Search Results (3,757)

The global obesity epidemic is expanding at an alarming rate, posing significant health risks for women of reproductive age due to immediate pregnancy complications and adverse long-term effects on offspring. Consequently, several non-pharmacological strategies have been proposed to mitigate these impacts. Therefore, we hypothesized that the combined application of the probiotic Lacticaseibacillus rhamnosus GG (LGG) and enriched environment (EE) will result in improved metabolic and histopathologic findings within a model of maternal obesity, surpassing the efficacy of individual therapeutic strategies. Using nulliparous Wistar rats, LGG was administered before, during, and after gestation, while EE was implemented during pregnancy and lactation. LGG supplementation and an enriched environment separately improved blood triacylglycerols. The enriched environment was more effective in reducing the effects of maternal obesity, even lessening liver damage observed in obese subjects in the form of vacuolar infiltrates. The results obtained suggest a potential functional interaction in this combined model, and the findings indicate that LGG may have influenced the modulation of enriched environment effects on metabolic parameters. Diet, probiotic supplementation, and environmental setting during the perinatal period have specific effects on biochemical and tissular parameters, establishing their descriptive role as non-pharmacological intervention strategies and underscoring the need for mechanistic studies to elucidate the biological pathways underlying these effects. Full article

Severe subacute exposure to aluminium chloride (AlCl₃) impairs renal function and induces cortical tubular injury; however, the concomitant balance between injury and repair in tubular epithelia remains incompletely defined. Accordingly, we aimed to use a high-dose regimen of AlCl₃ (100 mg·kg⁻¹·day⁻¹ for 30 days, oral gavage) as a standardised renal stressor in male Wistar rats to quantify shifts along the injury–repair balance in the renal cortex and to test whether L-carnitine (LC) pretreatment (200 mg·kg⁻¹·day⁻¹) can attenuate these shifts. Twenty rats were assigned to four groups: control, LC alone, AlCl₃ alone, and LC followed 60 min later by AlCl₃. On day 31, we assessed body-weight gain, renal functional markers, blinded cortical lesion scoring, quantitative histochemistry, and immunohistochemical profiling of cleaved caspase-3 (apoptotic signalling) and Ki-67 (proliferative engagement) within the same cortical compartment. AlCl₃ exposure produced a severe renal stress phenotype compared with controls, reducing body-weight gain from 99.8 ± 8.6 to 24.0 ± 8.3 g and increasing serum urea and creatinine from 26.40 ± 3.21 to 48.60 ± 5.81 mg/dL and from 0.606 ± 0.063 to 0.956 ± 0.147 mg/dL, respectively. Cortical injury increased from 0 (0–0) in controls to 15 (15–15) after AlCl₃ exposure. AlCl₃ also reduced strong PAS area from 97.92 ± 1.10% to 52.37 ± 14.68% and protein optical density from 0.353 ± 0.020 to 0.269 ± 0.039, while increasing collagen area fraction from 6.92 ± 1.67% to 18.40 ± 3.02% and cleaved caspase-3 from 1.0 (1.0–2.0) to 12.0 (12.0–12.0). Ki-67 labelling declined from 17.80 ± 3.35% to 6.00 ± 1.58%, indicating suppressed proliferative engagement. Compared with AlCl₃ alone, LC pretreatment showed partial protection, with higher body-weight gain (70.0 ± 15.6 g), lower serum urea and creatinine (21.40 ± 2.30 mg/dL and 0.580 ± 0.084 mg/dL), lower cortical injury burden [3 (3–4)], greater strong PAS area (89.25 ± 2.67%), higher protein optical density (0.354 ± 0.012), lower collagen area fraction (12.26 ± 1.70%), lower cleaved caspase-3 [4.0 (4.0–6.0)], and higher Ki-67 labelling (10.60 ± 2.30%). Residual cortical injury, persistent collagen elevation, and incomplete Ki-67 preservation indicate that LC pretreatment attenuated, but did not fully prevent, AlCl₃-induced renal cortical alterations. Overall, high-burden AlCl₃ exposure not only enhanced cell loss but also impaired regenerative renewal, whereas LC pretreatment partially preserved this injury–repair balance. Full article

