Background: Patulin (PAT) is a mycotoxin commonly detected in spoiled fruits and fruit-derived products. PAT exposure can induce liver injury through oxidative stress, inflammatory responses, and mitochondrial dysfunction. Aim: This study aimed to evaluate whether selenium-enriched Tibetan kefir grain-fermented goji juice (SFGJ) could serve as a protective dietary intervention against PAT-induced liver injury. Methodology: Se-enriched Tibetan kefir grains were prepared under optimized conditions, including 2% inoculum, selenium addition at 2 h, and 36 h cultivation. The optimized grains were then used to ferment goji juice at 28 °C for 36 h. Selenium content, total phenolic content, in vitro antioxidant activity, serum biochemical markers, oxidative stress indices, inflammatory cytokines, liver histopathology, and gut microbiota were evaluated. Result: The optimized Se-enriched Tibetan kefir grains contained 1356.60 ± 23.75 μg g[-1] total selenium, of which 86.81 ± 0.89% was organic selenium. SFGJ showed increased total phenolic content (271.18 ± 1.20 mg GAE per 100 mL) and DPPH radical scavenging activity (80.07 ± 1.56%). In PAT-exposed mice, SFGJ reduced liver histopathological damage and decreased serum ALT, AST, and LDH levels. SFGJ also improved antioxidant status, as indicated by increased SOD and GSH-Px, and attenuated inflammatory responses by increasing IL-10 and decreasing IL-6, IL-1β, and TNF-α. 16S rRNA gene sequencing showed that PAT reduced microbial richness, whereas SFGJ treatment restored ASV richness to a level close to that of the blank control. SFGJ was also associated with increased relative abundance of Ligilactobacillus and Akkermansia and decreased relative abundance of Desulfovibrio. Conclusion: These findings suggest that SFGJ may be a promising fermented functional food for reducing PAT-associated liver injury. Its protective effect may be related to improved redox balance, reduced inflammation, and gut microbiota modulation. Further studies are needed to identify key bioactive metabolites, verify intestinal barrier function, and evaluate dose-response relationships.

Calcium stearyl lactylate (CSL) is a widely used food emulsifier, particularly in pasta products. In this study, we investigated the potential toxicological effects of CSL exposure on organ health and gut microbiota in mice. Over a 12-week period, mice were administered CSL at 50, 500, and 5000 mg/kg·bw. Our study found that CSL exposure induced liver and colon inflammation, significantly elevating hepatic injury markers (ALT and AST). In parallel, key intestinal functional markers (CXCL-1, CXCL-2, IL-1β, TNF-α, ZO-1, and Occludin) were markedly altered, indicating compromised gut barrier integrity. 16S rRNA sequencing revealed that CSL administration disrupted gut microbial diversity, characterized by decreased beneficial bacteria (e.g., Bifidobacterium and Lactobacillus) and increased potentially harmful genera, including Anaerotruncus, Desulfovibrio, and Helicobacter. These findings indicate that long-term CSL intake can induce hepatointestinal damage and provoke significant dysbiosis of the gut microbiome.

Mancozeb (MNZ), a widely used dithiocarbamate fungicide, has been associated with oxidative stress-mediated organ toxicity in nontarget species. The present study investigated the potential protective effects of N-acetylcysteine (NAC) against MNZ-induced hepatotoxicity and nephrotoxicity in rats. Thirty-two adult male Wistar rats were randomly assigned to four groups: Control, NAC (200 mg/kg, i.p.), MNZ (500 mg/kg, p.o.), and MNZ + NAC for 28 days. Serum biochemical parameters, tissue oxidative status, inflammatory cytokine levels, apoptosis-related gene expression, and histopathological alterations were evaluated in liver and kidney tissues. MNZ administration significantly elevated serum ALT, AST, GGT, bilirubin, creatinine, and urea levels compared with controls (p < 0.05). In both liver and kidney tissues, MNZ caused a significant increase in the oxidative stress index (OSI) by elevating total oxidant status (TOS) and reducing total antioxidant status (TAS) (p < 0.001). Pro-inflammatory cytokines (IL-1β, IL-6) and the mRNA expression of TNF-α, iNOS, COX-2, Bax, and caspase-3 were significantly upregulated, whereas Bcl-2 expression and the Bcl-2/Bax ratio were reduced. Histopathological evaluation confirmed substantial structural deterioration in both organs. NAC co-administration significantly attenuated biochemical abnormalities, restored redox balance, modulated inflammatory and apoptotic gene expression, and markedly improved tissue architecture. These findings indicate that MNZ induces hepatorenal injury through oxidative stress-associated inflammatory and apoptotic processes, and that NAC confers significant protective effects by restoring cellular redox homeostasis and limiting downstream tissue damage.

