Chronic kidney disease (CKD) has become a worldwide health and social problem. Retarding its progression to end-stage renal disease is beneficial both to the patients and the healthcare system. Plenty of clinical trials have indicated that enema with Chinese medicine could effectively prevent chronic renal failure, and was widely used in the clinical practice. However, studies on mechanism were still nearly blank, which may prevent further improvement of therapeutic efficacy. Recent studies had discovered that colon was an important organ where uremic toxins were generated. The uremic toxins involved could not only promote CKD progression, but also was closely correlated with CKD mortality. Reducing production and promoting excretion of toxins were confirmed to reduce renal tubule interstitial fibrosis and delay renal progression. On the basis of the theory of gut-kidney axis above, we had conducted pilot clinical researches to evaluate the effect of enema with Chinese medicine on the intestinal flora, gut barrier, enterogenous uremic toxins and renal protection. The preliminary results revealed that rheum enema through colon could accelerate intestinal dynamics, improve intestinal barrier function, regulate intestinal flora and reduce production and absorption of intestine-derived uremic toxins such as indoxyl sulfate, which may reduce renal fibrosis and delay renal progression. Further studies could provide more evidence for colon as a new therapeutic target for the treatment of CKD with Chinese medicine.
Colon ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Enema ; Humans ; Kidney ; drug effects ; pathology ; Renal Insufficiency, Chronic ; drug therapy ; pathology ; Treatment Outcome

OBJECTIVETo study the pathogenic and tumorigenic effect of 1,2-dimethylhydrazine (DMH) on the colon and ovaries of mice.

METHODSSixty ICR female mice were randomly divided into groups A and B for intraperitoneal injection of DMH (20 mg/kg) and saline (control) once a week for 24 weeks, respectively. The mice were sacrificed at 12, 16, 20, 24, 28 and 32 weeks after the first DMH injection for pathological examination of the colon and ovaries.

RESULTSIn group A, colorectal adenomas were found in 7, colorectal adenocarcinomas in 5, and hemorrhagic lesions of the ovaries with chronic inflammatory in 21 mice. Choriocarcinoma in the ovaries were detected in one mouse at 28 weeks and in another at 32 weeks. No obvious pathological changes were found in group B following the injections.

CONCLUSIONIntraperitoneal injection of DMH may induce colon tumors and ovarian diseases in mice.

1,2-Dimethylhydrazine ; toxicity ; Animals ; Colon ; drug effects ; pathology ; Colonic Neoplasms ; chemically induced ; Female ; Mice ; Mice, Inbred ICR ; Ovarian Diseases ; chemically induced ; Ovary ; drug effects ; pathology

Colonic necrosis is known as a rare complication following the administration of Kayexalate (sodium polystryrene sulfonate) in sorbitol. We report a rare case of colonic mucosal necrosis following Kalimate (calcium polystryrene sulfonate), an analogue of Kayexalate without sorbitol in a 34-yr-old man. He had a history of hypertension and uremia. During the management of intracranial hemorrhage, hyperkalemia developed. Kalimate was administered orally and as an enema suspended in 20% dextrose water to treat hyperkalemia. Two days after administration of Kalimate enema, he had profuse hematochezia, and a sigmoidoscopy showed diffuse colonic mucosal necrosis in the rectum and sigmoid colon. Microscopic examination of random colonic biopsies by two consecutive sigmoidoscopies revealed angulated crystals with a characteristic crystalline mosaic pattern on the ulcerated mucosa, which were consistent with Kayexalate crystals. Hematochezia subsided with conservative treatment after a discontinuance of Kalimate administration.
Adult ; Colon/*pathology ; Gastrointestinal Hemorrhage/etiology ; Humans ; Hyperkalemia/drug therapy ; Intestinal Mucosa/*pathology ; Male ; Necrosis/*chemically induced/complications/pathology ; Polystyrenes/*adverse effects/therapeutic use ; Uremia/*physiopathology

OBJECTIVETo evaluate the safety and efficacy of composite sophora colon-soluble capsule (CSCC) in treating ulcerative colitis (UC) of the damp-heat accumulation syndrome pattern (DHAS) and to prepare a basis for a phase III clinical trial.

METHODSA multi-center, randomized, single-blind, and positive drug parallel-controlled design was adopted. There were 126 patients of UC-DHAS stratified and assigned equally to three groups. Patients in two CSCC treated groups, Groups T1 and T2, were treated orally with high (six capsules, thrice a day) and low (four capsules, thrice a day) doses CSCC, and patients in the control group were treated orally with Mesalazine Enteric-coated Tablets (four tablets, thrice a day), respectively, all for eight weeks. The clinical efficacy and safety of treatments were evaluated through clinical symptom observations and colonoscopic examinations.