Background/Objectives: Elevated homocysteine (Hcy) levels are associated with endothelial dysfunction, oxidative stress, and inflammation, contributing to cardiovascular disease development. The aim of this study was to examine the effects of vitamin B6 and folic acid on cardiometabolic biomarkers, cardiac oxidative stress, metabolic enzyme activities and cardiovascular histomorphometric parameters in homocysteine-loaded rats. Methods: Male Wistar albino rats were divided into four groups (n = 10, per group): C—saline 0.2 mL/day s.c. + saline 0.5 mL i.p; H: Hcy 0.45 µmol/g b.w./day s.c. + saline 0.5 mL i.p; C-B6+FA—saline 0.2 mL/day s.c. + vitamin B6 (7 mg/kg b.w. i.p./day) and folic acid (FA) (5 mg/kg b.w. i.p./day); and H-B6+FA—Hcy (0.45 µmol/g b.w./day s.c.) + vitamin B6 (7 mg/kg b.w. i.p./day) and FA (5 mg/kg b.w. i.p./day). Substances were applied s.c. for 2 weeks and i.p for 4 weeks. Results: B6+FA supplementation significantly reduced serum Hcy and LDL concentrations and attenuated Hcy-associated increases in cardiac SOD activity and right ventricular wall thickness. However, B6+FA was associated with increased cardiac MDA levels. MDH activity increased mainly in non-Hcy-loaded supplemented rats, whereas LDH activity, the cardio-somatic index, and aortic histomorphometric parameters remained unchanged. Conclusions: Combined B6+FA supplementation may improve Hcy metabolism, the LDL profile, and selected cardiac structural/oxidative alterations, but its association with increased lipid peroxidation suggests complex redox effects requiring cautious interpretation. Full article

Diabetic wounds remain a major clinical challenge due to impaired healing associated with persistent inflammation, oxidative stress, and microvascular dysfunction. Plasma-based therapies have emerged as promising approaches for promoting tissue repair; however, comparative evidence regarding different plasma modalities remains limited. In this study, we evaluated and compared the effects of atmospheric pressure cold plasma (APCP) and plasma-activated water (PAW) on wound healing in a streptozotocin-induced diabetic rat model. Forty Wistar albino rats were randomly assigned to five groups: isotonic wet dressing, hydrocolloid dressing, APCP treatment, PAW application, and a non-diabetic control group. Wound healing was assessed using macroscopic evaluation, histopathological analysis, and biochemical measurements of systemic oxidative status. PAW treatment significantly accelerated wound closure during the early healing phase compared with conventional dressing methods (p < 0.05). Histological findings demonstrated enhanced re-epithelialization, increased collagen deposition, and improved follicular regeneration in the PAW group. Although total oxidant status (TOS) did not differ significantly among groups (p = 0.996), total antioxidant status (TAS) was significantly increased following PAW treatment (p < 0.05), indicating a more favorable systemic antioxidant profile. These findings suggest an association between improved wound healing and a more favorable systemic antioxidant profile following PAW treatment. However, because local wound-level redox parameters and molecular markers were not assessed, the contribution of redox-related mechanisms remains to be clarified. Moreover, PAW demonstrated superior therapeutic efficacy compared with direct plasma application, highlighting its potential as a non-invasive approach for diabetic wound management. Full article

