Exposure to hydrocarbons and renal disease: an experimental animal model.
The association between hydrocarbon exposure and chronic glomerulonephritis is still a controversial scientific issue. Recent epidemiological evidence suggests a role of exposure to hydrocarbons in the progression of glomerulonephritis towards chronic renal failure. The present experimental study on rats has been designed to assess the possible role of styrene in the progression of adriamycin (ADR) nephrosis, a well known model of renal fibrosis following nephrotic syndrome induced by ADR. Female Sprague-Dawley rats were exposed to styrene, 300 ppm, 6 h/day, 5 days/week for 12 weeks (group 1); treated with ADR, 2 mg/Kg, i.v., twice on day 1 and day 15 of the study (group 2); Additional groups of animals received both the styrene and ADR treatments (group 3) or served as controls (group 4). The urinary excretion of total and single proteins (albumin, Retinol-Binding Protein (RBP), Clara Cell 16 Kd protein (CC16), fibronectin) was measured monthly, whereas histopathology and determinations requiring blood sampling were carried out at the end of the experiment. A progressive increase in total proteinuria, falling in the nephrotic range already by the 6th week was observed in ADR-treated groups. Styrene exposure caused up to a 3- to 5-fold increase as compared to controls. Co-exposure to ADR and styrene also resulted in a proteinuria much greater than that caused by ADR alone. The interactive effect of styrene and ADR was statistically significant for albuminuria and urinary fibronectin. A similar response was observed for glomerular filtration rate at the end of the experiment, styrene-exposed animals showing hyperfiltration as compared to their respective control group. At the end of the experiment, histopathological scoring for interstitial infiltration and fibrosis was also significantly higher in styrene-treated animals as compared to their respective control groups. In ADR-treated rats, low molecular weight proteinuria (l.m.w.p.) was only slightly affected, suggesting minimal tubular dysfunction associated with extensive tubular atrophy. However, styrene-exposed animals showed l.m.w.p. higher than their respective controls. In summary, in this animal model we were able to confirm both styrene-induced microproteinuria, mainly albuminuria and minor increases in l.m.w.p., observed among occupationally exposed workers and the role of hydrocarbon exposure as a factor accelerating the progression of renal disease suggested by epidemiological investigations in patients suffering from chronic renal disease. Whereas in rats exposed to styrene only, microproteinuria was stable over time and minor histopathological changes were noted at the end of the experiment, evidence of a role of solvent exposure in the progression of ADR nephropathy was obtained in terms of both renal dysfunction and interstitial fibrosis. The mechanistic basis of styrene-ADR interaction is unclear. However, experimental evidence is consistent with epidemiological findings suggesting the need to avoid solvent exposure in patients suffering from renal diseases.
Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma Medical School, Italy. scot@ipruniv.cce.unipr.it
A
A
Mutti
T
T
Coccini
R
R
Alinovi
G
G
Toubeau
F
F
Broeckaert
E
E
Bergamaschi
P
P
Mozzoni
D
D
Nonclercq
A
A
Bernard
L
L
Manzo
D000419:Albuminuria / Q000139:chemically induced / Q000652:urine; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D005353:Fibronectins / Q000652:urine; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000652:urine; D006838:Hydrocarbons / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D011507:Proteinuria / Q000139:chemically induced / Q000652:urine; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000633:toxicity*; D020058:Styrene / Q000633:toxicity*
D000970:Antineoplastic Agents; D005353:Fibronectins; D006838:Hydrocarbons; D012997:Solvents; D020058:Styrene; D004317:Doxorubicin