Search Results (696)

Ischemic stroke is a serious disease that frequently occurs in the elderly and is characterized by a complex pathophysiology and a limited number of effective therapeutic agents. Salvianolic acid A (SAL-A) is a natural product derived from the rhizome of Salvia miltiorrhiza, which possesses diverse pharmacological activities. This study aims to investigate the effect and mechanisms of SAL-A in inhibiting ferroptosis to improve ischemic stroke. Brain injury, oxidative stress and ferroptosis-related analysis were performed to evaluate the effect of SAL-A on ischemic stroke in photochemical induction of stroke (PTS) in mice. Lipid peroxidation levels, antioxidant protein levels, tissue iron content, nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial morphology changes were detected to explore its mechanism. SAL-A significantly attenuated brain injury, reduced malondialdehyde (MDA) and long-chain acyl-CoA synthase 4 (ACSL4) levels. In addition, SAL-A also amplified the antioxidative properties of glutathione (GSH) when under glutathione peroxidase 4 (GPX4), and the reduction in ferrous ion levels. In vitro, brain microvascular endothelial cells (b.End.3) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) were used to investigate whether the anti-stroke mechanism of SAL-A is related to Nrf2. Following OGD/R, ML385 (Nrf2 inhibitor) prevents SAL-A from inhibiting oxidative stress, ferroptosis, and mitochondrial dysfunction in b.End.3 cells. In conclusion, SAL-A inhibits ferroptosis to ameliorate ischemic brain injury, and this effect is mediated through Nrf2. Full article

Fresh fruit are highly perishable commodities, facing significant postharvest losses primarily due to physiological deterioration and microbial spoilage. Conventional preservation methods often face limitations regarding safety, residue, and environmental impact. Because of its rapid decomposition and low-residue-impact characteristics, ozone has proven superior as an efficient and eco-friendly solution for preserving fruit quality after harvest. The maturation and aging processes of kiwifruit are closely linked to the involvement of reactive oxygen species (ROS) metabolism. This study aimed to investigate the effects of intermittent ozone treatment (21.4 mg/m³, applied for 0, 1, 3, or 5 h weekly) on ROS metabolism, the antioxidant defense system, and storage quality of kiwifruit during cold storage (0.0 ± 0.5 °C). The results showed ozone treatment slowed the decline in titratable acid (TA) content and fruit firmness, inhibited increases in total soluble solids (TSSs) and weight loss, and maintained the storage quality. Additionally, ozone treatment enhanced the activities of antioxidant-related enzymes. This includes superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX). Furthermore, it delayed the reduction in ascorbate (ASA), glutathione (GSH), total phenolic compounds, and flavonoid content, while also preventing the accumulation of ROS and the rise in malondialdehyde (MDA) levels. In summary, the results indicate that ozone treatment enhances the antioxidant capacity of kiwifruit by increasing the structural integrity of cell membranes, preserving the structural integrity of cell membranes, and effectively maintaining the storage quality of the fruit. Full article

This study aimed to investigate the efficacy of a composite coating composed of 150 mg/L ε-Poly-L-lysine (ε-PL) and 5 g/L chitosan (CTS) in extending the shelf life and maintaining the postharvest quality of fresh Tremella fuciformis. Freshly harvested T. fuciformis were treated by surface spraying, with distilled water serving as the control. The effects of the coating on storage quality, physicochemical properties, reactive oxygen species (ROS) metabolism, and membrane lipid metabolism were evaluated during storage at (25 ± 1) °C. The results showed that the ε-PL/CTS composite coating significantly retarded quality deterioration, as evidenced by reduced weight loss, maintained whiteness and color, and higher retention of soluble sugars, soluble solids, and soluble proteins. The coating also effectively limited water migration and loss. Mechanistically, the coated T. fuciformis exhibited enhanced antioxidant capacity, characterized by increased superoxide anion (O₂⁻) resistance capacity, higher activities of antioxidant enzymes (SOD, CAT, APX), and elevated levels of non-enzymatic antioxidants (AsA, GSH). This led to a significant reduction in malondialdehyde (MDA) accumulation, alongside improved DPPH radical scavenging activity and reducing power. Furthermore, the ε-PL/CTS coating preserved cell membrane integrity by inhibiting the activities of lipid-degrading enzymes (lipase, LOX, PLD), maintaining higher levels of key phospholipids (phosphatidylinositol and phosphatidylcholine), delaying phosphatidic acid accumulation, and consequently reducing cell membrane permeability. In conclusion, the ε-PL/CTS composite coating effectively extends the shelf life and maintains the quality of postharvest T. fuciformis by modulating ROS metabolism and preserving membrane lipid homeostasis. This study provides a theoretical basis and a practical approach for the quality control of fresh T. fuciformis. Full article