Early-life factors influence adult-brain vulnerability to sporadic Alzheimer’s disease (AD), but the underlying molecular mechanisms are unknown. In this study, we performed an integrated analysis of mitogen-activated protein kinases (MAPK) pathways’ (ERK1/2, JNK, and p38 MAPK) activity in the hippocampus and prefrontal cortex of OXYS rats (a model of sporadic AD) on postnatal days 3 and 10 (P3 and P10): critical periods of brain maturation. Wistar rats (healthy controls) showed extensive developmental transcriptional remodeling of all MAPK pathways. OXYS rats exhibited alterations, most pronounced in the prefrontal cortex at P3, with the JNK pathway showing the greatest divergence. At the protein level, OXYS rats failed to show the normal age-related increase in hippocampal ERK1/2 phosphorylation and in JNK1/2 levels in both regions, indicating developmental signaling deficits. p38 MAPK remained stable among Wistar and OXYS rats. Thus, delayed brain maturation, which contributes to accelerated brain aging and neurodegeneration in OXYS rats, occurs simultaneously with alterations in MAPK signaling. These aberrations potentially are able to increase brain susceptibility to age-related pathologies later in life. Full article

Neonatal hyperoxia induces oxidative stress that disrupts neurodevelopmental processes. While dexmedetomidine (DEX) exhibits acute neuroprotective properties, its long-term impact on developmental trajectories during recovery remains incompletely understood. This study examined whether a single neonatal dose of DEX modulates hippocampal neurogenesis following hyperoxia across defined postnatal stages. Six-day-old Wistar rats were exposed to 80% oxygen for 24 h and evaluated at postnatal days (P) 9, 11, and 14 after recovery in room air. Mechanistically, hyperoxia permanently triggered apoptotic cascades, evidenced by sustained transcript upregulation and increased histological apoptosis and cell loss across the cortex and hippocampus, while disrupting the hippocampal progenitor niche, suppressing key differentiation factors (Sox2, Tbr2, Prox1, Calb1) and altering mature NeuN expression. Likewise, markers for autophagy (Atg5/12, Beclin1), neurotrophins (BDNF, NGF, NT3), and plasticity markers (Nrp1, Sem3a) showed reduced expression. Proactive treatment with DEX (5 µg/kg) significantly reversed these detrimental patterns. First, DEX elicited a robust antioxidant response (Nrf2, SOD1, SOD3 induction). Second, DEX effectively suppressed hyperoxia-induced programmed cell death and tissue degeneration up to P14. Crucially, this dual protection sustained the neurogenic niche, safeguarding autophagy processes as well as neurotrophic and neuronal plasticity mediators, while showing excellent safety under normoxia. In conclusion, a single dose of DEX mitigates acute oxygen injury and exhibits beneficial, stage-specific effects within hippocampal neurogenic niches during the postnatal phase, highlighting its potential to preserve neurodevelopmental trajectories. Full article

Aims: Globally, cardiovascular disorders represent the foremost contributor to mortality, and elevated arterial pressure constitutes one of their principal risk determinants. Despite the availability of various treatments, optimal blood pressure control is rarely achieved. The present work was undertaken to assess the antihypertensive and vasorelaxant properties of benzaldehyde, a naturally occurring aromatic aldehyde whose role in the regulation of arterial pressure has, to our knowledge, not yet been documented. Materials and Methods: Antihypertensive activity was evaluated in normotensive Wistar rats and in animals rendered hypertensive by chronic administration of Nω-nitro-L-arginine methyl ester (L-NAME). Benzaldehyde was administered orally at doses of 20 and 40 mg/kg under both acute (6 h) and subacute (7-day) treatment protocols. Arterial pressure was recorded non-invasively by means of a tail-cuff plethysmography system. Vasorelaxant activity was examined in vitro using isolated rat aortic rings precontracted with either Epinephrine (EP, 10 μM) or potassium chloride (KCl, 80 mM). Endothelium-dependent and endothelium-independent components were dissected by pre-incubating the rings with selective pharmacological inhibitors. Additionally, the effects of benzaldehyde on both phasic and tonic contractions induced by extracellular Ca²⁺ were assessed in EP-precontracted rings in Ca²⁺-free Krebs solution. Key Findings: In hypertensive animals, benzaldehyde produced a dose-related decrease in both systolic and diastolic arterial pressure. It induced concentration-dependent vasorelaxation in both endothelium-intact and -denuded aortic rings. Relaxation was also observed in KCl-precontracted rings. Vasorelaxant responses were significantly attenuated by Indomethacin, Nifedipine, and 2-Aminoethoxydiphenyl borinate (2-APB). Significance: These findings demonstrate that benzaldehyde lowers blood pressure through both endothelium-dependent and -independent mechanisms. These include activation of the prostacyclin (PGI₂)/cAMP pathway, inhibition of L-type calcium channels, and blockade of store-operated calcium channels (SOCCs). Full article

