Alpha-lipoic acid attenuates renal injury in rats with obstructive nephropathy

Abstract

This study was established to determine the possible protective effects of alpha-lipoic acid (ALA), a powerful antioxidant, on renal injury in obstructive nephropathy. Male Sprague-Dawley rats were assigned into sham-operated unilateral ureteral obstruction (UUO) and UUO treated with ALA groups. ALA 60 mg/kg was injected intraperitoneally 2 days before UUO induction and continued afterward for 7 days. Renal function, oxidative stress markers, nitric oxide, transforming growth factor-1 (TGF-β1), and histological changes were evaluated at the end of the experiment. Obstruction of the ureter resulted in renal dysfunction as indicated by significant increases in blood urea nitrogen and serum creatinine. Nonobstructed contralateral kidneys in all groups examined did not show any morphological or biochemical alterations. In untreated UUO group, the obstructed kidney developed marked hydronephrosis, leukocyte infiltration, and severe interstitial fibrosis. These functional and structural changes were associated with significant increases in tissue levels of malondialdehyde, nitric oxide, and TGF- β 1 but decreases in reduced glutathione and total antioxidant capacity. Pretreatment with ALA significantly minimized all the changes elicited by ureteral obstruction. These findings demonstrate that ALA supplementation attenuates renal injury in rats with obstructive nephropathy and further suggest that oxidative stress inhibition is likely to be involved in the beneficial effects of this compound.

Figure 1

The effects of unilateral ureteral obstruction (UUO) and alpha-lipoic acid (ALA) on (a) malondialdehyde (MDA), (b) reduced glutathione (GSH), and (c) total antioxidant activity (TAC). Values are mean ± SEM from 10 rats in each group. *P < 0.001 versus sham, ^† P < 0.01, ^†† P < 0.001 versus UUO within the same kidney. ^# P < 0.05, ^## P < 0.01, ^### P < 0.001 versus corresponding contralateral kidney.

Figure 2

Effects of unilateral ureteral obstruction (UUO) and alpha-lipoic acid (ALA) on (a) nitric oxide (NO) and (b) transforming growth factor-β1 (TGF-β1) levels. Values are mean ± SEM from 10 rats in each group. *P < 0.05, **P < 0.01, ***P < 0.001 versus sham, ^† P < 0.01, ^†† P < 0.001 versus UUO within the same kidney. ^# P < 0.01, ^## P < 0.001 versus corresponding contralateral kidney.

Figure 3

Effects of unilateral ureteral obstruction (UUO) and alpha-lipoic acid (ALA) on renal histopathological changes in the obstructed kidney from sham ((a), H&E 40x; (d), Masson's trichrome 40x) showing normal tubules and peritubular stromal tissues, UUO group ((b), H&E 40x; (e), Masson's trichrome 40x) showing dilated tubules, marked interstitial infiltration with polymorphonuclear leukocytes and severe interstitial fibrosis, UUO + ALA group ((c), H&E 40x; (f), Masson's trichrome 40x) showing mild leukocyte infiltration and less fibroblastic proliferation. The degree of leukocyte infiltration (g) and fibrotic area (h) are shown as mean ± SEM from 10 rats in each group. *P < 0.01, **P < 0.001 versus sham. ^† P < 0.001 versus UUO.