Soil salinization severely limits plant growth and productivity. Mulberry (Morus alba L.), an economically and ecologically important tree, is widely cultivated, yet its salt-tolerance mechanisms at the seedling stage remain insufficiently understood. This study investigated the physiological and biochemical responses of two-year-old mulberry (‘Tailai Sang’) seedlings subjected to six NaCl treatments (0, 50, 100, 150, 200, and 300 mmol L⁻¹) for 28 days. Results showed that growth parameters and photosynthetic gas exchange exhibited dose-dependent declines. The reduction in net photosynthetic rate (Pn) was attributed to both stomatal limitations (decreased stomatal conductance) and non-stomatal limitations, as evidenced by a significant decrease in the maximum quantum efficiency of photosystem II (Fv/Fm) under high salinity. To cope with osmotic stress, seedlings accumulated compatible solutes, including soluble sugars, proteins, and proline. Critically, mulberry seedlings demonstrated effective ion homeostasis by sequestering Na⁺ in the roots to maintain a high K⁺/Na⁺ ratio in leaves, a mechanism that was compromised above 150 mmol L⁻¹. Concurrently, indicators of oxidative stress—malondialdehyde (MDA) and H₂O₂—rose significantly with salinity, inducing the activities of antioxidant enzymes (SOD, CAT, APX, and GR), which peaked at 150 mmol L⁻¹ before declining under extreme stress. A biomass-based LC₅₀ of 179 mmol L⁻¹ NaCl was determined. These findings elucidate that mulberry salt tolerance is a coordinated process involving three key mechanisms: osmotic adjustment, selective ion distribution, and a robust antioxidant defense system. This study establishes an indicative tolerance threshold under controlled conditions and provides a physiological basis for further field-based evaluations of ‘Tailai Sang’ mulberry for cultivation on saline soils. Full article

Acute hepatopancreatic necrosis disease (AHPND), caused by the bacterium Vibrio parahaemolyticus, is a major threat to global shrimp aquaculture. In this study, we evaluated the therapeutic effects of phage therapy in Litopenaeus vannamei challenged with AHPND-causing Vibrio parahaemolyticus. Phage application at various concentrations significantly improved shrimp survival, with the 1 ppm group demonstrating the highest survival rate. Enzymatic assays revealed that phage-treated shrimp exhibited enhanced immune enzyme activities, including acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LZM). In addition, antioxidant defenses such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and total antioxidant capacity (T-AOC) significantly improved, accompanied by reduced malondialdehyde (MDA) levels. Serum biochemical analyses demonstrated marked improvements in lipid metabolism, particularly reductions in triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL), alongside higher levels of beneficial high-density lipoprotein (HDL). Transcriptomic analysis identified 2274 differentially expressed genes (DEGs), notably enriched in pathways involving fatty acid metabolism, peroxisome functions, lysosomes, and Toll-like receptor (TLR) signaling. Specifically, phage treatment upregulated immune and metabolic regulatory genes, including Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MYD88), interleukin-1β (IL-1β), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor (PPAR), indicating activation of innate immunity and antioxidant defense pathways. These findings suggest that phage therapy induces protective immunometabolic adaptations beyond its direct antibacterial effects, thereby providing an ecologically sustainable alternative to antibiotics for managing bacterial diseases in shrimp aquaculture. Full article

