Determination of rat β₂‐microglobulin in urine and in serum. II. Application of its urinary measurement to selected nephrotoxicity models

Abstract

beta 2-microglobulin (beta 2-m) was measured in the urine of rats by a specific immunoassay based on latex particles agglutination. The excretion of this protein was compared to the excretion of the enzyme beta-N-acetyl-D-glucosaminidase (NAG), albumin and amino acids in rats treated with either a single dose of sodium chromate (5 and 10 mg kg-1), repeated doses of gentamicin (5 and 20 mg kg-1), or cadmium (1 mg kg-1), and in aging rats (from 2 to 20 months). All treatments resulted in an early increased excretion of beta 2-m indicative of functional alterations of the proximal tubular cells. An increased NAG excretion was observed only at the highest dose of chromate and in the cadmium model but the relative increases of beta 2-m were much larger (up to 200 times the control values against four times the control values for NAG). From 2 to 20 months of age, urinary beta 2-m increases by a factor of four. Aminoacids excretion showed little sensitivity in the various models. Albumin showed little variations in purely tubular or in the tubular phase of renal injury but the chronic progressive nephrosis of aging rats caused a 40-fold increase in its excretion between 2 and 20 months of age. Therefore urinary beta 2-m, albumin and albumin/beta 2-m ratio provide useful tools in the assessment of nephrotoxicity and of its mechanisms in various experimental models.

Effect of β‐naphthoflavone and phenobarbital on the nephrotoxicity of chlorotrifluoroethylene and 1,1‐dichloro‐2,2‐difluoroethylene in the rat

“…The increases in γ GT and ALP enzymatic activity are indicative of a lesion in the brush-border region of the proximal tubules. The increases in urinary excretion of glucose and β 2 -m were a result of selective damage to the proximal tubule, which is the most important region for their reabsorption (Von Baeyer, 1981;Viau et al, 1986). In addition, the increases in the excretion of glucose, proteins and β 2 -m were similar to those reported for hexachlorobutadiene (Lock and Ishmael, 1979) and tetrafluoroethylene (Odum and Green, 1984).…”

Preclinical evaluation of novel urinary biomarkers of cadmium nephrotoxicity

“…Third, it is conserved across species (Vaidya et al, 2008), which could facilitate the extrapolation of the results of studies in animals to the results of studies on human populations and vice versa. With regard to the latter point, it is interesting to note that while NAG has been a useful early marker of Cd toxicity in humans (Jin et al, 1999; Moriguchi et al, 2003; Suwazono et al, 2006; Teeyakasem et al, 2007), our results as well as studies from other laboratories (Groten et al, 1994; Viau et al, 1986) indicate that it does not perform as well in rat models of Cd-induced kidney injury.…”

Evaluation of factors associated with cadmium exposure and kidney function in the general population

“…The kidney is the most sensitive target organ with regards to Cd toxicity. β 2 ‐MG and NAG in urine have been used as biomarkers to assess the effects of Cd on the kidney in occupational settings and Cd‐polluted areas as well as in animal studies (Viau et al, ; Kawada et al, ; Nordberg et al, ).…”