The effects of TRPM2, TRPM6, TRPM7 and TRPM8 gene expression in hepatic ischemia reperfusion injury.

OBJECTIVE: Mammalian transient receptor potential melastatin (TRPM) channels are a form of calcium channels and they transport calcium and magnesium ions. TRPM has eight subclasses including TRPM1-8. TRPM2, TRPM6, TRPM7, TRPM8 are expressed especially in the liver cell. Therefore, we aim to investigate the effects of TRPM2, TRPM6, TRPM7, and TRPM8 gene expression and histopathologic changes after treatment of verapamil in the hepatic ischemia-reperfusion rat model. MATERIALS AND METHODS: Animals were randomly assigned to one or the other of the following groups including sham (n=8) group, verapamil (calcium entry blocker) (n=8) group, I/R group (n=8) and I/R- verapamil (n=8) group. TRPM 2, 6, 7, 8 gene expression level was were assessed by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and histopathologic changes were determined by the hematoxylin and eosin (HE) examination. RESULTS: The expression level of TRPM 2, 6, 7, and 8 genes was were significantly higher in ischemia-reperfusion (I/R), verapamil, IR-verapamil groups compared to sham group. The p-values were 0.0024, < 0.0001, 0.0002, 0.006 for TRPM2, TRPM6, TRPM7, and TRPM8, respectively. Severe necrotic, degenerative differentiations and severe hemorrhagic areas were observed in hepatocytes from IR group. Also, moderate necrotic and degenerative differentiations and moderate hemorrhagic areas were observed in hepatocytes from IR-verapamil group. CONCLUSIONS: This is the first study reporting an association between the expression level of TRPM 2, 6, 7, 8 in a hepatic ischemia-reperfusion rat model. Moreover, TRPM 2, 6, 7, 8 affect hepatic ischemia-reperfusion.

The effect of peritoneal dialysis with alkaline dialysate in peritonitis carcinomatosis: an experimental study in mice.

OBJECTIVE: The aim of this study was to neutralize acidic pH using an alkaline dialysate for continuous ambulatory peritoneal dialysis (CAPD) in mice with peritoneal carcinomatosis (PC) and to investigate the change of the pH level in the acidic fluid along with its effects on liver oxidative stress, liver and kidney histopathology and the lifespan of the body. MATERIALS AND METHODS: A total of 38 mice were randomly divided into 4 groups.PC development was inhibited by intraperitoneal injection of Ehrlich tumor cells in all mice in each group. RESULTS: In the group-1 receiving CAPD, the pH levels of acidic liquid were higher; and the levels of liver TBARS were lower with higher reduced glutathione levels. Histopathological damage in group-1 was less than in group-2. In Group 3 receiving CAPD, the average lifespan extended by 10.4%. The average lifespan extended by 26.1%. CONCLUSION: This study indicated that applying CAPD with alkaline dialysate in PC contributed to the neutralization of acidosis of the intraperitoneal acid structure;had favorable effects on oxidative stress markers in liver tissue; prevented histopathological injury in liver and kidney tissues, and extended the life span of the body in mice. As this is a simple, inexpensive, and easily available method, larger studies are warranted to evaluate its effects.

Effect of sildenafil on intestinal adaptation parameters in a rat model of short bowel syndrome.

OBJECTIVE: We aimed to evaluate the effect of sildenafil on the intestinal adaptation in short bowel syndrome (SBS). MATERIALS AND METHODS: Forty-eight male Wistar-albino rats (weight, 231-390 g) were randomly divided into four groups with 12 rats in each. Group TA had only ileal transection+anastomosis, Group TA+S was given sildenafil after ileal transection+anastomosis, Group RA had a resection of 75% of the small bowel+anastomosis, Group RA+S was given sildenafil after small bowel resection+anastomosis. Sildenafil was injected subcutaneously at 60 mg/kg/day dose throughout 3-21 days postoperatively. Bowel and mucosal weights, villus height, crypt depth, DNA and protein concentrations were determined. RESULTS: Jejunal bowel weight was lower in TA and TA+S groups than RA and RA+S groups (p < 0.05). RA+S group had higher ileal and jejunal mucosal weights than RA and TA+S groups (p < 0.05). Villus height was highest in RA+S group both in ileum and jejunum (466.1 ± 38.6 µm and 648.1 ± 65.7 µm, respectively). Jejunal crypt depth was highest in RA+S group (255.1 ± 21.9 µm) compared to other groups (p < 0.05). There was no significant difference in ileal and jejunal protein concentration between TA and TA+S groups and in ileal protein concentration between RA ve RA+S groups (p > 0.05). Ileal DNA concentration was higher in TA+S group, and jejunal DNA concentration was higher in RA and RA+S groups than TA and TA+S groups (p < 0.05). CONCLUSIONS: Sildenafil has a positive effect on intestinal adaptation parameters, particularly in jejunum in a rat SBS model. Thus, its role in the treatment of SBS should be further investigated with clinical studies.