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Purpose: Fenofibrate (FEN) is known as a nuclear receptor activator which regulates many pathophysiological processes, such as oxidative stress, inflammation, and leukocyte endothelium interactions. Recent studies have demonstrated an anti-oxidant, anti-inflammatory, and anti-ischemic role of FEN in the attenuation of ischemia-reperfusion (IR) injury in the kidney, liver, brain, and heart. The purpose of the present study was to examine the effect of FEN on intestinal recovery and enterocyte turnover after intestinal IR injury in rats.Methods: Male Sprague-Dawley rats were divided into four experimental groups: (1) sham rats underwent laparotomy, (2) sham-FEN rats underwent laparotomy and were treated with intraperitoneal (IP) FEN (20 mg/kg); (3) IR rats underwent occlusion of both the superior mesenteric artery and the portal vein for 30 min followed by 24 h of reperfusion, and (4) IR-FEN rats underwent IR and were treated with IP FEN immediately before abdominal closure. Intestinal structural changes, Park's injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 h following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real-time PCR, Western blot, and immunohistochemistry.Results: Treatment with FEN resulted in a significant decrease in Park's injury score in jejunum (32 %) and ileum (33 %) compared to IR animals. IR-FEN rats also demonstrated a significant increase in mucosal weight in jejunum (23 %) and ileum (22 %), mucosal DNA (38 %) and protein (65 %) in jejunum, villus height in jejunum (17 %) and ileum (21 %), and crypt depth in ileum (14 %) compared to IR animals. IR-FEN rats also experienced significant proliferation rates as well as lower apoptotic indices in jejunum and ileum which was accompanied with higher Bcl-2 levels compared to IR animals.Conclusions: Treatment with fenofibrate prevents intestinal mucosal damage and stimulates intestinal epithelial cell turnover following intestinal IR in a rat model. [ABSTRACT FROM AUTHOR]

Purpose: Taurine (TAU) is a sulfur-containing amino acid that is involved in a diverse array of biological and physiological functions, including bile salt conjugation, osmoregulation, membrane stabilization, calcium modulation, anti-oxidation, and immunomodulation. Several studies have established that treatment with TAU significantly protects cerebral, cardiac and testicular injury from ischemia-reperfusion (IR). The purpose of the present study was to examine the effect of TAU on intestinal recovery and enterocyte turnover after intestinal IR injury in rats.Methods: Male Sprague-Dawley rats were divided into four experimental groups: (1) Sham rats that underwent laparotomy, (2) Sham-TAU rats that underwent laparotomy and were treated with intraperitoneal (IP) TAU (250 mg/kg); (3) IR-rats that underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 48 h of reperfusion, and (4) IR-TAU rats that underwent IR and were treated with IP TAU (250 mg/kg) immediately before abdominal closure. Intestinal structural changes, Park's injury score, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. The expression of Bax, Bcl-2, p-ERK and caspase-3 in the intestinal mucosa was determined using Western blot and immunohistochemistry.Results: Treatment with TAU resulted in a significant decrease in Park's injury score compared to IR animals. IR-TAU rats also demonstrated a significant increase in mucosal weight in jejunum and ileum, villus height in jejunum and ileum and crypt depth in ileum compared to IR animals. IR-TAU rats also experienced significantly lower apoptotic indices in jejunum and ileum which was accompanied by a higher Bcl-2/Bax ratio compared to IR animals.Conclusions: Treatment with taurine prevents gut mucosal damage and inhibits intestinal epithelial cell apoptosis following intestinal IR in a rat. [ABSTRACT FROM AUTHOR]

Aim Of the Study: Notch signaling plays important roles in maintaining intestinal epithelial homeostasis. When Notch signaling is blocked, proliferation ceases and epithelial cells become secretory. The purpose of the present study was to evaluate the role of Notch signaling pathway following intestinal ischemia-reperfusion (IR) injury in a rat model.Materials and Methods: Male Sprague-Dawley rats were randomly divided into four experimental groups: Sham-24 and Sham-48 rats underwent laparotomy and were killed 24 or 48 h later, respectively; IR-24 and IR-48 rats underwent occlusion of SMA and portal vein for 30 min followed by 24 or 48 h of reperfusion, respectively. Enterocyte proliferation and enterocyte apoptosis were determined at killing. Notch-related gene and protein expression were determined using Real Time PCR, Western blotting and immunohistochemistry 48 h followed IR.Main Results: IR-48 rats demonstrated significantly increased rates of cell proliferation and increased cell apoptosis in both jejunum and ileum compared to Sham rats. IR-48 rats exhibited a significant decrease in Notch-1 protein expression (Western blot) that was coincided with a significant decrease in the number of Notch-1 positive cells (immunohistochemistry) in jejunum (35% decrease, p < 0.05) and ileum (twofold decrease, p < 0.05) as well as Hes-1 positive cells in jejunum (28% decrease, p < 0.05) and ileum (31% decrease, p < 0.05) compared to Sham-48 rats.Conclusions: Forty-eight hours following intestinal IR in rats, accelerated cell turnover was associated by inhibited Notch signaling pathway. Intestinal stem cells differentiation toward secretory progenitors rather than differentiation toward absorptive cells is important at this phase of intestinal recovery. [ABSTRACT FROM AUTHOR]

Background: Exposure to ionizing radiation results in cytotoxic and genotoxic effects caused mainly by the oxidative damage. In the present study, we investigated the radioprotective effect of novel antioxidant cocktail on germ cell apoptosis and spermatogenesis in rats subjected to whole body radiation (WBIR).Methods: Adult male rats weighing 250-270 g were divided into four groups, eight rats each. Group 1 served as untreated control, group 2 received an IP single dose of antioxidant cocktail (1 ml). Group 3 was exposed to a WBIR (6 Gy). Group 4 received antioxidant cocktail before WBIR. Rats from each group were killed after 48 h. MDA levels were measured in serum (TBARS assay). Johnsen's criteria and the number of germinal cell layers were used to categorize spermatogenesis. TUNEL assay was used to determine germ cell apoptosis. Statistical analysis was performed using one-way ANOVA test.Results: WBIR resulted in histological testicular damage (decrease in Johnsen's criteria, p < 0.05) that was accompanied by a significant increase in germ cell apoptosis, expressed as the number of apoptotic cells per 100 tubules (AI-1 apoptotic index) and the number of positive tubules per 100 tubules (AI-2 apoptotic index). Treatment with antioxidant cocktail resulted in a significant decrease in germ cell apoptosis (33% decrease in AI-1, p < 0.05 and 34% decrease in AI-2, p < 0.05) that was accompanied by an improved spermatogenesis (increase in Johnsen's criteria, p < 0.05).Conclusions: In a rat model of WBIR, antioxidant treatment ameliorates oxidative stress-induced testicular damage, decreases germ cell apoptosis and improves spermatogenesis. [ABSTRACT FROM AUTHOR]