Diabetic neuropathy (DN) is a multifactorial complication of diabetes mellitus driven by chronic hyperglycemia, insulin resistance, and disturbed metabolic homeostasis, leading to progressive injury of both the peripheral and central nervous systems. This study investigated whether L-serine supplementation could attenuate DN through dose-dependent metabolic and neuroprotective mechanisms in a high-fat diet (HFD) plus streptozotocin (STZ)-induced diabetic rat model. Male Wistar rats (n = 8 per group) were allocated to five groups: normal control (NC), diabetic control (DC), pioglitazone (PIO; 1.5 mg/kg/day), low-dose L-serine (S1; 200 mg/kg/day), and high-dose L-serine (S2; 400 mg/kg/day). After 60 days of oral gavage, behavioural testing, glucose and insulin profiling, HOMA-IR calculation, brain histopathology, nerve growth factor (NGF) immunohistochemistry, and LC–MS/MS-based proteomic analysis of cerebral tissue were performed. Diabetic rats exhibited marked hyperglycaemia (355.33 ± 4.72 mg/dL), hyperinsulinaemia, severe insulin resistance (HOMA-IR 16.8 ± 3.2; a 14-fold increase), impaired thermal nociception, motor dysfunction, and pronounced neuronal degeneration. L-serine supplementation significantly improved metabolic status: S1 reduced HOMA-IR by 77.4% and S2 by 87.5% relative to diabetic controls (p < 0.001). High-dose L-serine produced greater improvements in thermal sensitivity, motor coordination (rotarod latency 26.67 ± 1.52 s vs. 16.1 ± 0.85 s in DC; p < 0.05), and NGF expression (8.6-fold increase vs. DC). Histopathology confirmed attenuation of neuronal injury and gliosis in both treatment groups. Exploratory, group-level proteomic profiling identified dose-specific molecular signatures: S1 was predominantly associated with carbohydrate, lipid, and biosynthetic pathways, whereas S2 was associated with synaptic, neurotransmission-related, and proteostasis pathways. Within the constraints of an exploratory design—group-level pooled proteomics, analysis of cerebral rather than peripheral-nerve tissue, and only two doses—these findings indicate that L-serine attenuates the metabolic and behavioural features of experimental diabetic neuropathy and generates the testable hypothesis of dose-dependent neuro-metabolic remodelling. The proteomic signatures are hypothesis-generating and require orthogonal validation before any mechanistic or translational inference can be drawn. Full article

