Biology subjects

Samal, T.

Publications and source records attributed to Samal, T..

3 recordsLinked to original sources

bioRxiv2026

Restoration of Redox Homeostasis and Endogenous Aldehyde Detoxification by UT-018 Following Acute Ethanol Exposure

Alcohol-induced toxicity is driven largely by the accumulation of acetaldehyde and disruption of hepatic redox homeostasis during ethanol metabolism. Oxidation of ethanol by alcohol dehydrogenase (ADH) consumes nicotinamide adenine dinucleotide (NAD) while generating NADH, shifting the intracellular redox state toward a highly reduced environment that impairs mitochondrial function, limits endogenous aldehyde dehydrogenase (ALDH)-mediated acetaldehyde clearance, and promotes oxidative stress and tissue injury. We investigated whether UT-018, a novel metabolic intervention, could support endogenous metabolic resilience during acute ethanol exposure using complementary in vitro and in vivo models. Mechanistic in vitro studies evaluated ADH-dependent NADH generation and NAD add-back experiments, while in vivo investigations assessed serum ALDH-associated activity, circulating acetaldehyde concentrations, and gross gastrointestinal and hepatic morphology following acute ethanol challenge. UT-018 reduced ethanol-associated NADH accumulation in a concentration-dependent manner without evidence of irreversible ADH inhibition. Restoration of NADH generation following supplementation with exogenous NAD demonstrated reversible modulation of ethanol-associated redox biology rather than direct enzymatic inhibition. In vivo, UT-018 enhanced serum ALDH-associated activity, reduced circulating acetaldehyde concentrations by approximately 27 to 33% compared with ethanol-treated controls. Metabolic biomarkers were accompanied by preservation of gross colon and liver morphology following acute ethanol exposure. Collectively, these findings support coordinated biological activity across multiple interconnected stages of alcohol metabolism and support a systems-level mechanism in which restoration of redox homeostasis enhances endogenous aldehyde detoxification, reduces acetaldehyde burden, and preserves tissue integrity. These results identify alcohol metabolism restoration as a promising strategy for enhancing physiological resilience to acute alcohol exposure and provide a rationale for further preclinical and clinical evaluation of UT-018. HighlightsO_LIUT-018 restored ethanol-associated redox homeostasis by reducing excessive NADH accumulation without irreversible inhibition of alcohol dehydrogenase in vitro. C_LIO_LIRestoration of redox balance was associated with enhanced endogenous aldehyde dehydrogenase (ALDH)-associated activity following acute ethanol exposure in vivo. C_LIO_LIUT-018 reduced circulating acetaldehyde concentrations by approximately 30%. C_LIO_LIThe metabolic homeostasis was accompanied by preservation of gross gastrointestinal and hepatic morphology in an acute ethanol challenge model. C_LIO_LIThe collective findings support a systems-level mechanism in which modulation of endogenous alcohol related metabolic pathways enhances physiological resilience to acute alcohol exposure. C_LI

pharmacology and toxicology↗

bioRxiv2026

Fructooligosaccharide Supplementation Improves Glucose Homeostasis in Human-Relevant hyperglycemic Diet-Induced Obese Mice

Fructooligosaccharides (FOS) are prebiotic fibers that influence gut microbiota and host metabolic function. In a diet-induced obesity (DIO) mouse study, FOS supplementation was compared with PBS-treated obese controls. Blood glucose was markedly lower at Day 42 (221.9 {+/-} 7.8 vs 138.3 {+/-} 9.0 mg/dL), and remained lower at Day 56. FOS reduced body-weight gain from 8.4 {+/-} 0.9 g in PBS controls to 2.6 {+/-} 0.2 g, corresponding to an approximate 69.5% reduction in gain over Days 1-70. Cumulative feed consumption was not significantly different between PBS and FOS cages, suggesting that the observed metabolic effects were not explained simply by reduced food intake. These data support our thesis that FOS works as an active metabolic ingredient acting through the gut-liver-metabolic axis. Thus, in the present study, dietary FOS supplementation produced marked improvements in glucose homeostasis in a severe DIO model characterized by diabetic-range hyperglycemia that more closely resembles poorly controlled human type 2 diabetes. HIGHLIGHTSO_LIFructooligosaccharide (FOS) normalized glucose levels in a severe DIO model that mimics poorly controlled human type 2 diabetes. C_LIO_LIDay-42 blood glucose was reduced by [~]37.7% in FOS-treated DIO mice. C_LIO_LIFOS reduced body-weight gain by [~]69.5% versus controls over 70 days. C_LIO_LIMetabolic benefits occurred without a statistically significant reduction in feed intake. C_LIO_LIFindings support a gut-liver-metabolic mechanism rather than simple caloric restriction. C_LIO_LIData position FOS as an active metabolic ingredient with potential utility in diabetes and metabolic health. C_LI

pharmacology and toxicology↗

bioRxiv2026

UT-018 Protects Collagen Extracellular Matrix Through Substrate-Directed Stabilization and Collagenase Modulation

Pathological collagen degradation is a central feature of impaired wound healing, dermal aging, periodontal breakdown, intestinal barrier injury and connective tissue degeneration. Current strategies often focus on direct inhibition of matrix metalloproteinases or collagenases; however, complete blockade of collagen remodeling may interfere with normal repair. UT-018, a bioactive formulation that acts as a tissue-protective and regenerative agent, was evaluated as a collagenous extracellular matrix modulator. Across in vitro kinetic assays, endpoint signal analysis, integrated area-under-curve (AUC) analysis and substrate preincubation studies, UT-018 produced concentration-dependent preservation of collagen against collagenase challenge. Importantly, collagen protection persisted after substrate preincubation with UT-018, with approximately 33%, 60% and 65% protection at 5, 10 and 25 mM UT-018 concentrations, respectively. Exploratory kinetic transformations did not support a simple competitive collagenase inhibitor model. Instead, the collective pattern supports a substrate-directed mechanism involving collagen shielding, reduced cleavage susceptibility and indirect modulation of collagenase activity. These findings position UT-018 as a potential first-in-class collagen resilience modulator for wound healing, gastrointestinal barrier protection, oral care, dermal preservation and regenerative medicine applications. Highlights- UT-018 preserves collagen content in in vitro collagenase challenge assays. - The Protection is UT-018 concentration-dependent across kinetic, endpoint and AUC readouts. - Preincubation of substrate with UT-018 retains protection after collagenase challenge. - The data support matrix-directed stabilization by UT-018 rather than classical active-site collagenase inhibition.

pharmacology and toxicology↗