The effect of Trolox on the rabbit anal sphincterotomy repair.

INTRODUCTION: Fecal incontinence (FI) is caused by external anal sphincter injury. Vitamin E is a potential strategy for anal sphincter muscle repair via its antioxidant, anti-inflammatory, anti-fibrotic, and protective properties against myocyte loss. Thus, we aimed to evaluate the water-soluble form of vitamin E efficacy in repairing anal sphincter muscle defects in rabbits. METHODS: Twenty-one male rabbits were equally assigned to the intact (without any intervention), control (sphincterotomy), and Trolox (sphincterotomy + Trolox administration) groups. Ninety days after sphincterotomy, the resting and squeeze pressures were evaluated by manometry, and the number of motor units in the sphincterotomy site was calculated by electromyography. Also, the amount of muscle and collagen in the injury site was investigated by Mallory's trichrome staining. RESULTS: Ninety days after the intervention, the resting and squeeze pressures in the intact and Trolox groups were significantly higher than in the control group (P = 0.001). Moreover, the total collagen percentage of the sphincterotomy site was significantly lower in the Trolox group than in the control group (P = 0.002), and the total muscle percentage was significantly higher in the Trolox group compared to the control group (P = 0.001). Also, the motor unit number was higher in the Trolox group than in the control group (P = 0.001). CONCLUSION: Trolox administration in the rabbit sphincterotomy model can decrease the amount of collagen and increase muscle, leading to improved anal sphincter electromyography and manometry results. Therefore, Trolox is a potential treatment strategy for FI.

Metabolism of vertebrate amino sugars with N-glycolyl groups: resistance of α2-8-linked N-glycolylneuraminic acid to enzymatic cleavage.

The sialic acid (Sia) N-acetylneuraminic acid (Neu5Ac) and its hydroxylated derivative N-glycolylneuraminic acid (Neu5Gc) differ by one oxygen atom. CMP-Neu5Gc is synthesized from CMP-Neu5Ac, with Neu5Gc representing a highly variable fraction of total Sias in various tissues and among different species. The exception may be the brain, where Neu5Ac is abundant and Neu5Gc is reported to be rare. Here, we confirm this unusual pattern and its evolutionary conservation in additional samples from various species, concluding that brain Neu5Gc expression has been maintained at extremely low levels over hundreds of millions of years of vertebrate evolution. Most explanations for this pattern do not require maintaining neural Neu5Gc at such low levels. We hypothesized that resistance of α2-8-linked Neu5Gc to vertebrate sialidases is the detrimental effect requiring the relative absence of Neu5Gc from brain. This linkage is prominent in polysialic acid (polySia), a molecule with critical roles in vertebrate neural development. We show that Neu5Gc is incorporated into neural polySia and does not cause in vitro toxicity. Synthetic polymers of Neu5Ac and Neu5Gc showed that mammalian and bacterial sialidases are much less able to hydrolyze α2-8-linked Neu5Gc at the nonreducing terminus. Notably, this difference was not seen with acid-catalyzed hydrolysis of polySias. Molecular dynamics modeling indicates that differences in the three-dimensional conformation of terminal saccharides may partly explain reduced enzymatic activity. In keeping with this, polymers of N-propionylneuraminic acid are sensitive to sialidases. Resistance of Neu5Gc-containing polySia to sialidases provides a potential explanation for the rarity of Neu5Gc in the vertebrate brain.