astaxanthine and Ureteral-Obstruction

Loss of peritubular capillaries is a notable feature of progressive renal interstitial fibrosis. Astaxanthin (ASX) is a natural carotenoid with various biological activities. The present study aimed to evaluate the effect of ASX on unilateral ureteral obstruction (UUO)‑induced renal fibrosis in mice. For that purpose, mice were randomly divided into five treatment groups: Sham, ASX 100 mg/kg, UUO, UUO + ASX 50 mg/kg and UUO + ASX 100 mg/kg. ASX was administered to the mice for 7 or 14 days following UUO. The results demonstrated that UUO‑induced histopathological changes in the kidney tissue were prevented by ASX. Renal function was improved by ASX treatment, as evidenced by decreased blood urea nitrogen and serum creatinine levels. Furthermore, the extent of renal fibrosis and collagen deposition induced by UUO was suppressed by ASX. The levels of collagen I, fibronectin and α‑smooth muscle actin were increased by UUO in mice or by transforming growth factor (TGF)‑β1 treatment in NRK‑52E cells, and were reduced by ASX administration. In addition, ASX inhibited the UUO‑induced decrease in peritubular capillary density by upregulating vascular endothelial growth factor and downregulating thrombospondin 1 levels. Inactivation of the TGF‑β1/Smad signaling pathway was involved in the anti‑fibrotic mechanism of ASX in UUO mice and TGF‑β1‑treated NRK‑52E cells. In conclusion, ASX attenuated renal interstitial fibrosis and peritubular capillary rarefaction via inactivation of the TGF‑β1/Smad signaling pathway.

Topics: Animals; Biomarkers; Biopsy; Cell Line; Disease Models, Animal; Fibrinolytic Agents; Fibrosis; Kidney Diseases; Male; Mice; Microvascular Rarefaction; Rats; Signal Transduction; Smad Proteins; Transforming Growth Factor beta1; Ureteral Obstruction; Vascular Endothelial Growth Factor A; Xanthophylls

To study the effects of astaxanthin on renal fibrosis and apoptosis induced by partial unilateral ureteral obstruction (UUO) in rats.. Ninety-six male adult SD rats were randomized into 6 equal groups, namely the blank control group, sham-operated group, UUO group, and astaxanthin group at high, medium, and low doses. Left ureteral ligation was performed in UUO and astaxanthin groups, and two days before the operation, the rats in astaxanthin groups were lavaged with 25, 50, or 100 mg/kg astaxanthin daily for 14 days, while the same volume of saline was given to rats in UUO group and sham-operated group. Renal pathological in the rats was observed with HE staining, and the expression levels of TGF-β1, SGK1, and CTGF in the left kidney were detected immunohistochemically; the expression level of Bcl-2 and Bax were detected using Bcl-2 and Bax detection kits.. Compared to UUO group, high- and medium-dose astaxanthin groups showed obviously ameliorated renal pathologies and reduced expressions of TGF-β1, SGK1, and CTGF in the left kidney with lessened renal cell apoptosis.. Astaxanthin can reduce UUO-induced renal fibrosis and renal cell apoptosis, demonstrating the renoprotective effect of astaxanthin against renal fibrosis.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Connective Tissue Growth Factor; Fibrosis; Immediate-Early Proteins; Kidney; Kidney Diseases; Male; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta1; Ureteral Obstruction; Xanthophylls