harmine and Kidney-Diseases

Topics: Animals; Down-Regulation; Epithelial Cells; Fatty Acids; Fibrosis; Harmine; Kidney; Kidney Diseases; Mice

The renal toxicity of harman and norharman, administered for 2 or 4 weeks at dietary levels of 1,000, 500, or 0 parts per million (ppm), was investigated in 6-week-old male F344/DuCrj rats. Although rats fed 1,000 ppm harman or norharman, but not the 500 ppm level, demonstrated marked body weight retardation from 1 week to termination, no mortalities occurred. Marked elevation of water consumption was evident in rats given harman or norharman at 1,000 ppm, but not at 500 ppm, together with large increases in urine of low specific gravity. Urinary lysosomal enzymes (N-acetyl-beta-D-glucosaminidase, NAG, and lactate dehydrogenase, LDH) and sugar levels were increased, and the brush border enzymes (gamma-glutamyl transpeptidase, GGT, and alkaline phosphatase, ALP) decreased. Furthermore, serum biochemistry revealed clear elevation of parameters indicating renal toxicity in these rats. Histopathologically, rats fed 1,000 ppm harman or norharman, but not 500 ppm, demonstrated focal toxic renal degenerative/necrotic and regenerative lesions in proximal, distal, and collecting tubules. These changes were associated with a clearly increased labeling index (LI) of the nuclei of renal tubular epithelial cells on immunohistochemical staining for 5-bromo-2'-deoxyuridine (BrdU). Chemical specific crystal formation within tubular lumina was evident in rats fed 1,000 ppm, but not 500 ppm, this being considered the cause of the renal tubular lesions. It was concluded that harman and norharman exert renal toxicity at the dietary level of 1,000 ppm, but not 500 ppm, in male F344 rats.

Topics: Acetylglucosamine; Animals; Bromodeoxyuridine; Carbolines; DNA; Drinking; Harmine; Kidney Diseases; Kidney Tubules; L-Lactate Dehydrogenase; Male; Microvilli; Organ Size; Phagocytosis; Rats; Rats, Inbred F344; Urination

The carcinogenic effects of aniline and norharman given alone or in combination were examined in rats. Neoplastic changes including hyperplastic changes of the urinary bladder were not found in all groups. Papillomas of forestomach were observed in 5 rats out of 110 rats. However, this was not significantly different among the groups. Pyelonephritis or chronic nephritis were also seen in all groups. Hematological and blood biochemical analysis did not show any notable difference in the animals treated with aniline and/or norharman.

Topics: Alkaloids; Aniline Compounds; Animals; Carbolines; Carcinogens; Harmine; Kidney Diseases; Male; Papilloma; Pituitary Neoplasms; Rats; Stomach Neoplasms; Urinary Bladder Neoplasms