Avaliação dos efeitos do extrato aquoso das folhas de Citrus maxima (pomelo) em ratos Wistar submetidos à indução de esteatose hepática não alcoólica

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver changes, ranging from hepatic steatosis to hepatocellular carcinoma. Of varied etiology, that disease has the insulin resistance and the oxidative stress associated to its pathogenesis. Studies show that certain plants have biological activities capable of preventing and treating pathologies. Citrus maxima (Burm.) Merr. leaves have been shown to be beneficial to the organism and these activities are attributed to the presence of phytochemical compounds. Because of that, the objective of this study was to evaluate the phytochemical profile and in vitro antioxidant potential of the lyophilized aqueous extract of the C. maxima leaves, as well as the effects of this extract on Wistar rats submitted to hepatic steatosis induction by diet rich in lipids and fructose (FHD). Phytochemical analysis was performed by HPLC and evaluation of the in vitro antioxidant potential of the extract using the DPPH and ABTS methods. For the evaluation of in vivo effects, the animals were distributed in G1 (normal diet - ND), G2 (FHD), G3 (ND + extract 50mg/kg) and G4 (FHD + extract 50mg/kg). The experiment lasted 45 days and the weight was recorded weekly. On the 46th day, the animals' blood and liver were collected. The hematological, biochemical, oxidative stress and histological parameters were determined through traditional methodologies. In the phytochemical analysis the presence of phenolic compounds was observed, with caffeic acid and catechin being the major compounds. The extract showed a significant antioxidant potential in vitro, as it showed significant polyphenol content and was able to inhibit the radicals DPPH and ABTS. In the in vivo analysis, it was found that the diet used was able to induce the development of metabolic alterations that favored the formation of steatosis, since the G2 animals showed elevated hepatic enzymes activity, changes in serum and hepatic lipid profile and fat droplets formation in the hepatocytes. It was also observed changes in inflammatory markers, increased markers of oxidative damage and reduction of antioxidant defenses. The group that received the extract (G4) had a better lipid and hepatic profile compared to G2. Moreover, the extract did not provoke alterations in the weight gain of the animals and acted as anti-inflammatory, since G4 animals exhibited significantly reduced levels (p<0.05) of the inflammatory markers. In the liver, the extract significantly decreased (p<0.05) the content of fat, cholesterol and triglycerides compared to G2, as well as oxidative damage to lipids and protected the liver from steatosis. The extract also showed antioxidants activity, since G4 exhibited significantly reduced (p<0.05) levels of oxidative damage markers and improved antioxidant defense markers when compared to G2. Thus, the results suggest that the extract showed hepatoprotective activity against the accumulation of fat in the liver. Possibly, this protection capacity was a result of the combination of the hypolipidemic, anti-inflammatory and antioxidant activities revealed by the extract, and the presence of phenolic compounds is a probable cause for such activities. Therefore, the use of this extract may be a promising alternative to aid in the prevention of hepatic steatosis, as well as in the treatment of dyslipidemias.