Erratum: Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension.

[This corrects the article DOI: 10.3892/etm.2016.3808.].

Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension.

The aim of the present study was to increase the intestinal transport of octreotide (OCT) by targeting the first-pass impact to identify a potential method for decreasing portal vein pressure (PVP) using oral OCT. Thus, the bioavailability of intestinally absorbed OCT was evaluated in normal rats and rats with portal hypertension (PH) that had been administered P-glycoprotein/multidrug resistance-associated protein 2/cytochrome P450 3A4 (P-gp/MRP2/CYP3A4) inhibitors. The mRNA and protein expression levels of P-gp, MRP2 and CYP3A4 were evaluated in normal and PH rats with or without OCT and the inhibitors using RT-PCR, western blot and immunohistochemical analyses. The potential effects of the inhibitor administration on PVP were also examined. The results suggest that P-gp, MRP2 and CYP3A4 play important roles in prohibiting the enteral absorption of OCT, particularly under a PH environment. Moreover, inhibitors of P-gp, MRP2 and CYP3A4 decrease the first-pass effects of OCT and effectively reduce PVP under PH conditions. Therefore, the present results suggest P-gp, MRP2 and CYP3A4 are key factors in the intestinal absorption of OCT. The inhibition of P-gp, MRP2 and CYP3A4 can markedly decrease the first-pass effects of OCT, and their use may facilitate the use of orally administered OCT.

pH-sensitive microemulsion-based gels for removal of colonic ammonia: a novel preventative oral preparation for hepatic encephalopathy in rats.

Microemulsions with limited stability in mimetic gastrointestinal environments have previously demonstrated potential for the effective removal of ammonia from artificial colonic fluid. Specialized pH­sensitive microemulsion­based gels for the removal of colonic ammonia (MBG­RCA), however, possess relative stability in the gastrointestinal (GI) tract of normal rats, indicating potential use in in vivo applications. An investigation of the effects of oral MBG­RCA was conducted in order to evaluate the reduction of intestinal ammonia and the prevention of hepatic encephalopathy (HE) in rat models. Eighty rats were allocated into eight 4­day treatment groups: The HE model (intraperitoneal injection of thioacetamide) group; the high­, medium­ and low­dose MBG­RCA therapeutic groups (15, 10 and 5 ml/kg MBG­RCA, respectively); and the normal, blank, lactulose and acetic acid control groups, each of which received daily treatment administration. Oral MBG­RCA effects were identified using behavioral monitoring observed by an infrared night vision supervisory control system, electroencephalograms, blood ammonia levels, intestinal ammonia levels, liver functionality and pathological observation. High­ and medium­dose oral administrations of MBG­RCA significantly decreased the blood and intestinal ammonia levels (P<0.05), improved liver functionality and reduced the clinical manifestations of HE in rats. MBG­RCA demonstrated high clearance of rat colonic ammonia while maintaining sufficient stability in the GI tract, indicating the potential for the development of new clinically relevant oral preparations for the prevention of HE. Additionally, such preparations are advantageous in that ammonia is eliminated without the production of potentially harmful metabolic byproducts.

Sinomenine sensitizes multidrug-resistant colon cancer cells (Caco-2) to doxorubicin by downregulation of MDR-1 expression.

Chemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that sinomenine can enhance the absorption of various P-gp substrates. In the present study, we investigated the effect of sinomenine on the chemoresistance in colon cancer cells and explored the underlying mechanism. We developed multidrug-resistant Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1 genes as well as activation of the NF-κB signal pathway in MDR-Caco-2 cells. Importantly, we found that sinomenine enhances the sensitivity of MDR-Caco-2 cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through inhibition of the NF-κB signaling pathway. These findings provide a new potential strategy for the reversal of P-gp-mediated anticancer drug resistance.

A study on the position and etiology of infection in cirrhotic patients: A potential precipitating factor contributing to hepatic encephalopathy.

Hepatic encephalopathy (HE) is a severe and high-mortality complication in cirrhotic patients. In this study, we analyzed infection, one of the common precipitating factors of HE in patients with cirrhosis, in order to identify common infection sites and the etiology. In addition, we aimed to identify information useful in the early prevention and effective treatment of HE. Ninety-two patients presenting with hepatitis B virus-related cirrhosis with HE (HBC-HE) and 45 patients presenting with alcoholic cirrhosis with HE (ALD-HE) were enrolled in this study. We collected and analyzed data concerning the precipitating factors of HE using blood tests, biochemical detection and bacterial culture to identify which precipitating factor was the most common. Fifty-three patients with HE (37 with HBC-HE and 16 with HBC-HE) had infection as the precipitating factor. These infections included respiratory tract infection (56.6%), intestinal tract infection (20.7%), peritoneal infection (17.0%) and urinary tract infection (5.7%). The white blood cell (WBC) counts increased in 17 cases (32.1%) and neutrophil (NEUT) numbers increased in 39 cases (73.6%), while WBC counts were lower in the patients with respiratory tract infection compared with those in the patients with infections at other sites (P<0.05). The levels of plasma ammonia were significantly higher in patients with intestinal tract infection than in those with other sites of infection (P<0.05). The proportions of patients with hyperammonemia, increased NEUT numbers, hyponatremia and low albumin were higher in the infection group compared with those in the non-infection group (P<0.05). Pneumococci and E. coli were common bacteria that induced infection in the respiratory tract and at other infection sites, respectively. Respiratory tract infection was identified to be the most common precipitating factor for HE.