Protective effect of hesperidin on oxidative and histological liver damage following carbon tetrachloride administration in Wistar rats

Abstract

Introduction: In the current study, the protective effect of hesperidin (HP) on carbon tetrachloride (CCl4)-induced hepatotoxicity in rats was investigated.

Material and methods: Twenty-eight rats were divided equally into four groups. The first group was kept as a control and given only vehicle. In the second, rats were orally administered 50 mg/kg/day HP for 10 days. Carbon tetrachloride was given in a single intraperitoneal injection at the dose of 2 ml/kg in the third group. In the fourth group, the rats were treated with equal doses of CCl4 and HP.

Results: It was found that CCl4 induced oxidative stress via a significant increase in the formation of thiobarbituric acid-reactive substances (TBARS) and caused a significant decline in the levels of glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in rats. In contrast, HP blocked these toxic effects induced by CCl4, causing an increase in GSH, CAT and SOD levels and decreased formation of TBARS (p < 0.01). In addition, histopathological damage increased with CCl4 treatment. In contrast, HP treatment eliminated the effects of CCl4 and stimulated anti-apoptotic events, as characterized by reduced caspase-3 activation.

Conclusions: The current study demonstrated that CCl4-induced hepatotoxicity can be prevented with HP treatment. Thus, co-administration of HP with CCl4 may be useful for attenuating the negative effects of CCl4 on the liver.

Keywords: carbon tetrachloride; hepatotoxicity; hesperidin; liver.

Figure 1

In the liver, a normal histological appearance was observed following hematoxylin and eosin staining of the (A) control and (B) hesperidin (HP) groups VC – vena centralis; 20×.

Figure 2

In the CCl₄ group, we observed (A) distortion of the hepatocyte radial arrangement, hemorrhage and necrosis, (B) cell infiltration, (C) necrosis and hemorrhage, (D) vascular congestion and infiltration, (E) eosinophilic and pyknotic nuclei, and (F) vacuolization and congestion (A, B: H + E; 10×, C, D, E: H + E; 20×, F: H + E; 40×)

Figure 3

Histological findings were decreased in the CCl₄ + hesperidin (HP) group (A: H + E; 20×, B: H + E; 40×)

Figure 4

Immunohistochemical expression of caspase-3 in the (A) control, (B) hesperidin (HP), (C) CCl₄ and (D) CCl₄ + HP groups. The number of positively stained cells decreased in the CCl₄ + HP group. Positively stained caspase-3 cells are indicated by the arrows; 20×