The Aqueous Extract from the Stem Bark of Garcinia lucida Vesque (Clusiaceae) Exhibits Cardioprotective and Nephroprotective Effects in Adenine-Induced Chronic Kidney Disease in Rats

Abstract

Chronic kidney disease (CKD) is a serious health problem with high morbidity and mortality, mainly attributable to cardiovascular risk. Garcinia lucida is traditionally used in Cameroon for the management of cardiovascular diseases. The aim of this study was to evaluate the cardioprotective and nephroprotective effects of the aqueous extract from the stem bark of G. lucida (AEGL). The in vitro antioxidant effect of AEGL was assessed at concentrations ranging 1-300 μg/mL against DPPH, lipid peroxidation, and AAPH-induced hemolysis. The reducing power and phenolic and flavonoids contents were also determined. CKD was induced by intraperitoneal bolus injection of adenine (50 mg/kg/day) for 4 consecutive weeks to male Wistar rats. AEGL (150 and 300 mg/kg/day) or captopril (20 mg/kg/day) was concomitantly administered with adenine per os. Bodyweight and blood pressure were monitored at baseline and weekly during the test. At the end of the experiment, plasma creatinine, urea, AST, and ALT were quantified. Proteinuria, creatinine excretion, and creatinine clearance were also assessed. The effect on GSH, CAT, and SOD activity was evaluated in cardiac and renal homogenates. Sections of the heart and kidney were stained with hematoxylin and eosin. AEGL exhibited a potent in vitro antioxidant activity and was shown to possess a large amount of phenolic compounds. Adenine alone increased blood pressure, cardiac and kidney mass, proteinuria, protein to creatinine ratio, plasma creatinine, AST, and urea levels (p < 0.05, 0.01, and 0.001). Besides, the bodyweight and creatinine clearance were significantly reduced (p < 0.05 and p < 0.01). All these alterations were blunted by the plant extract, except the bodyweight loss. In addition, AEGL improved GSH levels and CAT and SOD activities. AEGL attenuated adenine-induced glomerular necrosis, tubular dilatation, and cardiac inflammation. AEGL exhibits cardioprotective and nephroprotective effects that may be ascribed to its antihypertensive and antioxidant activities.

Figure 1

DPPH radical scavenging activity (a), total reducing power (b), antilipid peroxidation (c), and antihemolytic effects of the aqueous extract of Garcinia lucida.

Figure 2

Effect of the aqueous extract of Garcinia lucida on systolic (a) and diastolic (b) blood pressure on adenine-induced chronic kidney disease. All values are expressed as mean ± SEM from 6 rats. ^∗p < 0.05^,∗∗p < 0.01, and ^∗∗∗p < 0.001 compared to the control and ^μp < 0.05, ^μμp < 0.01, and ^μμμp < 0.001 compared to adenine. AEGL, aqueous extract of Garcinia lucida.

Figure 3

Effect of the aqueous extract of Garcinia lucida on heart rate in adenine-induced chronic kidney disease. All values are expressed as mean ± SEM from 6 rats. ^μp < 0.05 compared to adenine. AEGL, aqueous extract of Garcinia lucida.

Figure 4

Effect of the aqueous extract of Garcinia lucida or captopril on rat plasma ALT (a) and AST (b) contents. All values are expressed as mean ± SEM from 6 rats. ^∗p < 0.05,^∗∗p < 0.01, and^∗∗∗p < 0.001 compared to the control and ^μp < 0.05, ^μμp < 0.01, and ^μμμp < 0.001 compared to adenine. AEGL, aqueous extract of Garcinia lucida.

Figure 5

Effect of the aqueous extract of Garcinia lucida on renal markers in adenine-induced chronic kidney disease. All values are expressed as mean ± SEM from 6 rats. ^∗p < 0.05, ^∗∗p < 0.01, and^∗∗∗p < 0.001 compared to the control and ^μp < 0.05, ^μμp < 0.01, and ^μμμp < 0.001 compared to adenine. AEGL, aqueous extract of Garcinia lucida.

Figure 6

Representative photomicrographs showing the effect of the aqueous extract of Garcinia lucida (AEGL) on renal and cardiac histology in adenine-treated rats. The normal structure of the rat kidney is observed in the control group. Kidney from the adenine-treated group presented a general disorganization of the architecture, glomerular necrosis (blue arrow), and diffuse tubular dilatation (yellow arrow). The kidney from adenine + captopril-treated rat showed tiny glomerular degeneration and moderate tubular dilatation. In animals that received adenine + AEGL (150 mg/kg) or + AEGL (300 mg/kg), inflammatory cell infiltration (black arrow) and slight tubular dilatation were observed. Heart photomicrographs showed normal structure in the control group. Important inflammatory cell infiltration accompanied with increased intercellular spaces (green arrows) in adenine-treated animals. Scanty increase in intercellular space was observed in the adenine + captopril group. Extract-treated groups showed only increased intercellular spaces that was substantially reduced with AEGL at 300 mg/kg. Sections were stained with H&E. The kidney was observed at 400x, while the heart was pictured at 100x.