Streptomycin alleviates irinotecan-induced delayed-onset diarrhea in rats by a mechanism other than inhibition of β-glucuronidase activity in intestinal lumen.

Irinotecan hydrochloride (CPT-11) is a useful drug for cancer chemotherapy but sometimes induces severe diarrhea clinically. CPT-11 is mainly activated to SN-38 by carboxylesterase (CES) and then detoxified to SN-38 glucuronide (SN-38G) by UDP-glucuronosyltransferase (UGT) in the liver. SN-38G is excreted via bile and de-conjugated to SN-38 by β-glucuronidase (β-GLU) in the intestinal content.

Relationship between the in vitro response of dendritic cells to Lactobacillus and prevention of tumorigenesis in the mouse.

Background: Some strains of lactobacilli stimulate immune cells, yet little is known about their potency in cancer prevention. We have previously reported that Lactobacillus casei Shirota (LcS) suppresses murine tumorigenesis through immune modulation. In this study, differences were compared among six representative strains of lactobacilli in regard to their ability to stimulate bone marrow cell-derived dendritic cells (BMDCs) in vitro and tumor suppression in vivo.

Involvement of UDP-glucuronosyltransferase activity in irinotecan-induced delayed-onset diarrhea in rats.

We assessed the involvement of UDP-glucuronosyltransferase (UGT) activity in episodes of irinotecan hydrochloride (CPT-11)-induced delayed-onset diarrhea using a mutant rat strain with an inherited deficiency of UGT1A (Gunn rats). Gunn rats exhibited severe diarrhea after the intravenous administration of CPT-11 at a dose of 20 mg/kg, whereas Wistar rats did not. In the epithelium of the small intestine and cecum in Gunn rats, the shortening of villi, degeneration of crypts, and destruction of the nucleus were observed.

Intestinal microflora: probiotics and autoimmunity.

Lactobacillus casei strain Shirota (LcS) has been demonstrated to have beneficial effects in numerous murine disease models via host immune modulation. It has also been reported that LcS induced recovery of host immune responses that were decreased by treatment with carcinogens and augmented the natural killer activity and T-cell functions of host immune cells. After LcS is ingested by the host, it is incorporated into M cells in Peyer's patches (PP) and digested to form active components.

Probiotic Lactobacillus casei activates innate immunity via NF-kappaB and p38 MAP kinase signaling pathways.

Probiotic bacteria are microorganisms that benefit the host through improvement of the balance of intestinal microflora and possibly by augmentation of host defense systems. We examined the mechanisms for the up-regulation of innate immune responses by a probiotic Lactobacillus casei ATCC27139, in vivo. Using mouse models of systemic Listeria monocytogenes infection and MethA fibrosarcoma tumorigenesis in combination with BALB/c and SCID mice, we found that parenteral administration of L.

Antitumor activity and action mechanisms of Lactobacillus casei through the regulation of immune responses.

Lactobacillus casei strain Shirota (LcS) has been demonstrated to have beneficial effects in numerous disease models, especially murine autoimmune disease and carcinogenesis models, via host immune modulation. It has also been reported that LcS induced recovery of the host immune responses that were decreased by treatment with carcinogens, and that augmented the natural killer activity and T cell functions of host immune cells. After LcS is ingested by the host, it is incorporated into M cells in Peyer's patches (PP) and digested to form active components.

Cloning of Mongolian gerbil cDNAs encoding inflammatory proteins, and their expression in glandular stomach during H. pylori infection.

Mongolian gerbils are considered to be a good animal model for understanding the development of Helicobacter pylori-associated diseases. However, limitations regarding the genetic information available for this animal species hamper the elucidation of underlying mechanisms. Thus, we have focused on identifying the nucleotide sequences of cDNAs encoding Mongolian gerbil inflammatory proteins, such as interleukin-1 (IL-1beta), tumor necrosis factor alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS).

Suppression of Helicobacter pylori-induced gastritis by green tea extract in Mongolian gerbils.

Since urease of Helicobacter pylori is essential for its colonization, we focused attention on foodstuffs which inhibit the activity of this enzyme. Among plant-derived 77 foodstuff samples tested, some tea and rosemary extracts were found to clearly inhibit H. pylori urease in vitro.

Inhibitory effects of N-(3,5-dimethoxy-4-n-octyloxycinnamoyl)-N'-(3,4-dimethylphenyl)piperazine (YIC-C8-434), an acyl-CoA:cholesterol O-acyltransferase inhibitor, on cholesterol esterification in the intestine and liver.

The effects of an acyl-CoA:cholesterol O-acyltransferase (ACAT) inhibitor, N-(3,5-dimethoxy-4-n-octyloxycinnamoyl)-N'-(3,4-dimethylphenyl)piperazine (YIC-C8-434), on cholesterol esterification in the intestine and liver were investigated in vitro and in vivo. YIC-C8-434 inhibited the formation of cholesteryl [(3)H]oleate from [(3)H]oleic acid and cholesterol both in human colon adenocarcinoma Caco2 cells and in human hepatoma HepG2 cells with IC(50) values of 0.38 and 0.

Alleviation of side effects induced by irinotecan hydrochloride (CPT-11) in rats by intravenous infusion.

Purpose: Irinotecan hydrochloride (CPT-11) is a potent topoisomerase I inhibitor and is established and used widely as an antitumor agent. However, it sometimes causes severe side effects such as myelosuppression and diarrhea. These dose-limiting toxicities prevent the adoption of CPT-11 in aggressive chemotherapy.

The metabolic stability of acyl-CoA: cholesterol O-acyltransferase (ACAT) inhibitors, N-(4-benzyloxy-3, 5-dimethoxycinnamoyl)-N'-(2, 4-dimethylphenyl)piperazine (YIC-708-424) and its derivatives in rat liver and intestinal epithelium.

The metabolic stability of the acyl-CoA: cholesterol O-acyltransferase (ACAT) inhibitor N-(4-benzyloxy-3, 5-dimethoxycinnamoyl)-N'-(2, 4-dimethylphenyl)piperazine (YIC-708-424) and its n-alkoxy derivatives containing an alkyl chain of 3 or 7 to 10 carbons, which exhibited different hypocholesterolemic activities, was investigated in vivo and in vitro in rats. After the oral administration of YIC-708-424 to rats at a dose of 5 mg/kg/d for 7 d, the parent compound was not detected in the blood. On the other hand, when the n-alkoxy derivatives were administered to rats, an increase in the alkyl chain length produced a progressive increase in the blood concentration of the parent compound.

Lipoteichoic acids from Lactobacillus strains elicit strong tumor necrosis factor alpha-inducing activities in macrophages through Toll-like receptor 2.

Lactobacilli are nonpathogenic gram-positive inhabitants of microflora. At least some Lactobacillus strains have been postulated to have health beneficial effects, such as the stimulation of the immune system. Here we examined the stimulatory effects of lactobacilli on mouse immune cells.

Preventive effects of Cladosiphon fucoidan against Helicobacter pylori infection in Mongolian gerbils.

Background: Recently, the acquisition by Helicobacter pylori of resistance to antibiotics has become a serious problem. Therefore, nonantibiotic substances are required to diminish H. pylori-induced gastric lesions.

Assessment of safety of lactobacillus strains based on resistance to host innate defense mechanisms.

Seven Lactobacillus strains belonging to four species were evaluated for pathogenicity as well as for in vitro sensitivity to the bactericidal mechanisms of macrophages in a rabbit infective endocarditis (IE) model. Two bacteremia-associated strains, L. rhamnosus PHLS A103/70 and L.