Biology subjects

Joja, M.

Publications and source records attributed to Joja, M..

5 recordsLinked to original sources

bioRxiv2022

Altered secretion, constitution, and functional properties of the gastrointestinal mucus in a rat model of sporadic Alzheimer's disease

Accumulating evidence supports the involvement of the gastrointestinal (GI) system in Alzheimers disease (AD), however, it is currently unknown whether GI alterations arise as a consequence of central nervous system (CNS) pathology or play a causal role in the pathogenesis of the disease. The GI mucus system is a possible mediator of GI dyshomeostasis in neurological disorders as CNS controls mucus production and secretion via the efferent arm of the brain-gut axis. The aim was to use a brain-first model of sporadic AD induced by intracerebroventricular streptozotocin (STZ-icv) to dissect the efferent (i.e. brain-to-gut) effects of isolated central neuropathology on the GI mucus system. Quantification and morphometric analysis of goblet cell mucigen granules revealed altered GI mucus secretion in the AD model possibly mediated by the insensitivity of AD goblet cells to neurally-evoked mucosal secretion confirmed by ex vivo cholinergic stimulation of isolated duodenal rings. The dysfunctional efferent control of the GI mucus secretion results in altered biochemical composition of the mucus associated with reduced glycoprotein aggregation and binding capacity in vitro. Finally, functional consequences of the reduced barrier-forming capacity of the AD mucus are demonstrated using the in vitro two-compartment caffeine diffusion interference model. Isolated central AD-like neuropathology results in the loss of efferent control of GI homeostasis via the brain-gut axis characterized by the insensitivity to neurally-evoked mucosal secretion, altered mucus constitution, and reduced barrier-forming capacity potentially increasing the susceptibility of STZ-icv rat model of AD to GI and systemic inflammation induced by intraluminal toxins, microorganisms, and drugs.

neuroscience↗

bioRxiv2022

The absence of gastrointestinal redox dyshomeostasis in the brain-first rat model of Parkinson's disease induced by bilateral intrastriatal 6-hydroxydopamine

The gut-brain axis plays an important role in Parkinsons disease (PD) by acting as a route for vagal propagation of aggregated -synuclein in the gut-first endophenotype and as a mediator of gastrointestinal dyshomeostasis via the nigro-vagal pathway in the brain-first endophenotype of the disease. One important mechanism by which the gut-brain axis may promote PD is by regulating gastrointestinal redox homeostasis as overwhelming evidence suggests that oxidative stress plays a key role in the etiopathogenesis and progression of PD and the gastrointestinal tract maintains redox homeostasis of the organism by acting as a critical barrier to environmental and microbiological electrophilic challenges. The present aim was to utilize the bilateral intrastriatal 6-hydroxydopamine (6-OHDA) brain-first PD model to study the effects of isolated central pathology on redox homeostasis of the gastrointestinal tract. Three-month-old male Wistar rats were either not treated (intact controls; CTR) or treated bilaterally intrastriatally with vehicle (CIS) or 6-OHDA (6-OHDA). Motor deficits were assessed with the rotarod performance test and the duodenum, ileum, and colon were dissected for biochemical analyses 12 weeks after the treatment. Lipid peroxidation, total antioxidant capacity, low-molecular thiols, and protein sulfhydryls, the activity of total and Mn/Fe superoxide dismutases, and total and azide-insensitive catalase/peroxidase were measured. Univariate and multivariate models of redox biomarkers provide solid evidence against the existence of pronounced gastrointestinal redox dyshomeostasis. The results indicate that the dysfunction of the nigro-vagal system and not motor deficit may be a key mediator of gastrointestinal dyshomeostasis in brain-first 6-OHDA-induced rodent models of PD.

neuroscience↗

bioRxiv2022

Sudan black lipid blot - a rapid and simple method for quantification of lipids in biological samples

Bioanalytical techniques for the isolation and quantification of total lipids in biological samples are an integral part of lipidomic workflows and widely used tools for metabolic assessment at the cellular and organismic levels. The most widely used protocol for the isolation, extraction, and quantification of total lipids in biological tissues was originally introduced by Folch et al.. It requires a relatively large amount of tissue and large volumes of lipid extracts for reliable assessment of lipid content using the gravimetric technique. Here, we propose a new method to overcome the aforementioned challenges based on the hypothesis that the partitioning coefficient of the widely used lysochrome diazo dye Sudan Black B between the lipid extract and ethylene glycol can be used to indirectly estimate the absolute concentration of lipids. The proposed method demonstrates great precision and linearity, requires minimal equipment, and enables the analysis of total lipid content in biological specimens available only in limited amounts by reducing the requirements for the input quantity by >300-fold for some tissues (e.g. fecal samples).

biochemistry↗

bioRxiv2022

Non-alcoholic components of Pelinkovac, a Croatian wormwood-based strong liquor, counteract the inhibitory effect of high ethanol concentration on catalase in vitro

Antioxidant enzyme catalase protects the cells against alcohol-induced oxidative stress by scavenging free radicals and metabolizing alcohol. Concentrations of ethanol present in alcoholic beverages can inhibit catalase and foster oxidative stress and alcohol-induced injury. Non-alcoholic components of pelinkovac counteract the inhibitory effects of high ethanol concentration and acidic pH on catalase in vitro.

pharmacology and toxicology↗

bioRxiv2021

The effect of acute oral galactose administration on the redox system of the rat small intestine

Galactose is a ubiquitous monosaccharide with important yet incompletely understood nutritive and physiological roles. Chronic parenteral D-galactose administration is used for modeling aging-related pathophysiological processes in rodents due to its ability to induce oxidative stress (OS). Conversely, chronic oral D-galactose administration prevents and alleviates cognitive decline in a rat model of sporadic Alzheimers disease indicating galactose may exert beneficial health effects by acting in the gut. The present aim was to explore acute time-response of intestinal redox homeostasis following oral administration of D-galactose. Male Wistar rats were euthanized at baseline (n=6), 30 (n=6), 60 (n=6), and 120 (n=6) minutes following orogastric administration of D-galactose (200 mg/kg). The overall reductive capacity, lipid peroxidation, the concentration of low molecular weight thiols (LMWT) and protein sulfhydryls (SH), the activity of Mn and Cu/Zn superoxide dismutases (SOD), reduced and oxidized fractions of nicotinamide adenine dinucleotide phosphates (NADPH/NADP), and hydrogen peroxide dissociation rate were analyzed in duodenum and ileum. Acute oral administration of D-galactose increased the activity of SODs and decreased intestinal lipid peroxidation and nucleophilic substrates (LMWT, SH, NADPH) indicating activation of peroxidative damage defense pathways. The redox system of the small intestine can acutely tolerate even high luminal concentrations of galactose (0.55 M) and oral galactose treatment is associated with a reduction rather than the increment of the intestinal OS. The ability of oral D-galactose to modulate intestinal OS should be further explored in the context of intestinal barrier maintenance, and beneficial cognitive effects associated with long-term administration of low doses of D-galactose.

biochemistry↗