High Dose Pomegranate Extract Suppresses Neutrophil Myeloperoxidase and Induces Oxidative Stress in a Rat Model of Sepsis.

Introduction: The effect of using high dose pomegranate extract on sepsis and its safety is not clarified. Considering the fact that proper immune and inflammatory responses are needed to cope with infection, the aim of current study was to assess the effect of high dose pomegranate extract consumption on oxidative and inflammatory responses after disease induction in rat model of sepsis. METHODS: Sepsis was induced by Cecal Ligation and Perforation (CLP) surgery. Adult male Wistar rats were divided into three groups of eight animals: Sham; CLP and POMx [consumed POMx (250 mg of pomegranate fruit extract/kg/day) for four weeks before CLP]. RESULTS: Peritoneal neutrophil myeloperoxidase activity was significantly lower in POMx compared with Sham and CLP groups (p < 0.01 and p < 0.05, respectively). Although antioxidant enzymes were higher in POMx group after sepsis induction, lower serum total antioxidant status (TAS) (p < 0.01 compared with both CLP and Sham groups) and higher liver thiobarbituric acid reactive species (TBARS) levels were observed in this group (p < 0.01 and p < 0.05, compared with Sham and CLP groups, respectively). CONCLUSION: High dose POMx consumption prior to sepsis induction, suppressed the vital function of neutrophils in early hours after sepsis initiation, resulting in higher oxidative stress. These findings indicate that caution should be made in using high dose pomegranate products. The main message of current study is that such useful compounds as antioxidants including pomegranate juice which have beneficial effects on general health status may have detrimental effects if misused or used in high doses.

The effect of pomegranate extract on survival and peritoneal bacterial load in cecal ligation and perforation model of sepsis in rats.

BACKGROUND: Sepsis is one of the major causes of death in intensive care units. Oxidative stress and hyper-inflammation has been shown to be major cause of mortality and morbidity in septic cases. Pomegranate is a fruit considered for its antioxidant and anti-inflammatory properties. The aim of this study is to evaluate the effect of a standard pomegranate fruit liquid extract (POMx), on mortality and peritoneal bacterial load in cecal ligation and perforation (CLP) sepsis model. METHODS: Male wistar rats were divided into four groups of 24 each: sham; CLP; prevention (consumed POMx [250 mg of polyphenols/kg/day] for 4 weeks before CLP); treatment (received a single drink of POMx [250 mg of polyphenols/kg] after CLP). Each group was divided into three subgroups, each containing eight animals, for bacterial load and survival (with and without antibiotics) studies. Sepsis was induced by CLP surgery. Ten day survival rate was recorded. Peritoneal bacterial load was also assessed. Data were analyzed using Log-rank and Kruskal-Wallis tests. RESULTS: There was no significant difference in survival rate of CLP, prevention and treatment groups, in subgroups without antibiotics. However, in subgroups with antibiotics, the prevention group had significantly lower survival rate than sham group (P < 0.05). Conversely, the bacterial load of prevention and treatment groups were significantly higher than sham group (P < 0.01). CONCLUSIONS: Our study demonstrates for the first time that pomegranate extract could increase mortality rate via increasing peritoneal cavity bacterial load, in CLP sepsis model. More studies to assess mechanisms of this effect are warranted.

The modifying effects of fish oil on fasting ghrelin mRNA expression in weaned rats.

Ghrelin expression and secretion seem to be influenced by the fat content of the diet. However, data on the probable adverse effect of high fat diet (HFD) with different dietary fats and saturation level of fatty acids is inconclusive. This study aimed at investigating the effects of HFDs on fasting total and acyl-ghrelin plasma levels, gastric fundus and duodenum ghrelin mRNA expressions. Weaned Wistar rats (n=50) were randomly divided to five groups of HFDs with fish oil (HF-F), olive oil (HF-O), soy oil (HF-S), butter (HF-B) and the controls. After 8 weeks, blood samples were collected. While the animals were fasting for 24h, their blood and tissue samples were obtained. Plasma parameters of total and acyl ghrelin and ghrelin mRNA expression level in stomach and duodenum were measured. The HF-B fed group had lower fasting plasma acyl ghrelin level than the control, HF-F and HF-O groups (P<0.05); furthermore, the HF-F group had significantly higher acyl ghrelin level than the HF-S one (P<0.05). After feeding, all the groups, except for the HF-B one, had a significantly lower plasma acyl ghrelin levels (P<0.05), compared with the fasting state. Ghrelin mRNA expression levels in the gastric fundus and duodenum were significantly lower in the HF-B as compared to the control group. Furthermore, the HF-F group had significantly higher mRNA level in the duodenum, in comparison with the HF-B and HF-S groups. As HF-F and HF-O diets had the highest stimulatory effect on fasting ghrelin expression and plasma level, consumption of these dietary oils can play an important role in ghrelin regulation, which might affect feeding behavior and energy intake.

Fish oil and olive oil can modify insulin resistance and plasma desacyl-ghrelin in rats.

BACKGROUND: Evidence exists for reciprocal effects of insulin and desacyl-ghrelin (DAG) concentration, but the association between different fatty acid saturation in high fat diet (HFD) and these hormones remain to be established. To evaluate the impact of different sources of dietary fat and the level of fatty acid saturation on plasma insulin and DAG levels and also the association of DAG with insulin action this study was carried out. METHODS: Male weaning Wistar rats were randomly divided into four groups of HFDs, high fat butter (HF-B), high fat soy (HF-S), high fat olive (HF-O), high fat fish (HF-F), and a group of standard diet (SD). Blood samples were collected after 8 weeks and after they were fasted for 24 h. Body weight, food intake, plasma glucose, insulin, DAG and insulin resistance (HOMA-IR) were measured. RESULTS: Plasma insulin levels at fed and fasted status, were significantly higher in rats on HF-B compared to those on SD, HF-F and HF-O diets (P<0.05). Insulin concentration in rats on HF-S was also higher than those on SD, HF-F and HF-O diets (P<0.05), in the feeding status. Insulin resistance was significantly higher in rats on HF-B, compared to those on SD, HF-F and HF-O (P<0.05). Rats that were fed with HF-B diet had lower fasting plasma DAG levels than the SD, HF-F and HF-O groups (P<0.05); furthermore, the HF-F group had significantly higher DAG level than the HF-S groups (P<0.05). CONCLUSIONS: Fish and olive oils may hence contribute to lower insulin level and HOMA-IR by increasing DAG concentration and may have more health benefits than other fat sources in diets.