Aug 2026· Experimental and Clinical Gastroenterology· pp. 175-194· 0 citations· 11 references
TL;DR
Chronic aluminum exposure was associated with an increase in Zip1 gene expression in the liver, whereas continuous administration of the oxidized pectin-oxymethyluracil complex normalized its expression to control levels, contributing to a reduction in AST and LDH activity.
Abstract
Objective - The aim of the study was to experimentally assess the preventive effect of a complex of oxidized pectin and oxymethyluracil on chronic aluminum-induced hepatotoxicity in rats based on molecular and biochemical parameters. Materials and Methods. The experiment was conducted on 56 outbred female rats that received oral administration of aluminum hydroxide at a dose of 15 mg/kg and a chelate complex of oxidized pectin with oxymethyluracil (50 mg/kg) under various preventive and post-exposure regimens for 3-4 months. The expression of metallothionein genes (Mt1, Mt2, Mt3) and zinc transporter genes (Zip1, Zip8) in liver tissue was determined by real-time PCR using specific primers, SYBR Green intercalating dye, and the reference gene Gapdh. Serum activity of AST, ALT, ALP, and LDH was measured; statistical analysis was performed using IBM SPSS Statistics 21 software with one-way ANOVA at a critical significance level of p=0,05. Results. In our study, chronic aluminum exposure was associated with an increase in Zip1 gene expression in the liver, whereas continuous administration of the oxidized pectin-oxymethyluracil complex normalized its expression to control levels. The expression of Zip8 and metallothionein genes (Mt1a, Mt2a, Mt3a) did not change significantly among the experimental groups. At the biochemical level, this complex, when used preventively, contributed to a reduction in AST and LDH activity. Conclusion. The oxidized pectin-oxymethyluracil complex in a rat model of chronic aluminum hydroxide exposure normalizes Zip1 gene expression and reduces AST and LDH activity. Further studies using an expanded set of morphological and molecular markers are required to clarify the organoprotective mechanisms of the complex.
Abstract Antioxidants play a crucial role in the treatment of liver pathologies, given that oxidative stress is involved in the pathogenesis of many hepatic diseases. This study aimed to investigate the pharmacodynamic and pharmacokinetic properties of the antioxidant 2,6-diisobornyl-4-methylphenol (IBP) in a rat model of carbon tetrachloride (CCl4)-induced liver injury. The introduction of IBP resulted in a 1.4- to 2-fold decrease in serum hepatic enzyme levels, a 25% and 18% rise in glutathione peroxidase and superoxide dismutase concentrations, respectively, and a 14% reduction in hepatic catalase activity compared with the negative control. Treated animals exhibited a 45% reduction in malondialdehyde (a marker of oxidative stress) and an 18% decrease in interleukin-6 levels relative to controls. The compound mitigated CCl4-induced liver damage and promoted restoration of liver function. Liver pathology affected the plasma exposure of IBP after a single administration, but pharmacokinetics normalized following repeated dosing. Bioavailability was 60% after a single dose and increased to 119% after multiple administrations. IBP demonstrated significant hepatoprotective effects in CCl4-induced liver injury, mitigating lipid peroxidation, inflammation, and necrosis. The initial reduction in systemic exposure following a single dose in pathological conditions may be attributed to impaired absorption and elevated metabolic consumption due to oxidative stress.
E. A. Yanovskaya, G. Frelikh, A. Lakeev et al.· Free radical research· 0 citations
Background Of all the chemicals released into the environment, nonylphenol (NPL) has been shown to boost oxidative disturbance in the body by interfering in the stability of cells\' pro- and antioxidant pathways. A natural substance high in polyphenolic chemicals with antioxidant properties is rutin. This study\'s objective was to investigate effectiveness of rutin in alleviating oxidative stress and infertility problems induced by NPL in male albino rats.
Methods a total of 40 male rats were separated into 5 groups (8 rats each), aged 6 weeks and 150-170±1.77 gm b.wt and treated orally, 3 times weekly for 60 days. GI: control vehicle (distilled water); GII administrated (50 mg DMSO/kg b. wt.); GIII received (25 mg rutin/kg b. wt.); GIV: intoxicated with (50 mg NPL/kg b. wt.); GV was co-treated with rutin (as in GIII) along with NPL (as in GIV). To measure the quality of the semen, samples were taken for viability, motility, immotile and concentration of sperms assessment. Also, within testicular tissues, superoxide dismutase (SOD), catalase (CAT) activities, and level of malondialdehyde (MDA) were analyzed. Histopathological and immunohistochemical methods were used to examine morphological alterations in the testis. RT-PCR was applied to quantify the expression level of aromatase and steroidogenic acute regulatory (StAR) genes.
Results Oxidative stress is exhibited in NPL-treatment as indicated by decline in sperm quality and activities of CAT, SOD and increasing MDA lipid peroxidation biomarker concentration. Meanwhile, no changes observed in aromatase and steroidogenic acute regulatory (StAR) genes expression. Additionally, histopathological changes and increased tumor necrosis factor –α, and caspase 3 expression level caused by NPL in compared with control group. Rutin improved the deleterious effects of NPL. Rutin alone increased aromatase, decreased StAR genes expression.
Conclusion rutin serves as an effective protective agent against NPL-associated infertility and reproductive failure by modulating steroidogenic, inflammatory, and apoptotic pathways. This research establishes a foundation for using natural polyphenols to counteract the reproductive risks posed by environmental contaminants.
