Enhanced prostaglandin biosynthesis in chronic partial ureteral obstruction is suppressed by atorvastatin
Authors: Ma Hongbao , Imam Syed , Yang Yan , Chou Shyan‐Yih 
Published: November 2023

Progressive loss of renal function in obstructive uropathy is invariably associated with tubulointerstitial inflammation and fibrosis. We have created a rat model of chronic partial ureteral obstruction (PUO) to study means of attenuating renal fibrosis. Atorvastatin is a statin widely used in clinical practice as an HMG‐CoA reductase inhibitor. Besides lipid‐lowering effects, statins may exert pleiotropic actions such as constraining inflammatory processes. In rats with chronic PUO, we have previously reported that administration of atorvastatin decreases tubulointerstitial fibrosis and improves renal function (J Urol. 182:1860‐8, 2009). In view of augmented prostaglandin synthesis in obstructive uropathy, we examined in the present study the effects of atorvastatin on renal biosynthesis of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2, a stable metabolite of TXA2) in rats with PUO. Four groups of rats, consisting of 8 rats in each group, were studied. All rats underwent removal of the right kidney. To create PUO, the left ureter was incorporated into the psoas muscle, which was split and reapproximated. The rats received a regular diet or the same diet but supplemented with atorvastatin (50 mg/kg body weight atorvastatin per day) and were studied 30 days after the surgery. Four groups of rats were studied. Group 1 rats served as the control, underwent a sham surgery, and were fed on a regular diet. In Group 2, rats were subjected to PUO and placed on a regular diet. In Group 3, sham‐operated rats were fed on a regular diet containing atorvastatin. In Group 4, PUO rats were on a diet supplemented with atorvastatin. After the kidneys were harvested, the cortical and medullary tissues were separately homogenized, centrifuged and the extracts measured for PGE2 and TXB2 by ELISA. In Group 2, the tissue level of PGE2 was 4.2±0.5 in the cortex and 802.4±95.3 ng/g protein in the medulla, significantly higher than those in Group 1 (1.1±0.3 in the cortex and 348.8±70.1 in the medulla, respectively). In Group 2, TXB2 was 2.4±0.2 in the cortex, and 75.2±9.2 in the medulla, significantly greater than those in Group 1 (1.4±0.2 and 5.7±0.6 ng/g protein, respectively). Treatment with atorvastatin in PUO rats (Group 4) resulted in a significant reduction in the tissue levels of both PGE2 and TXB2, while no significant changes occurred in the sham‐operated rats (Group 3). In Group 4, the tissue level of PGE2 was 2.1±0.3 in the cortex and 522.2±62.1 ng/g protein in the medulla, significantly lower than those in Group 2. In Group 4, the TXB2 level was 1.9±0.3 in the cortex, and 51.3±6.2 in the medulla, significantly lower than those in Group 2. These results demonstrate that PUO enhances renal biosynthesis of PGE2 and TXB2, suggesting involvement of prostaglandins in the inflammatory process in chronic obstructive uropathy. This process is ameliorated by the use of a statin such as atorvastatin, thereby renal fibrosis is reduced.

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