Protective effects of D-005, a lipid extract from Acrocomia crispa fruits, against ischemia/reperfusion-induced acute kidney injury in rats

Abstract

Background: Acute kidney injury (AKI) induced by renal ischemia/reperfusion (IR) is associated with enhanced production of reactive oxygen species in renal tissues. D-005, a lipid extract obtained from Acrocomia crispa fruit, has previously shown antioxidant effects. The aim of this work was to evaluate the effects of D-005 on renal IR-induced AKI in rats.

Methods: Rats were randomized into seven groups including a negative control group (vehicle) without AKI and six groups with renal IR-induced AKI as follows: a positive control (vehicle); D-005 treatment at 25, 100, 200, or 400 mg/kg; and dexamethasone at 3 mg/kg. All treatments were orally administered as single doses 1 hour before AKI induction. Biomarkers (serum creatinine, urea, and uric acid concentrations), oxidative variables, and histopathological AKI changes were evaluated in blood and kidney tissues.

Results: All D-005 doses protected against IR-induced AKI in rats by significantly decreasing biomarkers and histopathological AKI changes as assessed by reduced serum concentrations of creatinine, urea, and uric acid. In addition, all D-005 doses decreased tubular damage, as shown by fewer detached cells and casts in the tubular lumen. D-005 reversed oxidation disturbance markers by decreasing malondialdehyde and sulfhydryl group concentrations in plasma and in kidney homogenates and by increasing kidney catalase activity. Dexamethasone, the reference substance, protected against IR-induced AKI in rats by reducing biochemical and histological variables of renal damage in a similar manner.

Conclusion: Administration of single oral doses of D-005 markedly and significantly protected against renal IR-induced AKI, possibly due to its known antioxidant effects.

Keywords: Acrocomia crispa; Acute kidney injury; D-005; Rats; Renal ischemia/reperfusion.

Figure 1

Effects of D-005 on serum creatinine concentrations in rats with IR-induced acute kidney injury. Data are presented as mean ± standard error. *P < 0.05, ***P < 0.001, compared to the positive control group (Mann–Whitney U test). DEX, dexamethasone; IR, renal ischemia/reperfusion.

Figure 2

Effects of D-005 on serum uric acid concentration in rats with IR-induced acute kidney injury. Data are presented as mean ± standard error. *P < 0.05, **P < 0.01, ***P < 0.001, compared to the positive control group (Mann–Whitney U test). DEX, dexamethasone; IR, renal ischemia/reperfusion.

Figure 3

Effects of D-005 on serum urea concentration in rats with IR-induced acute kidney injury. Data are presented as mean ± standard error. ***P < 0.001, compared to the positive control group (Mann–Whitney U test). DEX, dexamethasone; IR, renal ischemia/reperfusion.

Figure 4

Renal cortex of Sprague-Dawley rats. (A, B) Negative control, (C, D) positive control, (E, F) D-005 25 mg/kg, (G, H) D-005 100 mg/kg, (I, J) Dexamethasone 3 mg/kg. A, C, E, G, and I: periodic acid-schiff staining, 100 μm. B, D, F, H, and J: 50 μm. *, hyaline cast; NC, necrotic cells; PT, proximal tubules.

Figure 5

Effects of D-005 on tubular damage in rats with IR-induced acute kidney injury. Data are presented as mean ± standard error. *P < 0.05, **P < 0.01, compared to the positive control group (Student’s t test). DEX, dexamethasone; IR, renal ischemia/reperfusion.

Figure 6

Effects of D-005 on plasma concentration of malondialdehyde (MDA) in rats with IR-induced acute kidney injury. Data are presented as mean ± standard error. *P <0.05, **P < 0.01, ***P < 0.001, compared to the positive control group (Mann–Whit-ney U test). DEX, dexamethasone; IR, renal ischemia/reperfusion.

Figure 7

Effects of D-005 on plasma concentration of sulfhydryl (SH) groups. Data are presented as mean ± standard error. *P < 0.05, **P < 0.01, compared to the positive control group (Mann–Whitney U test). DEX, dexamethasone; IR, renal ischemia/reperfusion.

Figure 8

Effects of D-005 on malondialdehyde (MDA) concentration in rats with IR-induced acute kidney injury. Data are presented as mean ± standard error. *P < 0.05, **P < 0.01, ***P < 0.001, compared to the positive control group (Mann–Whitney U test). DEX, dexamethasone; IR, renal ischemia/reperfusion.

Figure 9

Effects of D-005 on sulfhydryl (SH) group concentration in rats with IR-induced acute kidney injury. Data are presented as mean ± standard error. *P < 0.05, **P < 0.01, compared to the positive control group (Mann–Whitney U test). DEX, dexamethasone; IR, ischemia/reperfusion.

Figure 10

Effects of D-005 on catalase (CAT) activity in rats with IR-induced acute kidney injury. Data are presented as mean ± standard error. *P < 0.05, ***P < 0.001, compared to the positive control group (Mann–Whitney U test). IR, ischemia/reperfusion.