Hysterothylacium thalassini third-stage larvae (L3), commonly found in marine fish, are known to induce liver injury, oxidative stress, and immune disturbances when transmitted to mammalian hosts. This study investigated the pathological effects of purified crude extracts derived from fresh, heat-treated, and frozen L3 larvae on liver function, oxidative status, and immune responses in a murine model. Thirty Saurida tumbil fish were examined for L3 larvae, which were processed under three conditions: fresh (24 ± 2 °C for 60 min), heat-treated (100 °C for 60 min), and frozen (-20 °C for 24 h). Twenty male C57BL/6 mice were randomly allocated into four groups and inoculated with larval extracts at a 14-day interval. Mice exposed to fresh larval extracts exhibited significant weight loss, elevated liver enzymes (ALT, AST, ALP), hyperglycemia, and reduced total protein levels, alongside severe hepatic damage characterized by necrosis and inflammatory infiltration. Antioxidant enzyme activities (CAT and SOD) were markedly decreased, whereas oxidative stress markers (NO and H₂O₂) were increased. Additionally, there was significant upregulation of iNOS, TNF-α, and IL-10 gene expression, accompanied by elevated iNOS, IL-10, and IgE protein levels, indicating strong inflammatory and Th2-type immune responses. In contrast, extracts from heat-treated and frozen larvae resulted in attenuated pathological effects, including improved liver function, reduced oxidative stress, and moderated immune responses. These findings demonstrate that untreated L3 larval extracts exert pronounced hepatotoxic and immunomodulatory effects, while thermal and freezing treatments significantly reduce their pathogenicity and support immune homeostasis, highlighting potential strategies to mitigate parasite-induced host damage.

Characterization of toxin-induced mouse models of regressive liver disease, focusing on the detecting of a suitable therapeutic window during fibrosis and portal hypertension (PH) regression. C57BL/6JRj mice were studied when exposed to thioacetamide (TAA) or carbon tetrachloride (CCl4) for 8 or 12 weeks (8w/12w) and after one/two (+R1/+R2) week(s) of TAA/CCl4-free regression. Healthy controls received NaCl or olive oil (OO). Primary readouts included liver fibrosis (collagen proportionate area, CPA), portal pressure (PP), serum transaminases and hepatic fibrosis-related gene expression. The diseased models (8wTAA/12wTAA/8wCCl4/12wCCl4) showed significant fibrosis (CPA: 3.03/3.87/8.53/16.90%; vs. NaCl/OO: 0.87/1.15%) and PH (PP: 6.8/7.7/8.5/10.0 mmHg; vs. NaCl/OO: 5.5/5.1 mmHg). CPA significantly regressed in 8wTAA+R1 (2.60%; p = 0.01) and 12wCCl4+R1 (10.9%; p = 0.01), but not in 12wTAA+R1/8wCCl4+R1. CPA regression was significant in all +R2-groups (p < 0.001) but not in 8wCCl4+R2 (p = 0.30). Significant PP regression was found at 8wCCl4+R1 (5.8 mmHg; p = 0.004) and 12wCCl4+R1 (8.4 mmHg; p = 0.01), but not in the 8w/12w TAA models. All +R2-groups showed significant PP regression: 8wTAA+R2 (6.0 mmHg; p ≤ 0.001), 12wTAA+R2 (6.0 mmHg), 8wCCl4+R2 (6.0 mmHg, p = 0.004) and 12wCCl4+R2 (7.9 mmHg, p = 0.008). Serum AST/ALT levels at +R1/+R2 returned to levels of healthy controls. Hepatic Col1a1 and Timp1 gene expression peaked in 12w-groups and showed a gradual decrease at +R1/+R2: Col1a1 (12wTAA+R1/+R2: -14%/-29%, p = 0.002; 12wCCl4+R1/R2: -28%/-23%, p = 0.05) and Timp1 (12wTAA+R1/+R2: -41%/-61%, p ≤ 0.001; 12wCCl4+R1/R2: -43%/-40%, p ≤ 0.001). While liver disease regressed in all models/timepoints, both liver fibrosis (CPA) and PP remained increased in the 12wCCl4+R1/R2 settings - qualifying this model as suitable for pre-clinical testing of therapeutic strategies aimed at promoting liver fibrosis and PH regression.

Monocrotaline (MCT), a plant-derived pyrrolizidine alkaloid, is well known for its hepatotoxic effects. However, full elucidation of the mechanisms underlying MCT-induced hepatotoxicity, as well as the development of reliable biomarkers for early detection and monitoring, requires an integrated evaluation of biochemical, molecular, and histopathological data. This study aims to evaluate the hepatotoxic effects of MCT using biochemical, molecular, and histopathological data. Thirty male BALB/c mice were randomly assigned to three groups: control, acute toxicity, and subacute toxicity. The control group received saline, the acute group received a single dose of 120 mg/kg MCT, and the subacute group received the same dose administered three times at 5-day intervals. Blood and liver tissues were collected for biochemical and oxidative stress analysis. Apoptotic markers were evaluated at the protein and gene expression levels using ELISA, qPCR, and PCR array. Histopathological examination was performed to assess structural liver alterations. MCT significantly increased hepatic enzyme levels including ALT, GGT, and TBIL, while AST levels showed a nonsignificant numerical increase and were associated with disrupted lipid and protein metabolism, evidenced by increased TCHO and decreased TP. Oxidative stress markers (TOS, OSI) increased in the acute group with reduced TAS, whereas TAS increased in the subacute group, indicating temporal modulation of antioxidant defenses. Bax and caspase-3 were upregulated, and Bcl-2 was downregulated at the protein level. qPCR corroborated these findings at the transcriptional level, although without statistical significance. Histopathological analysis revealed extensive hepatic injury, particularly in the acute toxicity group. The findings indicate that MCT induces liver injury via enzymatic dysregulation, oxidative stress, and apoptosis and highlight the need for further research to identify reliable biomarkers for the early detection and monitoring of MCT-induced hepatotoxicity.