The functional role of MAPKK genes in potato (Solanum tuberosum L.) under high-temperature stress remains unexplored, despite their critical importance in stress signaling and yield protection. We characterized StMAPKK1, a novel group D MAPKK localized to plasma membrane/cytoplasm. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed cultivar-specific upregulation in potato (‘Atlantic’ and ‘Desiree’) leaves under heat stress (25 °C, 30 °C, and 35 °C). Transgenic lines overexpressing (OE) StMAPKK1 exhibited elevated antioxidant enzyme activity, including ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD), mitigating oxidative damage. Increased proline and chlorophyll accumulation and reduced oxidative stress markers, hydrogen peroxide (H₂O₂) and malondialdehyde (MDA), indicate improved cellular redox homeostasis. The upregulation of key antioxidant and heat stress-responsive genes (StAPX, StCAT1/2, StPOD12/47, StFeSOD2/3, StMnSOD, StCuZnSOD1/2, StHSFA3 and StHSP20/70/90) strengthened the enzymatic defense system, enhanced thermotolerance, and improved photosynthetic efficiency, with significant improvements in net photosynthetic rate (Pn), transpiration rate (E), and stomatal conductance (Gs) under heat stress (35 °C) in StMAPKK1-OE plants. Superior growth and biomass (plant height, plant and its root fresh and dry weights, and tuber yield) accumulation, confirming the positive role of StMAPKK1 in thermotolerance. Conversely, RNA interference (RNAi)-mediated suppression of StMAPKK1 led to a reduction in enzymatic activity, proline content, and chlorophyll levels, exacerbating oxidative stress. Downregulation of antioxidant-related genes impaired ROS scavenging capacity and declines in photosynthetic efficiency, growth, and biomass, accompanied by elevated H₂O₂ and MDA accumulation, highlighting the essential role of StMAPKK1 in heat stress adaptation. These findings highlight StMAPKK1’s potential as a key genetic target for breeding heat-tolerant potato varieties, offering a foundation for improving crop resilience in warming climates. Full article

Biochar has emerged as a promising soil amendment for mitigating heavy metal contamination in agricultural systems. This study investigates the effects of biochar on cadmium (Cd) and copper (Cu) uptake, plant growth, oxidative stress, and physiological responses in lettuce (Lactuca sativa L.) plants exposed to different metal concentrations. Results indicate that biochar significantly influenced Cd bioavailability, reducing its accumulation in plant tissues by up to 31.9% and alleviating oxidative stress, with malondialdehyde and proline levels decreasing by up to 51.0% and 60.2%, particularly at higher application rates (5%). Cd-exposed plants treated with biochar exhibited an improved fresh weight (+22.6%), lower malondialdehyde and proline levels, and enhanced the chlorophyll content (+14.9% to 24.1%) compared to untreated plants. The bioaccumulation factor for Cd decreased (up to 31.8%) while the immobilization index (II) increased, confirming the role of biochar in limiting Cd mobility in soil. In contrast, Cu uptake remained consistently low across all treatments, with a significant reduction observed only at higher contamination levels (up to −34.2%). Biochar contributed to Cu immobilization, reflected in increased II values, and enhanced the plant biomass and chlorophyll content under Cu exposure (+15.4% and up to +24.1%, respectively), suggesting a partial alleviation of Cu toxicity. These findings highlight biochar’s potential in heavy metal remediation, particularly for Cd, by reducing bioavailability and improving plant resilience. However, its role in Cu-contaminated soils is mainly through immobilization rather than uptake reduction. Full article

Dementia is marked by progressive cognitive decline linked to oxidative stress, neuroinflammation, and synaptic dysfunction. Curcumin, a natural compound from Curcuma longa, has shown promising neuroprotective effects. This systematic review analyzed 29 preclinical studies using rodent models of dementia induced by chemical, genetic, or dietary methods. The review focused on curcumin’s effects on oxidative stress, inflammation, and cognitive outcomes. All studies assessing malondialdehyde (MDA) reported significant reductions, indicating reduced oxidative stress. Superoxide dismutase (SOD) activity increased in all measured cases, while glutathione (GSH) levels rose in about one-third of studies. A literature search was comprehensively conducted using PubMed, Scopus, AMED, and LILACS databases through April 2024. Curcumin also demonstrated anti-inflammatory properties, with over 80% of studies showing reduced levels of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. Additionally, 40% of studies noted increases in anti-inflammatory markers like IL-4 and IGF-1. Cognitive performance improved in around 80% of studies, especially in spatial learning and memory. Some studies also reported behavioral improvements, including reduced anxiety and enhanced locomotion. Curcumin demonstrated potent antioxidative, anti-inflammatory, and cognitive-enhancing effects across diverse dementia models. Its ability to modulate multiple pathological pathways highlights its potential as a bioactive compound for mitigating cognitive decline associated with neurodegenerative diseases. However, variability in study design and curcumin formulations suggests the need for standardized protocols and further high-quality research to facilitate clinical translation. Full article