Bacterial cellulose (BC) is an emerging biopolymer for skin tissue regeneration; however, its functionalization with natural antimicrobial agents remains limited. This study reports the preclinical evaluation of a BC-based dressing for diabetic wounds. BC membranes were obtained from mango pulp agro-waste by Komagataeibacter xylinus cultivation (6.32 g/L) and functionalized with grapefruit seed oil (GSO) at three v/v ratios (1:100, 1:200 and 1:500). FTIR spectroscopy confirmed GSO incorporation into the BC matrix through physical interactions, with a dose-dependent loading. Antimicrobial activity of the BC/GSO dressings was screened against Staphylococcus aureus, Escherichia coli and Candida albicans by agar diffusion, showing dose-dependent inhibition zones. Following the minimum effective dose principle, the BC/GSO 1:500 (v/v) formulation was selected for comprehensive biocompatibility evaluation (cytotoxicity, mutagenicity, pyrogenicity and sensitization) and for in vivo wound-healing testing in a streptozotocin-induced diabetic Wistar rat model. Cell viability above 70% was achieved from membrane-extract dilution 1:100,000, while mutagenicity, pyrogenicity and sensitization assays confirmed the absence of adverse biological responses. In vivo, BC/GSO 1:500 (v/v) dressings supported wound closure comparable to nitrofurazone, with no clinical signs of infection. Overall, these results position BC/GSO dressings as a sustainable, biocompatible and antimicrobial candidate for early-stage diabetic wound regeneration and demonstrate the technical feasibility of valorizing mango pulp agro-waste into a high-value biomedical biopolymer. Full article

Hypothyroidism is associated with metabolic, neurobehavioral, and reproductive alterations that may involve neuroendocrine regulatory peptides. Spexin, a neuropeptide implicated in energy homeostasis, has recently attracted attention for its possible role in thyroid and reproductive axis regulation. Therefore, this study aimed to investigate the effects of spexin on neurobehavioral responses and the tissue-specific expression of irisin and KISS-1 in the cerebral cortex and testis under hypothyroid conditions. Thirty-two male Wistar albino rats were randomly divided into four groups: Control, Hypothyroid (methimazole, 0.03% in drinking water for 35 days), Hypothyroid + Spexin (methimazole plus spexin, 25 µg/kg, intraperitoneally), and Spexin (25 µg/kg, intraperitoneally). Behavioral assessments were performed using the Open Field Test and Forced Swim Test. Serum thyroid hormone levels were analyzed, and brain and testis tissues were evaluated immunohistochemically for irisin and KISS-1 expression. Hypothyroid rats showed increased thyroid-stimulating hormone levels, decreased thyroxine concentrations. Spexin administration significantly reduced TSH levels and increased T4 concentrations. Spexin treatment reduced thigmotaxis compared to controls. No significant differences were found among groups in overall locomotor activity, time spent in the central zone, or FST parameters. Immunohistochemical analyses demonstrated reduced irisin and KISS-1 expression in hypothyroid rats, which was restored following spexin treatment. In conclusion, spexin exerted TSH-suppressive and T4-enhancing effects in experimental hypothyroidism. Its effects on irisin and KISS-1 expression suggest potential involvement in neuroendocrine and reproductive axis regulation. Full article

Background/Objectives: Mesenchymal stem cells (MSCs), due to their regenerative and multipotent properties, have emerged as promising therapeutic agents in tissue repair and regeneration. These biological characteristics might contribute to optimized anastomotic healing and to a reduction in postoperative complications following digestive surgery. The present study aimed to evaluate whether intraperitoneal or perianastomotic administration of MSCs provides superior healing outcomes in colonic anastomoses in Wistar rats. Methods: MSCs were isolated from inguinal adipose tissue harvested from 2 Wistar rats. Thirty male Wistar rats were allocated to 3 groups: (i) the control group, with regular anastomosis, (ii) peri-anastomotic injection of MSCs, and (iii) intraperitoneal injection of MSCs. The animals were sacrificed on postoperative day 14. The evaluated outcomes included clinical evolution, adhesion index, histological characteristics, and tissue hydroxyproline content. Results: The incidence of anastomotic leakage and the mortality rate were 0%. Therefore, the present study primarily demonstrates changes in surrogate markers of healing, including inflammatory response, collagen deposition, adhesion formation, and hydroxyproline content. The adhesion index was similar in the groups receiving MSC administration (p = 0.05); however, intraperitoneal administration demonstrated superior outcomes when compared to standard anastomosis in reducing adhesion formation (p = 0.002). Histopathological analysis showed a decreased inflammatory process and an increased collagen deposition at the anastomotic site following MSC administration (p < 0.05). Moreover, tissue hydroxyproline levels were significantly increased after both perianastomotic (0.831 ± 0.02, p < 0.05) and intraperitoneal (0.54 ± 0.02, p < 0.05) MSC administration compared with the control group (0.251 ± 0.006). Conclusions: These results suggest that MSC administration may improve histological and biochemical markers associated with colonic anastomotic healing in a non-ischemic experimental model. The experimental model used is suitable for further studies aimed at determining the optimal indications, routes of administration, and adjunctive agents that may potentiate the effects of MSCs. Full article

