Chitosan oligosaccharide (COS), a natural polysaccharide with good antioxidant and anti-inflammatory properties, is the depolymerized product of chitosan possessing various biological activities. The present study was designed to investigate the possible anti-aging effect of COS on the aging model mouse induced by d-galactose (d-gal) and explore the underlying mechanism. In the experiment, 48 male Kunming mice (KM mice) were randomly divided into the normal group, model group, positive group, and low-medium-high dose polysaccharide groups (300, 600, 1200 mg/kg/day). The results showed that COS, by intragastric gavage after subcutaneous injection of d-gal (250 mg/kg/day) into the neck of mice consecutively for eight weeks, gradually recovered the body weight, the activity of daily living, and organ indices of mice, as well as effectively ameliorated the histological deterioration of the liver and kidney in mice triggered by d-gal. To be specific, COS obviously improved the activities of antioxidant enzymes in liver and kidney of KM mice, including catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), as well as decreased malondialdehyde (MDA) levels when compared with those in model group mice. Furthermore, COS not only elevated the diminished levels of serum immunoglobulin G (IgG) and IgM induced by d-gal, but also significantly inhibited the d-gal-caused upregulation of serum alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), uric acid (UA) and creatinine (CREA) levels as compared with those of mice in the model group. These results demonstrate that COS has an obvious anti-aging activity in d-gal-induced subacute aging mice, the mechanism of which, to some extent, is associated with enhancing the antioxidant defenses, reducing oxidative stress, and improving the immune function of aging model mice.

Background: Lamotrigine plays a crucial role in the treatment of epilepsy and bipolar disorder in adults and children. However, its pharmacokinetic (PK) behavior in first or long-term treatment in pediatric patients and the changes in drug exposure in patients with renal impairment are not well characterized. The purpose of the research was to build a robust physiologically based pharmacokinetic (PBPK) model of lamotrigine for the prediction of drug exposure in diverse populations to facilitate therapeutic drug monitoring (TDM) and guide dosing regimens. Methods: The physicochemical parameter values of lamotrigine were integrated to establish and validate the model in an adult population in PK-sim. This adult PBPK model can be extrapolated to children and patients with renal impairment to predict PK changes. Results: Most of the observed data were within the 5th and 95th percentile intervals of the variability around the predicted plasma concentrations. The model predicted pharmacokinetic thresholds and exposure values for clinically safe and effective doses recommended by the FDA for initial and long-term treatment of epilepsy in adults and children aged 2–12 years. Notably, patients with severe renal impairment and end-stage renal disease experienced an average increase in the area under the curve of 1.51 folds and 1.62 folds, respectively. This scenario necessitates further lamotrigine dose adjustments. Conclusions: The developed lamotrigine PBPK model offers a strategy for assisting clinicians in TDM and dose adjustment for special populations, thereby offering a reference (PK parameters, as well as peak and valley concentrations to reach a steady state) for a safer administration regimen in clinical treatment.