mycophenolic-acid and Intestinal-Diseases

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antineoplastic Agents; Cathartics; Colchicine; Contraceptives, Oral; Diuretics; Ergotamine; Esophagitis; Humans; Imidazoles; Intestinal Diseases; Ion Exchange Resins; Iron; Laxatives; Mycophenolic Acid; Olmesartan Medoxomil; Stomach Diseases; Tetrazoles

Topics: Adult; Arterioles; Blood Pressure; Cyclosporine; Diarrhea; Drug Resistance; Drug Therapy, Combination; Eye Diseases, Hereditary; Female; Fibrosis; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Hyalin; Immunosuppressive Agents; Intestinal Diseases; Male; Mycophenolic Acid; Prednisolone; Prospective Studies; Proteinuria; Skin Abnormalities; Treatment Outcome; Vascular Diseases

Schisandra sphenanthera Rehder & E.H. Wilson (S. sphenanthera) is a botanical medicine included in the 2020 edition of the ChP that has a variety of medicinal activities, including hepatoprotective, anticancer, antioxidant and anti-inflammatory properties. Wuzhi capsule (WZ) is a proprietary Chinese medicine made from an ethanolic extract of S. sphenanthera that is commonly used to treat drug-induced liver injury. However, there are no research reports exploring the effects of WZ on the prevention of mycophenolate mofetil (MMF)-induced intestinal injury and its underlying mechanisms.. This experiment aimed to evaluate the ameliorative effect of WZ on MMF-induced intestinal injury in mice and its underlying mechanisms.. A mouse model of MMF-induced intestinal injury was established and treated with WZ during the 21-day experimental period. The pathological characteristics of the mouse ileum were observed. Tight junction (TJ) protein changes were observed after immunofluorescence staining and transmission electron microscopy, and ROS levels were measured by using DHE fluorescent dye and the TUNEL assay for apoptosis. The expression of p65, p-p65, IκBα, p-IκBα, the TJ proteins occludin and ZO-1 and the apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3 and caspase-3 were analysed by Western blot. Levels of DAO, ET, TNF-α, IL-1β, IL-6, IFN-γ, MDA and SOD were analysed by using kits.. MMF activated the NF-κB signaling pathway to cause intestinal inflammation, increased intestinal permeability, changed the expression of TJ protein in the intestinal epithelium, and increased oxidative stress and apoptosis levels. WZ significantly downregulated the expression of p-p65 and p-IκBα to relieve the inflammatory response, reduced intestinal permeability, maintained intestinal TJ protein expression, and reduced intestinal oxidative stress and apoptosis.. Our research suggested that MMF can cause intestinal injury; by contrast, WZ may exert anti-inflammatory, antioxidant and apoptosis-reducing effects to alleviate MMF-induced intestinal injury.

Topics: Animals; Animals, Outbred Strains; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Drugs, Chinese Herbal; Immunosuppressive Agents; Inflammation; Intestinal Diseases; Intestinal Mucosa; Intestines; Male; Mice; Mycophenolic Acid; Oxidative Stress

Mycophenolic acid (MPA) is the most widely used immunosuppressive drug in transplantation and for autoimmune diseases. Unfortunately, more than 30% of patients experience a typical gastrointestinal adverse effect also referred to as mycophenolate-induced enteropathy. Due to its antibacterial, antifungal, and antiviral properties, MPA exposure is associated with intestinal dysbiosis characterized by a decrease in density and diversity of the microbiome regarding the main bacterial phyla (Firmicutes and Bacteroidetes). These bacterial phyla are known for their metabolic role in maintaining the homeostasis of the digestive tract, particularly through the production of short-chain fatty acids (SCFA) that could contribute to the pathophysiology of mycophenolate-induced enteropathy. Our study aimed at deciphering short-chain fatty acids (SCFA) profile alterations associated with gastrointestinal toxicity of MPA at the digestive and systemic levels in a mouse model.. Ten-week old C57BL/6 (SOPF) mice were randomly assigned in 2 groups of 9 subjects: control, and mycophenolate mofetil (MMF, 900 mg/kg/day). All mice were daily treated by oral gavage for 7 days. Individual faecal pellets were collected at days 0, 4 and 8 as well as plasma at day 8 for SCFA profiling. Additionally, after the sacrifice on day 8, the caecum was weighted, and colon length was measured. The proximal colon was cut for histological analysis.. MMF treatment induced around 10% weight loss at the end of the protocol associated with a significant decrease in caecum weight and a slight reduction in colon length. Histological analysis showed significant architectural changes in colon epithelium. Moreover, we observed an overall decrease in SCFA concentrations in faecal samples, especially regarding acetate (at day 8, control 1040.6 ± 278.161 μM versus MMF 384.7 ± 80.5 μM, p < 0.01) and propionate (at day 8, control 185.94 ± 51.96 μM versus MMF 44.07 ± 14.66 μM, p < 0.001), and in plasma samples for butyrate (at day 8, control 0.91 ± 0.1 μM versus MMF 0.46 ± 0.1 μM, p < 0.01).. These results are consistent with functional impairment of the gut microbiome linked with digestive or systemic defects during MMF treatment.

Topics: Animals; Anti-Bacterial Agents; Colon; Disease Models, Animal; Fatty Acids, Volatile; Feces; Female; Gastrointestinal Microbiome; Immunosuppressive Agents; Intestinal Diseases; Mice, Inbred C57BL; Mycophenolic Acid

Graft-versus-host disease (GvHD) is a multi-organ disease caused by mature donor T cells that are activated by alloantigens expressed by the host antigen-presenting cells. GvHD has been reported after solid organ transplantation with two principal presentations: humoral and cellular. In the cellular type of GvHD after liver transplantation the symptoms are identical to the GvHD after bone marrow transplant, except that the liver is spared because it lacks host antigens. We have described three cases of intestinal GvHD after pediatric liver transplant with an unusual recurrent late presentation in two patients. Two patients were female, and their age at the time of transplant was 8 and 9 months, respectively, and one was an 8-month-old male. They all received reduced liver allografts of identical blood type from three different donors. One patient received two doses of donor bone marrow cell infusion. Two patients received double immunosuppressive therapy constituted by tacrolimus at a dose of 0.05 mg/kg p.o. b.i.d. and steroids 10 mg p.o. daily. One patient received a triple drug immunosuppression with tacrolimus (0.05 mg/kg p.o. b.i.d.), steroids (10 mg p.o. daily) and mycophenolate mofetil (125 mg p.o. b.i.d.). Diagnosis of intestinal GvHD was confirmed histologically on intestinal biopsies performed at the time of presentation of the clinical symptoms or at autopsy.

Topics: Adolescent; Adrenal Cortex Hormones; Biopsy; Bone Marrow Transplantation; Child; Colon; Colon, Sigmoid; Duodenum; Female; Follow-Up Studies; Graft vs Host Disease; Humans; Immunosuppressive Agents; Infant; Intestinal Diseases; Intestines; Liver Transplantation; Male; Mycophenolic Acid; Recurrence; Tacrolimus; Time Factors; Tissue Donors