Prolonged Diuretic and Renoprotective Effects of a Xanthone Obtained from Garcinia achachairu Rusby in Normotensive and Hypertensive Rats

Abstract

The previous study showed that 1,5,8-trihydroxy-4',5'-dimethyl-2H-pyrano(2,3 : 3,2)-4-(3-methylbut-2-enyl) xanthone (TDP) obtained from Garcinia achachairu Rusby (Clusiaceae) branches induces acute diuresis in normotensive (NTR) and spontaneously hypertensive rats (SHR) after 8 h of the experiment. In complementarity, the present study evaluated the prolonged diuretic and renoprotective effects of TDP in both NTR and SHR. The animals received, once a day, oral treatment with TDP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (VEH; 10 mL/kg). At the end of 7 days, the urine, blood, and kidney samples were collected for biochemical and histological analyzes. The urinary volume of both NTR and SHR after 7 days of treatment with the TDP was significantly increased, associated with augmented urinary electrolyte excretion levels. The treatments did not modify the urinary pH values nor the parameters analyzed in plasma (Na⁺, K⁺, Cl^-, and Ca²⁺). Concerning the renal analyzes, when compared with the VEH-treated NTR group, while the activity of the enzymes catalase (CAT) and N-acetyl-β-D-glucosaminidase (NAG), as well as nitrite levels, were increased, the generation of lipid hydroperoxides and the activity of the enzyme myeloperoxidase (MPO) were unaltered. On the other hand, the activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) and the levels of reduced glutathione (GSH) in kidney homogenates of the SHR group were decreased. However, TDP augmented the levels of GSH and GST activities and reduced the levels of nitrite and the activities of CAT and MPO, when compared with VEH-treated only SHR. Besides, the treatment with TDP alleviated the morphological changes of the renal corpuscle region of SHR. Together, these results revealed the prolonged diuretic effect of TDP and their renal protective effect by improving the antioxidative capacity.

Figure 1

Molecular structure of the 1,5,8-trihydroxy-4′,5′-dimethyl-2H-pyrano(2,3 : 3,2)-4-(3-methylbut-2-enyl) xanthone (TDP).

Figure 2

Effect of TDP on renal markers of oxidative stress, endogenous antioxidants factors, and cell biomarkers after 7 days of treatment in rats. (a) Lipid hydroperoxides (LOOH) content, (b) reduced glutathione (GSH) levels, (c) superoxide dismutase (SOD) activity, (d) catalase (CAT) activity, (e) glutathione S-transferase (GST) activity, (f) myeloperoxidase (MPO) activity, (g) N-acetyl-β-D-glucosaminidase (NAG) activity, and (h) nitrite levels in kidney samples collected from normotensive rats (NTR) and spontaneously hypertensive rats (SHR). The results show the mean ± S.E.M. of 6–8 animals per group. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by Dunnett's multiple comparisons test. ^∗p < 0.05 when compared with the respective VEH group. #p < 0.05 when compared with the VEH-treated SHR group. TDP, 1,5,8-trihydroxy-4′,5′-dimethyl-2H-pyrano(2, 3 : 3, 2)-4-(3-methylbut-2-enyl) xanthone.

Figure 3

Representative images of renal tissue morphology stained by hematoxylin and eosin (H&E). (a) Normotensive rats and (b) spontaneously hypertensive rats. The blue and red arrows indicate Bowman's capsule region and the renal glomerulus, respectively. VEH,  vehicle (water plus 1% tween). HCTZ, hydrochlorothiazide, and TDP, 1,5,8-trihydroxy-4′,5′-dimethyl-2H-pyrano(2, 3 : 3, 2)-4-(3-methylbut-2-enyl) xanthone.