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Exp Ther Med
2016 Jul 01;121:222-230. doi: 10.3892/etm.2016.3321.
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Antiseptic effect of sea cucumber (Holothuria atra) against multi-organ failure induced by sepsis: Molecular and histopathological study.
Saad DY
,
Baiomy AA
,
Mansour AA
.
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Sepsis is a systemic inflammatory response to infection and severe sepsis patients can develop acute lung and liver injury. The aim of the present study was to evaluate the efficacy of Holothuria atra methanolic body wall extract (HaE), as an antioxidant and anti-inflammatory agent against induced sepsis in a cecal ligation and puncture (CLP) rat model. In total, 30 males albino rats were divided into three groups (n=10 each) as follows: Sham (Sh), which was used as negative control; sepsis (Se), which was used as a positive control and was subjected to CLP surgery; and Ho, which was subjected to CLP and fed with 200 mg/kg (body weight) of HaE, once daily for 7 days. Subsequently, the expression of various genes was detected by polymerase chain reaction, while liver and lung tissues were examined by immunohistochemistry. The expression of Caspase-3 was significantly reduced in liver and lung tissues in the Ho group, while the expression levels of Gsta2, Cat and Sod1 genes were slightly reduced in the Ho group, when compared with the Se group. In addition, expression levels of tumor necrosis factor, interferon-γ, liver interleukin (IL)1b and lung IL1a were reduced in the Ho group compared with the Se group. Furthermore, histopathological changes were observed in liver tissues of the Se group, including congestion of hepatoportal blood vessel and focal hepatic necrosis, while lung tissues showed marked edema, hemorrhage and alveolar septal thickening. The Ho group showed apparent normal hepatic parenchyma and slight interstitial pneumonia. Immunohistochemical staining of caspase-3 in liver and lung tissues showed no expression in the Sh group, strong expression in the Se group and moderate expression in the Ho group. In conclusion, HaE demonstrated beneficial effect against induced sepsis, which may be attributed to its antioxidant and antiapoptotic activities.
Figure 1. Mortality rate of rats in the sham, sepsis group (cecum ligation and puncture) and septic group treated with Holothuria atra extract (Ho group).
Figure 2. Expression of the responsive genes (A) Caspase-3, (B) Gsta2, (C) Cat, (D) Sod1, (E) TNF and (F) IFN-γ in the liver and lung tissues, as well as of (G) Il1b in the liver and Il1a in the lung tissues, in Sh, Se and Ho rat groups. Data represent the mean ± standard error. *P<0.05 vs. Sh group; #P<0.05 vs. Se group. Sh, sham (negative control) group; Se, CLP-induced sepsis group; Ho, sepsis and Holothuria atra extract-treated group; CLP, cecal ligation and puncture; Gsta2, glutathione S-transferase α2; Cat, catalase; Sod1, superoxide dismutase 1; TNF, tumor necrosis factor; IFN, interferon; Il, interleukin.
Figure 4. Photomicrograph of rat lung. (A) Sham group, showing the normal histological structure of alveoli (a), alveolar sac (s) and thin alveolar septum (arrow); bar, 14.52 µm. (B) Septic group, showing interstitial pneumonia characterized by edema (o), hemorrhage (h) and leukocyte infiltration (f); bar, 14.21 µm. (C) Sepsis and Holothuria atra extract treatment group, revealing slight interstitial pneumonia (arrow); bar, 15.15 µm. All stained with hematoxylin-eosin.
Figure 5. Photomicrograph of immunohistochemical staining of Caspase-3 in rat liver and lungs. Liver tissues: (A) Sham (Sh) group, showing no expression of Caspase-3; bar=14.84 µm. (B) Septic (Se) group, showing strong expression of Caspase-3 (arrows); bar=13.58 µm. (C) Sepsis and Holothuria atra extract treatment (Ho) group, showing mild expression of Caspase-3 (arrows); bar=13.57 µm. Lung tissues: (D) Sh group, showing no expression of Caspase-3; bar=14.83 µm. (E) Se group, showing strong expression of Caspase-3 (arrows); bar=15.16 µm. (F) Ho group, showing mild expression of Caspase-3 (arrows); bar=14.82 µm. cv, central vein; h, hepatocyte; a, alveoli.
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