Doaa A Madkour, Mohamed M. Ahmed, A. Elkirdasy et al.· Alexandria Journal of Veteri...· 0 citations
ABSTRACT Introduction: Toxic hepatitis is characterized by enhanced oxidative stress and disruption of antioxidant defense mechanisms in the liver mitochondria. In this study, we investigated the effects of polyphenolic extracts (Helmar-1 and Helmar-2) obtained from Helichrysum maracandicum on mitochondrial antioxidant systems in rats with experimentally induced toxic hepatitis. Methods: Experimental toxic hepatitis was established in rats through intraperitoneal administration of carbon tetrachloride (CCl₄) diluted in olive oil (50%, 1 mL/kg), administered twice weekly over a two-week period. Liver injury was verified by elevated plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The animals were subsequently treated with Helmar-1 and Helmar-2 extracts at a dose of 20 mg/kg per day for 10 consecutive days. The activities of key antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), malondialdehyde (MDA) content, and mitochondrial respiration and oxidative phosphorylation parameters (V₂, V₃, V₄, RCR, and ADP/O ratio) were assessed in liver mitochondria. Results: Treatment with both Helmar-1 and Helmar-2 extracts resulted in a significant enhancement of antioxidant enzyme activities, a marked reduction in MDA levels, and substantial improvement in mitochondrial respiration and oxidative phosphorylation parameters compared to untreated toxic hepatitis groups. Conclusion: Overall, these results confirm that Helichrysum maracandicum polyphenol extracts improve mitochondrial respiration, oxidative phosphorylation efficiency, antioxidant defense, and membrane stability in toxic hepatitis.
S. Ahmedova, M. Asrarov, S. Mirzakulov et al.· Drug Target Insights· 0 citations
Background:
Methotrexate (MTX) is one of the most frequently used chemotherapeutic and immunosuppressive agents; however, its clinical use is limited to hepatotoxicity and other organ toxicities associated with oxidative stress and inflammatory responses.
Aim:
The current study was conducted to evaluate the potential protective effect of the ethanolic extract of Rosmarinus officinalis against MTX-induced hepatorenal injury in Wistar rats.
Methods:
Hepatorenal toxicity was induced in Wistar rats via a single intraperitoneal administration of MTX (20 mg/kg). Rosemary extract was orally administered at doses of 100 and 200 mg/kg body weight. Liver function biomarkers (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), renal function parameters (urea and creatinine), and hematological indices were determined alongside oxidative stress markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione, and Malondialdehyde) and levels of tumor necrosis factor-alpha (TNF-α). Hem atoxylin and eosin staining and immunohistochemical profiling were used for histopathological evaluation.
Results:
MTX caused a significant increase in liver enzymes, oxidative markers, and TNF-α while lowering antioxidant defenses. Histopathological examination revealed hepatocyte degeneration, vascular congestion, and inflammatory infiltration. Treatment with R. officinalis extract alleviated these changes in a dose-dependent manner, resulting in improved biochemical parameters and reduced tissue injury.
Conclusion:
Rosmarinus officinalis extract may exert protective effects against MTX-induced hepatorenal injury through antioxidant and anti-inflammatory mechanisms. However, further studies are required to confirm these effects and validate their therapeutic potential.
Lana Muhammed, Nadia Salih· Open Veterinary Journal· 0 citations
Introduction: Cyclophosphamide, as a chemotherapeutic drug, causes induction of oxidative stress and disruption in the testis structure and function. In this study, the effect of selenium as a strong antioxidant on the testicular tissue of male mice after treatment with cyclophosphamide was evaluated.
Methods: For this experimental study, 32 adult male NMRI mice were divided into four groups of eight: control, cyclophosphamide (100 mg/kg, administered once weekly), selenium (1 mg/kg daily for 35 days), and a combination of cyclophosphamide and selenium. Following the 35-day treatment period, the mice were dissected; the left testis was utilized to measure malondialdehyde (MDA) levels and total antioxidant capacity (TAC), while the right testis, after undergoing fixation, tissue processing, sectioning, and hematoxylin-eosin staining, was employed for stereological analyses. Data were analyzed using SPSS software, applying one-way ANOVA followed by Tukey’s post-hoc test, with statistical significance set at p<0.05.
Results: In the cyclophosphamide group compared to control, a significant decrease was observed in mean total testis volume, seminiferous tubules volume (p<0.001), interstitial tissue volume (p<0.01), as well as in the length, diameter, and height of the germinal epithelium. basement membrane thickness, number of spermatogenic, Sertoli and Leydig cells, spermatogenesis indices, Johnsen score, and TAC level of testicular tissue (p<0.001), while the MDA level significantly increased (p<0.001). In the cyclophosphamide plus selenium group, these changes were compensated at the control level.
Conclusion: The results showed that cyclophosphamide induces oxidative stress, causes disruption in the structure and function of the testis. While selenium reduced these damages and improved important histological and oxidative stress parameters to levels similar to the control group, suggesting a protective role against cyclophosphamide-induced testicular damage.
M. Mehranjani, Zahra Safari, Sepideh Ahmadi· Journal of Shahid Sadoughi U...· 0 citations
Overall, chrysin demonstrates potent protective potential against PFOA-induced liver injury and may serve as a promising therapeutic candidate for environmental toxin-associated hepatotoxicity.
A. B. Awolesi, Moses C. Antiya, S. A. Praise· Innovative Medicines & O...· 0 citations