Juvenile intestinal ischemia–reperfusion (JII/R) is a pediatric surgical emergency caused by mesenteric vessel occlusion and has a high mortality rate. Malrotation can cause intestinal ischemia in infants due to midgut volvulus. It affects not only the intestine itself but also other organs, such as cardiac tissue. Therefore, searching for more effective therapeutic solutions is an essential critical need. This directed our thoughts to evaluate the role of ambrisentan (AMB) in a rat model of induced JII/R by clamping the superior mesenteric artery. Forty juvenile male Wistar albino rats (3–4 weeks old) were randomly divided into four experimental groups: control (CON) group, JII/R group, and AMB-treated groups (30, 60 mg/kg) with JII/R. Induction of JII/R results in significant changes in cardiac enzymes, oxidative stress, inflammatory, and apoptotic parameters with high expression of endothelin receptor A (ERA). Also, histopathological changes revealed extensive mucosal damage, loss of intestinal villi, dysregulated and degenerated cardiac fibers with inflammatory cell infiltration, and tissue necrosis. In contrast, AMB administration significantly reduced the elevated levels of cardiac enzymes, malondialdehyde (MDA), nuclear factor kappa B (NF-κB), ERA, and caspase-3 expression. However, AMB treatment increased immune expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), Ki-67, and mammalian target of rapamycin (mTOR) and showed remarkable improvement in the histopathological changes. AMB could be considered as an adjuvant medical treatment for cases of JII/R. Full article

Liver fibrosis is a severe but common disease without an easy-to-access option for efficient treatment. Mesenchymal stem cells (MSCs) of different origins have been tested for antifibrotic effects in vitro, in vivo, and in clinical studies over the two last decades, although the comparative efficiency of different subtypes remains not fully understood, especially for long-term survival. In this study, we aimed to compare the long-time persistence of favorable effects in male Wistar rats with liver fibrosis treated using MSCs derived from white adipose tissue (AdMSCs) and bone marrow (BMSCs). Liver fibrosis was induced by carbon tetrachloride. We studied the survival rate; oxidative index, assessed via laser Doppler flowmetry; hepatic markers in blood plasma—albumin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase; the ratio of liver to body mass; histological parameters—the number of adipocytes, lymphocytes, siderophages, and Ki67⁺ cells; and the relative areas of connective tissue proper and reticular fibers. Extra mortality was only typical for fibrotic animals subjected to the sham treatment in the first two weeks. Up to Day 270 of this study, both MSC-treated groups showed barely any differences from animals undergoing the sham treatment in terms of the oxidative index and blood markers, although AdMSC-treated rats presented a more favorable histological pattern than BMSC-treated ones, considering the relative area of reticular fibers and the Ki67 cell count. This study suggests that AdMSC treatments may be more appropriate than BMSC treatments in animal liver fibrosis models, with the results showing better potential for liver tissue regeneration 9 months after treatment. Full article

