analysis; Glomerulonephritis; Kidney Diseases; Kidneys, Artificial; Mercury Poisoning; Nephritis; Nephritis, Interstitial; Postoperative Complications; Pyelonephritis; Renal Insufficiency; Solvents; Toxicology; Tuberculosis; Tuberculosis, Renal; Vitamin B 12; Wounds and Injuries

The serum vitamin B(12) level was abnormally high in 14 out of 32 cases of renal failure. This was probably due to impaired excretion of the vitamin, but the results of measurements of the rate of excretion of radioactive vitamin B(12) did not provide unequivocal evidence on this point; other possible explanations are discussed. Renal failure must be added to the causes of high serum B(12) levels.

Topics: Arteriosclerosis; Glomerulonephritis; Humans; Hypertension; Hypertension, Malignant; Kidney; Kidney Diseases; Nephritis; Nephrocalcinosis; Polycystic Kidney Diseases; Pyelonephritis; Renal Insufficiency; Vitamin B 12