Safety assessment of desaminotyrosine: Acute, subchronic oral toxicity, and its effects on intestinal microbiota in rats.

In this work, the acute and subchronic toxicities of desaminotyrosine (DAT) by oral administration in SD rats and its effects on the intestinal microflora were investigated. The acute toxicity test showed that DAT is a low-toxic substance with a LD50 of 3129 mg/kg. The subchronic toxicity test showed that DAT has no toxicity at a low dose (125 mg/kg/day). However, DAT exhibited obvious toxicities to food intake, liver, kidney, and lung at higher dose (250 mg/kg/day and 500 mg/kg/day). DAT inhibited the food intake of rats in a dose-dependent manner. Serum biochemical analysis showed that DAT can increase the serum glucose level of rats. Fecal microbiota analysis showed that DAT treatment can significantly change the intestinal microflora of rats, the dose of 125 mg/kg/day has the most significant effect on the diversity of intestinal microbiota. In daily application, the side effects caused by DAT might be gastrointestinal irritation, weight loss, liver or kidney injury, and blood sugar elevation. Based on our study, the no-observed-adverse-effect level (NOAEL) of DAT is 125 mg/kg BW/day for rats.

Transglutaminase-catalyzed preparation of crosslinked carboxymethyl chitosan/carboxymethyl cellulose/collagen composite membrane for postsurgical peritoneal adhesion prevention.

Peritoneal adhesion is a general complication following pelvic and abdominal surgery, which may lead to chronic abdominal pain, bowel obstruction, organ injury, and female infertility. Biodegradable polymer membranes have been suggested as physical barriers to prevent peritoneum adhesion. In this work, a transglutaminase (TGase)-catalyzed crosslinked carboxymethyl chitosan/carboxymethyl cellulose/collagen (CMCS/CMCL/COL) composite anti-adhesion membrane with various proportions of CMCS, CMCL, and COL (40/40/20, 35/35/30, 25/25/50) was developed. After crosslinking by TGase, the composite anti-adhesion membranes shown enhanced mechanical properties and improved biodegradability. Meanwhile, the high cytocompatibility of anti-adhesion membranes was proved by in vitro cell culture study. Moreover, the anti-adhesion membrane with the proportion of 25/25/50 was implanted between the artificially defected cecum and peritoneal wall in rats and following by general observation, histological examination, and inflammatory factors assay. The results indicated that the anti-adhesion membrane can significantly prevent peritoneal adhesion with negligible immunogenicity. Therefore, the composite membrane crosslinked by TGase had satisfactory anti-adhesive effects with high biocompatibility and low antigenicity, which could be used as a preventive barrier for peritoneal adhesion.