flavin-adenine-dinucleotide and Kidney-Diseases

The kidney is one of the most radiosensitive organs; it is the primary dose-limiting organ in radiotherapies for upper abdominal cancers. The role of mitochondrial redox state in the development and treatment of renal radiation injury, however, remains ill-defined. This study utilizes 3D optical cryo-imaging to quantify renal mitochondrial bioenergetics dysfunction after 13 Gy leg-out partial body irradiation (PBI). Furthermore, the mitigating effects of lisinopril (lisino), an anti-hypertensive angiotensin converting enzyme inhibitor, is assessed in renal radiation-induced injuries. Around day 150 post-irradiation, kidneys are harvested for cryo-imaging. The 3D images of the metabolic indices (NADH, nicotinamide adenine dinucleotide, and FAD, flavin adenine dinucleotide) are acquired, and the mitochondrial redox states of the irradiated and irradiated + lisino kidneys are quantified by calculating the volumetric mean redox ratio (NADH/FAD). PBI oxidized renal mitochondrial redox state by 78%. The kidneys from the irradiated + lisino rats showed mitigation of mitochondrial redox state by 93% compared to the PBI group. The study provides evidence for an altered bioenergetics and energy metabolism in the rat model of irradiation-induced kidney damage. In addition, the results suggest that lisinopril mitigates irradiation damage by attenuating the oxidation of mitochondria leading to increase redox ratio.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Female; Flavin-Adenine Dinucleotide; Gamma Rays; Imaging, Three-Dimensional; Kidney; Kidney Diseases; Lisinopril; Mitochondria; NAD; Radiation Injuries; Rats

We describe an infant girl with a clinical, chemical, and pathologic syndrome remarkably similar to Zellweger cerebrohepatorenal syndrome but whose liver parenchymal cells contained abundant peroxisomes. Peroxisomal L-alpha hydroxy acid oxidase, catalase, and the plasmalogen synthesizing enzyme dihydroxy acetone phosphate-acyl transferase activities were normal; other peroxisomal enzymatic activities, including fatty acyl-CoA oxidase and D-amino acid oxidase, were reduced by 80% to 85%. Oxidation of bile acids and pipecolic acid was also deficient. Autopsy revealed the presence of neuronal heterotopia, renal cortical cysts, adrenal atrophy, and accumulation of very long chain fatty acids. The clinical and pathologic features of this case of "pseudo-Zellweger syndrome" reflect a deficiency in multiple peroxisomal activities rather than a defect in peroxisomal biogenesis. The deficient enzymatic activities require flavin adenine dinucleotide, and the underlying defect may be in the utilization of this cofactor.

Topics: Acyl-CoA Oxidase; Bile Acids and Salts; Brain Diseases; D-Amino-Acid Oxidase; Diagnosis, Differential; Female; Flavin-Adenine Dinucleotide; Humans; Infant; Kidney Diseases; Liver; Liver Diseases; Microbodies; Mitochondria, Liver; Muscles; Oxidoreductases; Syndrome

Topics: Female; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Flavins; Humans; Kidney; Kidney Diseases; Liver; Liver Cirrhosis; Liver Diseases; Male; Nutrition Surveys; Proteins; Riboflavin; Vitamins

Topics: Adolescent; Adult; Carbohydrate Metabolism, Inborn Errors; Carbon Isotopes; Child; Coenzymes; Dialysis; Erythrocytes; Female; Flavin-Adenine Dinucleotide; Freezing; Glyoxylates; Humans; In Vitro Techniques; Kidney Diseases; Leukocytes; Male; Methods; NAD; Oxalates; Oxidation-Reduction; Ultrasonics

Topics: Adenine; Adenine Nucleotides; Adenosine Triphosphate; Animals; Flavin-Adenine Dinucleotide; Kidney; Kidney Diseases; Nucleosides; Puromycin Aminonucleoside; Rats

Topics: Adenine; Adenine Nucleotides; Adenosine Triphosphate; Animals; Coenzymes; Flavin-Adenine Dinucleotide; Kidney; Kidney Diseases; Nucleosides; Nucleotides; Puromycin Aminonucleoside; Rats