This study evaluated the effects of Yupingfeng polysaccharides (YPF-P) on production performance, immune response, and intestinal health in goslings. A total of 240 one-day-old healthy male goslings were randomly assigned to four groups, each with six replicates of ten goslings. The Control group (Control) was fed a basal diet, while the experimental groups received the basal diet supplemented with 200 mg/kg (YPFPI), 400 mg/kg (YPFPII), and 600 mg/kg (YPFPIII) of YPF-P. The results demonstrated that supplementation with 400 mg/kg of YPF-P significantly decreased the final body weight at 21 days and the feed conversion ratio (FCR) from days 1 to 14 (p < 0.05). Plasma activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were significantly elevated, while malondialdehyde (MDA) levels were reduced in the 400 and 600 mg/kg groups (p < 0.05). Both dosages significantly increased thymus and bursa of Fabricius indices, as well as plasma IL-1β concentration (p < 0.05), with IL-6 levels further elevated in the 600 mg/kg group (p < 0.05). Duodenal and ileal villus height and the villus height to crypt depth ratio were significantly improved in the 400 and 600 mg/kg groups (p < 0.05). In the cecum, acetate and isobutyrate concentrations were increased in the 400 and 600 mg/kg groups, while propionate concentration was significantly higher in the 600 mg/kg group (p < 0.05). The 600 mg/kg group also exhibited a significant increase in the relative abundance of beneficial bacteria such as Akkermansia and Alistipes, alongside a marked reduction in harmful pathogens, including Rickettsia (p < 0.05). In summary, dietary supplementation with YPF-P enhanced antioxidant capacity, immune response, and gut microbiota composition in goslings, with the most pronounced effects observed at 600 mg/kg. Full article

Cardiotoxicity related to anthracyclines and trastuzumab represents a significant clinical challenge in cancer therapy, often limiting treatment efficacy and patient survival. The underlying mechanisms of cardiotoxicity involve the activation of NLRP3 and the MyD88-dependent signaling pathway. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), such as inclisiran, are known for their lipid-lowering effects, but emerging data indicate that they may also exert pleiotropic benefits beyond cholesterol reduction. This study investigates whether inclisiran can mitigate the cardiotoxic effects of anthracyclines and trastuzumab through reduction of NLRP3 activation and MyD88 signaling, independently of its effects on dyslipidemia. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to subclinical concentrations of doxorubicin (1 µM) and trastuzumab in sequential therapy (200 nM), alone or in combination with inclisiran (100 nM) for 24 h. After the incubation period, we performed the following tests: determination of cardiomyocytes apoptosis, analysis of intracellular reactive oxygen species, lipid peroxidation products (including malondialdehyde and 4-hydroxynonenal), intracellular mitofusin-2 and Ca⁺⁺ levels. Troponin and BNP were quantified through selective ELISA methods. A confocal laser scanning microscope was used to study cardiomyocyte morphology and F-actin staining after treatments. Moreover, pro-inflammatory studies were also performed, including the intracellular expression of NLRP-3, MyD-88 and twelve cytokines/growth factors involved in cardiotoxicity (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IFN-γ, TNF-α, G-CSF, GM-CSF). Inclisiran co-incubated with doxorubicin and trastuzumab exerts significant cardioprotective effects, enhancing cell viability by 88.9% compared to only DOXO/TRA treated cells (p < 0.001 for all). Significant reduction of oxidative stress, and intracellular levels of NLRP-3, MyD88, IL-1α, IL-1β, IL-6, IL-12, IL17-α, TNF-α, G-CSF were seen in the inclisiran group vs. only DOXO/TRA (p < 0.001). For the first time, PCSK9i inclisiran has been shown to exert significant anti-inflammatory effects to reduce anthracycline-HER-2 blocking agent-mediated cardiotoxicity through NLRP-3 and Myd-88 related pathways. The overall conclusions of the study warrant further investigation of the use of PCSK9i in primary prevention of CTRCD in cancer patients, independently from dyslipidemia. Full article

