Protective Effect of N-Acetylcysteine on Progression of Adriamycin-induced Nephropathy

Effects of antioxidants on the established nephropathy were investigated. The experimental nephropathy was induced in rats by intravenous injection of adriamycin (2 mg/kg). Six weeks later, when proteinuria was apparent, the rats were supplemented with N-acetylcysteine (NAC, 1 g/kg/day) in drinking water for additional 6 weeks. Glomerulosclerosis score and tubulointerstitial injury index were determined by light microscopy. Expression of transforming growth factor (TGF) beta1 and laminin beta1 was determined in the renal cortex by reverse transcription-polymerase chain reaction, Western blotting, immunohistochemistry, and immunogold electron microscopy. The adriamycin-induced proteinuria as well as the glomerulosclerosis and tubulointerstitial injury was ameliorated by the treatment with NAC. Adriamycin increased the expression of TGF beta1 mRNA and protein, which was ameliorated by NAC. Although the expression of laminin beta1 mRNA was increased, adriamycin did not significantly alter that of its protein. These results indicate that antioxidants ameliorate the established nephropathy in association with normalization of overexpressed TGF beta1.

Effects of Renin-angiotensin System Blockade on Tubulointerstitial Lesions in Adriamycin-induced Nephropathy / 대한신장학회잡지

PURPOSE: Effects of renin-angiotensin system blockade on tubulointerstitial lesions were examined in adriamycin-induced nephropathy. METHODS: Male Sprague-Dawley rats were used. The three experimental groups were intravenously injected with adriamycin (2 mg/kg). After 6 weeks, rats showing heavy proteinuria were orally treated with either cilazapril 1 mg/kg/day (ACEi group, n=7) or losartan 10 mg/kg/day (ARB group, n=7) during the period of additional 6 weeks. The other group was maintained without any drugs (ADR group, n=6). The control group was without adriamycin treatment and maintained during the 12 weeks (Control, n=5). RESULTS: Systolic blood pressure was increased following the adriamycin treatment, which was normalized by treatment with cilazapril or losartan. Accordingly, cilazapril and losartan normalized the 24-h urine protein/creatinine ratio, in association with morphologic improvement of tubulointerstitial lesions. The expression of laminin beta1 was not altered in any experimental groups. CONCLUSION: These results suggest that angiotensin II plays an important role in tubulointerstitial lesions in adriamycin-induced nephropathy.

Localization of Laminin and Laminin beta 1 chain on Gomeruli of Developmental Rat Kidney / 체질인류학회지

Laminin, an extracellular matrix glycoprotein composed of three polypeptide chains such as alpha , beta, and gamma is distributed in basement membranes of epithelium, muscle, and nervous tissues. Laminin functions as an extracellular cytoskeleton and regulates the differentiation and polarization of cells adjacent to the basement membrane. Along with type IV collagen and heparan sulfate proteoglycan, laminin forms a spike -like structure in the renal glomerular basement membrane (GBM). It has been previously demonstrated that the distribution and immune reaction of laminin are changed in response to the conditions of glomerulonephritis and that laminin plays a role in the reformation of GBM as well as the regeneration of renal glomerular cells. In the present study, the profile of expression and distribution of laminin/laminin beta1 chain were examined in different developmental stages and upon adriamycin administration. Kidney obtained from fetuses (16, 18, and 20 days old) and infants (1 and 7 days old) of Sprague -Dawley rats were either cryosectioned for immunohistochemical assays or ultrathin -sectioned for electron microscopy using immunogold staining methods. The results were as follows: 1. Intensive expression of laminin was observed in the GBM and surrounding mesenchymal tissues obtained from 16, 18, and 20 days old fetuses and in the glomerulus from one day neonates, whereas the level of staining decreased in the glomerulus from 7 days old infants. 2. Immunogold particles were observed in the comma -shaped nephron, in particular in cisternae of rough endoplasmic reticulum, vesicles and nuclear membrane of endothelial cells and mesangial cells obtained from 18 days old fetuses. 3. The immune reactions of laminin beta1 chain were trace detected in the kidney from fetuses (16, 18, and 20 days old) and weakly in tissues surrounding blood capillary and mesangial tissues from one day old neonates. 4. After 24 hours following adriamycin treatment, the reactivity of laminin was slightly enhanced in the renal glomerulus, when compared with that of untreated controls. This enhancement persisted up to 1 week of adriamycin treatment. Laminin beta1 chain was weakly detectable, while further treatment with adriamycin for another 24 hours reduced the intensity of laminin beta1 chain. Taken together, these results suggest that laminin is localized in the GBM at the high level during early fetal stages but the expression levels decrease after birth. Moreover, administration with adriamycin may result in an increase in the immune reactivities of laminin and laminin beta1 chain by renal tissue damage followed by renal regeneration.