RESULTS(1) Full analysis set (FAS) and per-protocol set (PPS) analyses showed the comprehensive curative effect in Groups T1, T2, and the control group, obtaining the values of 85.7%, 92.9%, and 71.4% (P=0.330), and 89.5%, 92.7%, and 73.2% (P=0.552), respectively, demonstrating no statistical significance among the three groups. (2) FAS and PPS analysis showed the efficacy on membranous lesions in Groups T1, T2, and the control group, obtaining the values of 83.3%, 92.9%, and 73.8% (P=0.063), and 86.8%, 92.7%, and 75.6% (P=0.070), respectively, showing statistical insignificance among the three groups. (3) FAS analysis showed an efficacy tendency on improving tenesmus (P=0.056). No changes were found in improving the other symptoms, and statistical significance was not shown among the three groups (P>0.05). PPS analysis showed the efficacy on single item symptom in Groups T1, T2, and the control group was not statistically significant among the three groups (P=0.082).

CONCLUSIONSThe comprehensive effect of CSCC in treating UC is basically equivalent to that of Mesalazine enteric-coated tablet; however, the tendency was shown to improve symptoms. Its efficacy could not be raised by increasing the dosage used. Therefore, the recommended dosage of CSCC is four capsules, three times a day.

Adult ; Capsules ; Colitis, Ulcerative ; drug therapy ; Colon ; drug effects ; pathology ; Female ; Humans ; Intestinal Mucosa ; drug effects ; pathology ; Male ; Medicine, Chinese Traditional ; Plant Extracts ; adverse effects ; pharmacology ; therapeutic use ; Single-Blind Method ; Sophora ; chemistry ; Treatment Outcome

OBJECTIVETo observe the effect of Bawei Xilei powder on CD3, CD4, CD8 T-lymphocytes in peripheral blood and colonic mucosa of rat with ulcerative colitis.

METHODSixty SD rats were randomly divided into 6 groups, normal group, model group, low, middle and high dosage Bawei Xilei powder group, Sulfasalazine group. Ulcerative colitis was induced by immunization with rabbit 's colonic mucous emulsified with completely Freund's adjuvant in all rats. Rats in low, middle and high dosage Bawei Xilei powder group were administered with 0.05, 0.1, 0.2 mg Bawei Xilei powder for 18 days by enema respectively. While rats in Sulfasalazine group were enema administered with 100 mg Sulfasalazine, and the rats in other group were administered with equal volume of saline enema as control. We analyzed expression of CD3, CD4, CD8 T-lymphocytes in peripheral blood by flow cytometry and in colonic mucous by immunohistochemistry.

RESULTIn peripheral blood, compared with normal group, in model group, the increased of CD4 T-lymphocytes and CD4 /CD8 ratio, the reduced of CD8 T-lymphocytes, these results were significant discrepancy (P < 0.01). Compared with model group, after treatment with Bawei Xilei powder, CD8 T-lymphocytes increased, but only high dosage Bawei Xilei powder group had discrepancy (P < 0.05). But low dosage Bawei Xilei powder group, other treatment groups' rats showed CD4/CD8 ratio were reduced significantly (P < 0.05). In colonic mucous, compared with normal group, in model group, Rats showed that expression of CD3, CD4 T-lymphocytes reduced and CD8 T-lymphocytes increased obviously (P < 0.05, P < 0.01). Compared with model group, expression of CD8 T-lymphocytes reduced significantly in all treatment groups (P < 0.05, P < 0.01).

CONCLUSIONBawei Xilei powder may regulate their balance between T-lymphocytes subgroup, consequently relieve inflammatory injury in favor of ulcer reparation and tissue regeneration.

Animals ; CD3 Complex ; metabolism ; CD4 Antigens ; metabolism ; CD8 Antigens ; metabolism ; Colitis, Ulcerative ; immunology ; metabolism ; Colon ; drug effects ; metabolism ; pathology ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation ; drug effects ; Powders ; Rats ; T-Lymphocytes ; drug effects ; metabolism

OBJECTIVETo analyze the immunological characteristics of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model and examine the therapeutic effects and mechanisms of Astragalus polysaccharides (APS) treatment.

METHODSThirty-two male specific pathogen free Spragne-Dawley rats were randomly equally assigned to four groups: control, TNBS, APS and prednisone groups. Experimental colitis was induced by enema administration of TNBS. Then rats were treated with APS (0.5 g•kg•day, once daily) or prednisone (1.0 mg•kg•day, once daily) by gavage for 14 days. Macroscopic lesion and histological damage were determined, and activity of myeloperoxidase (MPO) was measured in the colonic tissues. Expressions of T-box expressed in T-cells (T-bet) and GATA-binding protein-3 (GATA-3) were determined by immunohistochemistry analysis and western blot.

