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. 2016 May 6;24(1):15.
doi: 10.1186/s40199-016-0154-9.

Effects of phloretin on oxidative and inflammatory reaction in rat model of cecal ligation and puncture induced sepsis

Mehdi Aliomrani  1   2 , Mohammad Reza Sepand  1   2 , Hamid Reza Mirzaei  3 , Ali Reza Kazemi  1   2 , Saeid Nekonam  4 , Omid Sabzevari  5   6
Affiliations

Effects of phloretin on oxidative and inflammatory reaction in rat model of cecal ligation and puncture induced sepsis

Mehdi Aliomrani et al. Daru. .

Abstract

Background: Sepsis is a debilitating systemic disease and described as a severe and irregular systemic inflammatory reaction syndrome (SIRS) against infection. We employed CLP (Cecal Ligation and Puncture) model in rats to investigate anti-inflammatory and antioxidant effects of phloretin, as a natural antioxidant agent, and its protective effect on liver tissue damage caused by sepsis.

Methods: Male Wistar albino rats were randomly divided into three groups: sham group, CLP induced sepsis group and phloretin treated CLP group. Sepsis was induced by CLP method. 50 mmol/kg Phloretin was administered intraperitoneally in two equal doses immediately after surgery.

Results: It was observed that blood urea nitrogen (BUN) and tumor necrosis factor alpha (TNF-α) levels were dramatically increased in the CLP induced sepsis group (43.88 ± 1.905 mg/dl, 37.63 ± 1.92, respectively) when compared to the sham group. Moreover, tissue Glutathione (GSH) and liver nuclear factor ĸB (NF-ĸB p65) transcription factor values were higher in CLP induced sepsis group. This elevation was considerably reduced in the phloretin treated CLP group. No significant differences were observed in serum creatinine and creatinine phosphokinase levels.

Conclusions: The present study suggested that phloretin, as a natural protective agent, act against tissue damages introduced following the experimental sepsis induced model, likely caused by free oxygen radicals.

Keywords: Antioxidants; NF-ĸB; Oxidative stress; Phloretin; Sepsis; TNF- α.

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Figures

Fig. 1
Fig. 1
a Serum level of BUN in Sham (negative control), CLP (cecal ligation and puncture as a positive control) and CLP + P (CLP rats treated with Phloretin) in 24 h after sepsis induction by CLP. Data are presented as mean ± SEM. CLP (cecal ligation and puncture) vs. Sham group (****) p < 0.0001, CLP+ phloretin vs. CLP group (##) p < 0.01. b and c. Serum level of Creatinine and creatinine phosphokinase, respectively (n = 7 per group). Data are presented as mean ± SEM. CLP (cecal ligation and puncture) vs. Sham group (*) p < 0.05
Fig. 2
Fig. 2
Changes in serum tumor necrosis factor-alpha (TNF-α) in CLP (cecal ligation and puncture) and phloretin treated rats. Results are expressed as mean ± SEM for 7 rats. CLP (cecal ligation and puncture) vs. Sham group (***) p < 0.001, CLP+ phloretin vs. CLP group (##) p < 0.01
Fig. 3
Fig. 3
ELISA results of NF-ĸB in liver extract. Bars represent the Sham group NF-ĸB transcription factor as 100 %. CLP (cecal ligation and puncture) vs. sham group (****) p < 0.0001, CLP+ phloretin vs. CLP group (##) p < 0.01
Fig. 4
Fig. 4
Liver tissue sections are shown. a: in the sham group, central vein, normal sinusoids and hepatocytes with regular morphology are seen. b: through sepsis group, enormous vascular obstruction, extreme cytoplasmic vacuoles (→), sinusoidal duct dilation, damaged hepatocytes and stimulated Kupffer cells are observed. c: in the sepsis group treated with phloretin, mildly damaged hepatocytes (→), moderate vascular obstruction and sinusoidal duct dilatation are noted. Hepatic parenchyma slides were stained with hematoxylin-eosin, original magnification: X400
See this image and copyright information in PMC

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