Background: Oxidative stress contributes significantly to premature skin aging and inflammatory dermatological conditions. While plant-derived antioxidants have demonstrated considerable promise in topical applications, Bougainvillea glabra Choisy remains underexplored in standardized pharmaceutical dosage form development despite its documented phytochemical richness. Objective: This study aimed to develop, standardize, and characterize topical cold cream formulations incorporating B. glabra ethanolic leaf extract, with HPTLC-based quantification of marker compounds, validated antioxidant assessment, and preliminary dermal safety evaluation. Methods: The ethanolic leaf extract was prepared by maceration and characterized by preliminary phytochemical screening and HPTLC fingerprinting with quantitative densitometric analysis of quercetin and pinitol. Three cold cream formulations were developed at 10% (F1), 20% (F2), and 30% (w/w) (F3) extract loading. Formulations were evaluated for organoleptic properties, pH, homogeneity, spreadability, and viscosity. Antioxidant activity was assessed using a validated methanol extraction procedure followed by DPPH radical scavenging and potassium permanganate reduction assays. Ex vivo skin permeation was evaluated using Franz diffusion cells with freshly excised goat skin. Accelerated stability was conducted at 40 ± 2 °C/75 ± 5% RH for 90 days with HPTLC-based marker retention monitoring. Primary dermal safety was assessed in Wistar albino rats (n = 6) following OECD Test Guideline 404. Results: Quantitative HPTLC confirmed quercetin (4.82 ± 0.14 mg/g dry extract) and pinitol (2.31 ± 0.09 mg/g) as marker compounds, with linearly increasing content across F1–F3. All formulations demonstrated acceptable physicochemical properties (pH 5.7–5.9, viscosity 440,000–460,000 cP, spreadability 11.8 ± 0.3 cm·g/s). F3 exhibited the highest DPPH scavenging activity (56.68 ± 1.05%) with IC₅₀ of 1.3 ± 0.1% w/v, demonstrating a 3.2-fold improvement over F1. Extraction recovery from the cream matrix was 96.4–97.1%, validating the antioxidant data. Ex vivo quercetin permeation through goat skin reached 51.3 ± 2.8 μg/cm² at 24 h for F3, following Higuchi diffusion kinetics (R² > 0.99). No dermal irritation was observed (Primary Irritation Index = 0). Accelerated stability confirmed ≥98.3% retention of both marker compounds and antioxidant activity after 90 days. Conclusions: B. glabra leaf extract was successfully incorporated into a physicochemically stable, non-irritating cold cream with demonstrated dose-dependent antioxidant efficacy and cutaneous delivery capability. The study establishes preliminary dermal safety and in vitro antioxidant efficacy warranting further controlled clinical evaluation. Full article

Background/Objective: Highly palatable foods are pleasurable and motivational stimuli that activate the brain’s reward system and can induce overeating in the absence of physiological needs. This study investigated how different access patterns to a cafeteria diet influence food intake, body weight-related parameters, and metabolic and neurobehavioral outcomes. Methods: At postnatal day 31, forty male Wistar rats were assigned to a standard diet or a cafeteria diet with continuous, predictable intermittent, or unpredictable intermittent access. After 10 weeks, the open-field and sucrose-preference tests assessed exploratory and anxiety-like behaviors and reward-related responses, respectively. Body composition, serum biochemical parameters, neurotransmitter content, and mRNA and protein levels were analyzed in reward-related brain regions. Results: Intermittent access increased food intake on cafeteria days compared with continuous access, with unpredictable access yielding the highest intake. Continuous-access rats exhibited higher final body weight and fat accumulation than chow-fed Control rats. Despite similar body weight, both intermittent-access groups had higher visceral adiposity, obesity indices, and adverse metabolic outcomes than the Control group. All cafeteria-fed rats displayed anxiety-like behavior, and all groups preferred sucrose except the continuous-access group. Molecular analyses revealed region-specific differences in gene expression related to neuroplasticity, stress response, and epigenetic regulation that varied with access pattern and predictability. Conclusions: Our results suggest that, beyond diet composition, the pattern and predictability of food access are key determinants of feeding behavior. Intermittent access increases the motivational value of the cafeteria diet, promoting overeating and driving reward- and stress-related neuroadaptations with potential metabolic and mental health implications. Full article