RESULTSBoth macroscopic lesion and histological colonic damage induced by TNBS were reduced by APS and prednisone treatment. These were accompanied by significant attenuation of MPO activity (P=0.03). TNBS intervention enhanced the expression of both GATA-3 and T-bet, but the expression of T-bet was significantly enhanced than that of GATA-3, resulting in significant reduction of GATA-3/T-bet ratio (P=0.025). APS administration enhanced the expression of T-bet (P=0.04) and GATA-3 (P=0.019) in comparison to TNBS group, and resulting in an up-regulated GATA-3/T-bet ratio. Prednisone treatment inhibited both expressions; however it also resulted in up-regulation of the GATA-3/T-bet ratio.

CONCLUSIONSThese results demonstrated that APS exerted a beneficial immune regulatory effect on experimental colitis. It promoted the expression of T helper cell 1 (Th1) and T helper cell 2 (Th2) specific transcription factors but ultimately favor a shift toward Th2 phenotype, suggesting that APS possessed therapeutic potential in experimental colitis.

Animals ; Astragalus Plant ; chemistry ; Blotting, Western ; Colitis ; drug therapy ; pathology ; Colon ; drug effects ; pathology ; GATA3 Transcription Factor ; metabolism ; Immunohistochemistry ; Immunomodulation ; drug effects ; Male ; Peroxidase ; metabolism ; Polysaccharides ; pharmacology ; therapeutic use ; Rats, Sprague-Dawley ; T-Box Domain Proteins ; metabolism ; Trinitrobenzenesulfonic Acid

Nitric oxide (NO) is a non-adrenergic, non-cholinergic neurotransmitter found in the enteric nervous system that plays a role in a variety of enteropathies, including inflammatory bowel disease. Alteration of nitrergic neurons has been reported to be dependent on the manner by which inflammation is caused. However, this observed alteration has not been reported with acetic acid-induced colitis. Therefore, the purpose of the current study was to investigate changes in nitrergic neuromuscular transmission in experimental colitis in a rat model. Distal colitis was induced by intracolonic administration of 4% acetic acid in the rat. Animals were sacrificed at 4 h and 48 h postacetic acid treatment. Myeloperoxidase activity was significantly increased in the acetic acid-treated groups. However, the response to 60 mM KCl was not significantly different in the three groups studied. The amplitude of phasic contractions was increased by Nomega-nitro-L-arginine methyl ester (L-NAME) in the normal control group, but not in the acetic acid-treated groups. Spontaneous contractions disappeared during electrical field stimulation (EFS) in normal group. However, for the colitis groups, these contractions initially disappeared, and then reappeared during EFS. Moreover, the observed disappearance was diminished by L-NAME; this suggests that these responses were NO-mediated. In addition, the number of NADPH-diaphorase positive nerve cell bodies, in the myenteric plexus, was not altered in the distal colon; whereas the area of NADPH-diaphorase positive fibers, in the circular muscle layer, was decreased in the acetic acidtreated groups. These results suggest that NO-mediated inhibitory neural input, to the circular muscle, was decreased in the acetic acid-treated groups.
Acetic Acid/toxicity ; Animals ; Colitis/chemically induced/*pathology/*physiopathology ; Colon/drug effects/enzymology/*innervation/pathology ; Indicators and Reagents/toxicity ; Male ; Muscle Contraction/drug effects ; Muscle, Smooth/drug effects/metabolism ; Myenteric Plexus/pathology ; NADPH Dehydrogenase/metabolism ; NG-Nitroarginine Methyl Ester/pharmacology ; Neuromuscular Junction/drug effects/*metabolism ; Nitrergic Neurons/drug effects/*metabolism ; Nitric Oxide/*metabolism ; Peroxidase/metabolism ; Potassium Chloride/pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effect of NOD2 on colitis pathogenesis in experimental rats, and discuss therapeutical effect and mechanism of kushenin injection (OMT) on colitis in experimental rats.

METHODFourty Sprague-Dawley (SD) rats were randomly divided into four groups: the normal control group, the model group, the SASP group, and the OMT group, with 10 rats in each group. Except the normal control group, models were established in the remaining three groups with TNBS. The OMT group was injected with kushenin injection, the SASP group was orally administered with mesalazine suspension, the model group and the normal group were orally administered with distilled water for 15 days. Colon lesion score and histological score of experimental rats were observed. Expression of NOD2, NF-kappaB p65 protein in rats colonic mucous was detected by immunohistochemistry. Expression of IL-6 in rat colon mucous was detected by ELISA.

RESULTCompared with normal control group, the expression of NOD2, NF-kappaB p65 and IL-6 in colonic mucosa of the model group were significantly increased (P < 0.01). The SASP group and the OMT group showed lower expressions of NOD2, NF-kappaB p65 and IL-6 in colonic mucosa than the model group (P < 0.01, P < 0.05).