This study investigated the effects of Trichoderma harzianum inoculation on the growth, physiological responses, and soil nutrient uptake of three turfgrass species cultivated on eco-concrete—Axonopus compressus (Sw.) Beauv., Cynodon dactylon (L.) Pers., and Zoysia sinica Hance. A 2 × 2 factorial design was used to evaluate plant growth, physiological responses, and soil metrics under cement stress, incorporating T. harzianum inoculation (inoculated vs. control) and substrate composition (eco-concrete vs. pastoral soil). Our results indicate that inoculation with Trichoderma harzianum significantly enhanced the growth potential of the three turfgrass species compared to uninoculated controls. Furthermore, under cement stress conditions in vegetated concrete, inoculation with T. harzianum significantly alleviated the inhibition of growth and development. More specifically, in the vegetated concrete habitat, inoculated plants exhibited significantly increased root length and surface area. This enhancement promoted the uptake of available nitrogen (AN), available phosphorus (AP), and available potassium (AK) from the soil. Concurrently, inoculated plants showed higher leaf epidermal cell density, stomatal width, soluble sugar content, and antioxidant enzyme activity (SOD, POD, CAT, and APX). Additionally, significant reductions were observed in root activity, relative conductivity, and malondialdehyde (MDA) and proline contents. In conclusion, T. harzianum inoculation promotes the growth of the three turfgrass species under cement stress, likely by enhancing root development, increasing osmoregulatory substance accumulation, and elevating antioxidant enzyme activities. Full article

Background/Objectives: Vancomycin-induced nephrotoxicity (VIN) remains a significant clinical challenge, with no effective nephroprotective agent currently established. This study aimed to evaluate the protective effects of the sodium–glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (DAPA) against VIN in a Wistar albino rat model. Methods: Rats were randomly assigned to four groups: control, VA (vancomycin), DAPA (dapagliflozin), and VA+DAPA. Renal function was assessed by measuring serum urea and creatinine. Oxidative stress markers [malondialdehyde (MDA), total oxidant status (TOS), and myeloperoxidase (MPO)], antioxidant enzyme activities [total antioxidant status (TAS), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD)], apoptotic mediators (Bax, Bcl-2, and caspase-3), and pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6)] were evaluated. Histopathological and immunohistochemical analyses of kidney tissues were also performed. Results: Administration of VA led to significant renal dysfunction, increased oxidative stress, heightened apoptotic activity, and notable histopathological damage. Co-administration of DAPA with VA significantly reduced serum urea and creatinine levels and decreased caspase-3 activity and was associated with a trend toward reduction in both MDA levels and TNF-α expression, as well as the amelioration of histopathological renal injury. However, reductions in IL-1β and IL-6 levels were not statistically significant. Overall, these findings indicate that DAPA exerts nephroprotective effects against VIN by modulating oxidative stress, inflammation, and apoptotic pathways. Conclusions: Dapagliflozin may serve as a potential protective agent against vancomycin-induced nephrotoxicity. Further long-term and large-scale clinical studies are warranted to validate these preclinical findings and explore their therapeutic implications. Full article

Climate fluctuations due to global warming significantly impact the wine grape industry. This study introduces the Standardized Temperature Adaptation Index (STAI), which is specifically designed to isolate temperature trends and quantify the effects of temperature fluctuations on low-temperature stress affecting Cabernet Sauvignon branches and yields in the wine grape production regions of Xinjiang. A low-temperature fluctuation experiment was conducted on Cabernet Sauvignon branches to simulate the temperature conditions and fluctuations experienced by wine grapes during the overwintering period. The treated branches then underwent recovery growth experiments, during which key physiological stress parameters were measured to assess the impact of temperature fluctuations on grape growth and development during overwintering. The results indicated that under identical low-temperature conditions, increased temperature fluctuations led to a 62% reduction in the budding rate of Cabernet Sauvignon branches, a 6% increase in relative conductivity, and elevated levels of proline, malondialdehyde, and soluble proteins. Additionally, the activities of superoxide dismutase, peroxidase, and catalase initially rose and then declined, indicating that temperature fluctuations intensified low-temperature stress. Data analysis from four wine grape production regions in Xinjiang between 2000 and 2020 revealed that temperature fluctuations corresponded with the peaks and troughs of yield fitting curves, demonstrating a negative correlation. As temperature fluctuations increased, yields decreased. The STAI introduced in this study is a straightforward, standardized measure that accurately reflects the effects of temperature fluctuations on grapes and is a valuable tool for future research on temperature variability and its impacts. Full article

