Piceatannol Ameliorates Hepatic Oxidative Damage and Mitochondrial Dysfunction of Weaned Piglets Challenged with Diquat

Abstract

The liver is an organ that produces large amounts of reactive oxygen species (ROS). Human infants or piglets are prone to oxidative damage due to their uncompleted development of the antioxidant system, causing liver disease. Piceatannol (PIC) has been found to have significant antioxidant effects. The aim of this experiment was to investigate the effects of PIC on the liver in piglets experiencing oxidative stress caused by diquat (DQ). After weaning, 54 male piglets (Duroc × [Landrace × Yorkshire]) were selected and randomly divided into three treatment groups: the CON group, the DQ-CON group, and the DQ-PIC group. The two challenged groups were injected with DQ and then orally administrated either PIC or another vehicle solution, while the control group was given sterile saline injections and an orally administrated vehicle solution. Compared to the results of the CON group, DQ increased the percentage of apoptosis cells in the liver, also decreased the amount of reduced glutathione (GSH) and increased the concentration of malondialdehyde (MDA). In addition, the adenosine triphosphate (ATP) production, activities of mitochondrial complex I, II, III, and V, and the protein expression level of sirtuin 1 (SIRT1) were inhibited by DQ. Furthermore, PIC supplementation inhibited the apoptosis of hepatic cells caused by DQ. PIC also decreased MDA levels and increased the amount of GSH. Piglets given PIC supplementation exhibited increased activities of mitochondrial complex I, II, III, and V, the protein expression level of SIRT1, and the ATP production in the liver. In conclusion, PIC affected the liver of piglets by improving redox status, preserving mitochondrial function, and preventing excessive apoptosis.

Keywords: apoptosis; diquat; mitochondrial function; oxidative stress; piceatannol; piglet.

Figure 1

Representative images of hepatic tissue assessed by hematoxylin and eosin staining. CON, piglets were orally administrated vehicle solution (0.5% sodium carboxymethyl cellulose) and challenged with sterile saline; DQ-CON, piglets were orally administrated vehicle solution and challenged with diquat (10 mg/kg body weight); DQ-PIC, piglets were orally administrated piceatannol (80 mg/kg/day) and challenged with diquat (10 mg/kg body weight).

Figure 2

Effects of piceatannol supplementation on apoptosis of hepatic cells in diquat-induced piglets. TUNEL, terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling; CON, piglets were orally administrated vehicle solution (0.5% sodium carboxymethyl cellulose) and challenged with sterile saline; DQ-CON, piglets were orally administrated vehicle solution and challenged with diquat (10 mg/kg body weight); DQ-PIC, piglets were orally administrated piceatannol (80 mg/kg/day) and challenged with diquat (10 mg/kg body weight).

Figure 3

Effects of piceatannol supplementation on expression levels of protein related to apoptosis in the liver of diquat-induced piglets. The column and its bar represented the means value and SE (n = 6), respectively. Bcl-2, B-cell lymphoma-2; Bax, Bcl2-associated x; CON, piglets were orally administrated vehicle solution (0.5% sodium carboxymethyl cellulose) and challenged with sterile saline; DQ-CON, piglets were orally administrated vehicle solution and challenged with diquat (10 mg/kg body weight); DQ-PIC, piglets were orally administrated piceatannol (80 mg/kg/day) and challenged with diquat (10 mg/kg body weight). ^{a, b} Different letters on the shoulder mark indicate significant differences (p < 0.05).

Figure 4

Effects of piceatannol supplementation on the expression levels of protein related to antioxidant in the liver of diquat-induced piglets. The column and its bar represented the means value and SE (n = 6), respectively. Nrf2, nuclear-factor-erythroid-2-related factor 2; Keap1, kelch like ECH associated protein 1; SOD2, superoxide dismutase 2; CON, piglets were orally administrated vehicle solution (0.5% sodium carboxymethyl cellulose) and challenged with sterile saline; DQ-CON, piglets were orally administrated vehicle solution and challenged with diquat (10 mg/kg body weight); DQ-PIC, piglets were orally administrated piceatannol (80 mg/kg/day) and challenged with diquat (10 mg/kg body weight). ^{a, b, c} Different letters on the shoulder mark indicate significant differences (p < 0.05).

Figure 5

Effects of piceatannol supplementation on expression levels of SIRT1 protein in the liver of diquat-induced piglets. The column and its bar represented the means value and SE (n = 6), respectively. SIRT1, sirtuin 1; CON, piglets were orally administrated vehicle solution (0.5% sodium carboxymethyl cellulose) and challenged with sterile saline; DQ-CON, piglets were orally administrated vehicle solution and challenged with diquat (10 mg/kg body weight); DQ-PIC, piglets were orally administrated piceatannol (80 mg/kg/day) and challenged with diquat (10 mg/kg body weight). ^{a, b, c} Different letters on the shoulder mark indicate significant differences (p < 0.05).