CONCLUSIONThe over expression of colonic mucosa proteins NOD2 and NF-kappaB p65 and increasing secretion of IL-6 take part in the appearance and development of ulcerative colitis. OMT can attenuate ulcerative colitis and protect colonic mucosa by inhibiting expression of NOD2, NF-kappaB p65 and decreasing IL-6.

Animals ; Colitis ; metabolism ; pathology ; physiopathology ; prevention & control ; Colon ; drug effects ; metabolism ; pathology ; physiopathology ; Eating ; drug effects ; Gene Expression Regulation ; drug effects ; Injections ; Intestinal Mucosa ; drug effects ; metabolism ; pathology ; physiopathology ; Male ; Nod2 Signaling Adaptor Protein ; metabolism ; Organ Size ; drug effects ; Pterocarpans ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Transcription Factor RelA ; metabolism

OBJECTIVETo observe the therapeutic effect of Chinese compound, Changlu Enema (CE), on immune ulcerative colitis (UC) in mice.

METHODSMice were randomly divided into the normal group, the model group, the CE high dose (CE-H) and low dose (CE-L) group and the salicylazosulfapyridine (SASP) group. All mice, except those in the normal group, were made into UC model by colonic mucosa protein immunization. After 21 days of medication, the changes of UC activity index and body weight in mice were observed, and the condition of colonic inflammation and histomorphological changes in colonic tissue were observed also.

RESULTSUC activity index was lower and body weight was higher in the two CE groups than those in the model group respectively, showing significant difference (P < 0.05 or P < 0.01); pathological examination showed the pathological changes and inflammatory response in colonic tissue were relieved significantly after treatment, and the improvement in the CE-H group was better than that in the SASP group.

CONCLUSIONTCM compound CE is markedly effective in treating UC rats.

Administration, Rectal ; Animals ; Colitis, Ulcerative ; drug therapy ; immunology ; Colon ; drug effects ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Male ; Mice ; Phytotherapy ; Random Allocation ; Treatment Outcome

OBJECTIVETo explore the significance of colonic epithelial cell apoptosis and tumor necrosis factor α (TNF-α) changing in pathogenesis of melanosis coli (MC) in guinea pig and the molecular mechanism of rhubarb (Rhu) in inducing the disease, by means of using different dosages of Rhu to induce the disease.

METHODSOne hundred and forty-four male guinea pigs, clean grade, were randomized according to their body weight into 5 groups, the untreated normal group and the 4 Rhu groups treated, respectively, with different doses of Rhu, 3 g/kg·d for low dose (Rhu-l) group, 6 g/kg·d for moderate dose (Rhu-m) group, 12 g/kg·d for high dose (Rhu-h) group and 24 g/kg·d for super-high dose (Rhu-s) group via gastric infusion. All animals were sacrificed 60 days later, their viscera were taken for observing the pathologic and morphologic changes with HE, melanin and melatonin staining, and the apoptosis of colonic epithelial cells was detected with TUNEL stain and transmission electric microscopy. In addition, the levels of TNF-α in serum and colonic tissue were measured using ELISA and RT-PCR.

RESULTSThe pathological changes of MC could be found by naked eye in all Rhu groups, especially apparent at caecum and proximal end of colon, but did not found in gallbladder, jejunum and ileum. In normal guinea pigs, the colonic membrane was pink in color with no apparent pigment deposition. Membranous color deepened in the Rhu groups depending on the dosage of Rhu used. MC scoring showed the highest scores revealed in the Rhu-s group (6.00±0.00), which was significantly different to those in the Rhu-l (3.86±0.69), Rhu-m (4.43±0.79) and Rhu-h groups (4.88±0.35, all P<0.05). Levels of cell apoptosis in colon and TNF-α in serum in all Rhu groups were higher than those in the normal group (P<0.01), but showed no significant difference among the Rhu groups (P>0.05). Moreover, a positive correlation was found in the degree of induced MC with apoptosis rate and TNF-α level.

CONCLUSIONSRhu (anthraquinone purgatives) had apparent effect on inducing MC; its molecular mechanism is maybe to destroy intestinal mucosal barrier and advance proinflammatory factor TNF-α releasing, which leads to colonic epithelial cells apoptosis, and finally induce the change of MC due to the deposition of brown pigments, i.e. the macrophage phagocytized apoptotic body, on the colonic membrane.

Animals ; Anthraquinones ; adverse effects ; Apoptosis ; drug effects ; Cathartics ; adverse effects ; Colon ; pathology ; ultrastructure ; Colonic Diseases ; blood ; chemically induced ; complications ; pathology ; Epithelial Cells ; drug effects ; pathology ; Gene Expression Regulation ; drug effects ; Guinea Pigs ; In Situ Nick-End Labeling ; Male ; Melanosis ; blood ; chemically induced ; complications ; pathology ; RNA, Messenger ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; blood ; genetics