Background: Quasipaa spinosa crude extract (QSce), a natural source rich in proteins such as parvalbumin (PV), has been traditionally used to promote physical recovery. However, its mechanisms in mitigating exercise-induced fatigue remain unclear. Methods: Using a murine treadmill exhaustion model, we evaluated the effects of QS-derived Parvalbumin (QsPV) (30 and 150 mg/kg/day) on endurance capacity, oxidative stress, tissue injury, and muscle function. Indicators measured included time to exhaustion, intracellular calcium levels, antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)], lipid peroxidation (malondialdehyde, MDA), injury markers [creatine kinase (CK), lactate dehydrogenase (LDH), cardiac troponin I (cTnI)], renal function (blood urea), and muscle force. Results: QsPV-150 significantly increased time to exhaustion by 34.6% compared to the exercise-only group (p < 0.01). It reduced MDA by 41.2% in skeletal muscle and increased SOD and GSH-Px levels by 35.4% and 28.1%, respectively. Serum CK, LDH, and cTnI were reduced by 39.5%, 31.7%, and 26.8%, respectively, indicating protection against muscle and cardiac injury. QsPV also decreased blood urea by 22.3% and improved renal histology, with reduced glomerular damage and tubular lesions. At the molecular level, QsPV restored calcium balance and downregulated calpain-1/2 and atrophy-related genes (MuRF-1, MAFbx-32). Muscle contractile force (GAS and SOL) improved by 12.2–20.3%. Conclusions: QsPV attenuates exercise-induced fatigue through multi-organ protection involving calcium buffering, oxidative stress reduction, and anti-atrophy effects. These findings support its potential as a natural recovery-enhancing supplement, pending further clinical and pharmacokinetic studies. Full article

: Negative energy balance (NEB) in dairy cows induces excessive lipolysis, leading to elevated levels of β-hydroxybutyric acid (BHBA), which, when accumulated, can cause liver damage. Rutin (RT), a natural flavonoid with antioxidant and anti-inflammatory properties, has demonstrated potential hepatoprotective effects; however, its ability to mitigate BHBA-induced hepatocellular injury in calves remains unclear. This study first assessed the impact of various BHBA concentrations on oxidative stress in calf hepatocytes, then explored the protective effects and underlying mechanisms of RT, and finally employed untargeted metabolomics to further elucidate RT’s mode of action. The results showed that exposure to 1.2 mM BHBA significantly increased malondialdehyde (MDA), nitric oxide (NO) contents, and reactive oxygen species (ROS) levels, while markedly decreasing glutathione (GSH) content and catalase (CAT) activity compared with the blank control. Notably, pretreatment with 100 μg/mL RT resulted in the greatest increase in GSH contents (180%) compared to BHBA treatment alone, while 150 μg/mL RT led to the most pronounced reduction in MDA contents (220%). Furthermore, BHBA treatment significantly upregulated the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone dehydrogenase 1 (NQO1), and heme oxygenase-1 (HO-1) at both the mRNA and protein levels. These alterations were effectively reversed by pretreatment with 100 μg/mL RT. Non-targeted metabolomics identified 1525 metabolites in total. Based on OPLS-DA, metabolites with a variable importance in projection (VIP) > 1 and p < 0.05 were considered significantly altered. Compared with the blank control, BHBA treatment upregulated 47 metabolites—including 8-hydroxy-2′-deoxyguanosine, 3-hydroxyisovaleric acid, and N-palmitoyl-sphingosine—and downregulated 58 metabolites, such as betaine, linolenic acid, and arachidonic acid. In contrast, RT pretreatment upregulated 207 metabolites relative to the BHBA treatment, including linolenic acid, taurocholic acid, and 4-hydroxybenzoic acid, and downregulated 126 metabolites, including 3-hydroxyisovaleric acid, 8-hydroxy-2′-deoxyguanosine, and pyruvaldehyde. Pathway enrichment analysis indicated that RT alleviated BHBA-induced hepatocyte injury primarily by modulating the fatty acid degradation pathway. In summary, RT mitigated BHBA-induced oxidative stress in calf hepatocytes by regulating the Keap1/Nrf2 signaling pathway and further exerted protective effects through metabolic reprogramming. Full article