ABSTRACT
Background/Aims@#Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. @*Methods@#Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. @*Results@#LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. @*Conclusions@#LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.
ABSTRACT
Objective: To observe the expression of angiotensin II ( Ang II) and its receptors in a rat model of chronic cyclosporine (CsA) nephrotoxicity. Methods: Chronic CsA nephrotoxicity was induced in Sprague-Dawley rats by administering CsA (15 mg/kg s. c.) for 4 weeks. The body weight, systolic blood pressure, serum CsA, serum creatinine (Cr), and creatinine clearance rate (Ccr) of rats were examined in each group. Trichrome staining was used to observe the tubulointerstitial fibrosis; expressions of Ang II and its receptors (AT1 and AT2) were examined by immunohistochemical staining and Western blotting analysis. Results: Compared with the control rats, CsA-treated rats showed decreased body weight, increased Cr, decreased Ccr and tubulointerstitial fibrosis (P < 0.01). Immunohistochemistry revealed that the immunoreactivity of Ang II was significantly increased in the CsA-treated rats (47±7 vs 13±4, P < 0.01), with the immunoreactivity mainly locating to the juxtaglomerular afferent arterioles, and the immunoreactivity was significantly correlated with tubulointerstitial fibrosis (r=0. 769, P<0.001). Western blotting analysis showed significantly decreased AT1 expression ([114±14]% vs [42±6]%, P<0.01) and increased AT2 expression ([129±23]% vs [469±43]%, P<0.01). Conclusion: The findings of our study suggest that the intrarenal renin-angiotensin system is activated during chronic CsA nephrotoxicity, which is manifested by increased Ang II immunoreactivity, and this increased immunoreactivity is closely related to tubulointerstitial fibrosis.