Potential Liver Research Articles

JuA alleviates liver ischemia-reperfusion injury by activating AKT/NRF2/HO-1 pathways

Liver ischemia-reperfusion (I/R) injury is a detrimental complication of organ transplantation, shock, and sepsis. However, the available drugs to mitigate I/R injury remain limited. Jujuboside A (JuA) is renowned for its antioxidant, anti-inflammatory, and anti-apoptotic properties; nevertheless, its potential in liver I/R injury remains unknown. Thus, this study aimed to explore the role and underlying mechanisms of JuA in liver I/R injury. Mouse models of I/R and AML12 cell models of hypoxia/reoxygenation (H/R) were constructed. Haematoxylin and eosin staining, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) detection, and cell viability analysis were used to assess liver injury. To evaluate oxidative stress, inflammation, apoptosis, and mitochondrial damage, immunofluorescence staining, transmission electron microscopy analysis, enzyme-linked immunosorbent assay, and flow cytometry were conducted. Moreover, molecular docking techniques and western blot were employed to identify downstream target molecules and pathways affected by JuA. The results showed that JuA pretreatment effectively attenuated liver necrosis and ALT and AST level elevations induced by I/R while enhancing AML12 cell viability following H/R. Furthermore, JuA pretreatment suppressed oxidative stress triggered by I/R and H/R, thereby inhibiting the level of pro-inflammatory factors and NLRP3 inflammasome activation. Notably, JuA pretreatment alleviated mitochondrial damage and apoptosis. Mechanistically, JuA pretreatment resulted in the activation of the AKT/NRF2/HO-1 signalling pathways, whereas MK2206, the inhibitor of AKT, partially reversed the hepatoprotective effects of JuA during liver I/R. Collectively, our findings illustrated that JuA mitigated oxidative stress, inflammation, apoptosis, and mitochondrial damage by facilitating the AKT/NRF2/HO-1 signalling pathway, thereby alleviating liver I/R injury.

LXR Agonist T0901317's Hepatic Impact Overrules Its Atheroprotective Action in Macrophages, Driving Early Atherogenesis in Chow-Diet-Fed Male Apolipoprotein E Knockout Mice.

Preclinical studies regarding the potential of liver X receptor (LXR) agonists to inhibit macrophage foam cell formation and the development of atherosclerotic lesions are generally executed in mice fed with Western-type diets enriched in cholesterol and fat. Here, we investigated whether LXR agonism remains anti-atherogenic under dietary conditions with a low basal hepatic lipogenesis rate. Hereto, atherosclerosis-susceptible male apolipoprotein E knockout mice were fed a low-fat diet with or without 10 mg/kg/day LXR agonist T0901317 supplementation for 8 weeks. Importantly, T0901317 significantly stimulated atherosclerosis susceptibility, despite an associated increase in the macrophage gene expression levels of cholesterol efflux transporters ABCA1 and ABCG1. The pro-atherogenic effect of T0901317 coincided with exacerbated hypercholesterolemia, hypertriglyceridemia, and a significant rise in hepatic triglyceride stores and macrophage numbers. Furthermore, T0901317-treated mice exhibited elevated plasma MCP-1 levels and monocytosis. In conclusion, these findings highlight that the pro-atherogenic hepatic effects of LXR agonism are dominant over the anti-atherogenic effects in macrophages in determining the overall atherosclerosis outcome under low-fat diet feeding conditions. A low-fat diet experimental setting, as compared to the commonly used high-fat-diet-based preclinical setup, thus appears more sensitive in uncovering the potential relevance of the off-target liver effects of novel anti-atherogenic therapeutic approaches that target macrophage LXR.

Haematological, biochemical, enzymological changes and mitochondrial dysfunction of liver in freshwater climbing perch Anabas testudineus during their acute and chronic exposure to sodium fluoride

Anthropogenic activities are increasing fluoride concentration in watercourses. The present study focuses on the sublethal toxicity of sodium fluoride during sub-chronic and chronic time periods in the freshwater fish Anabas testudineus. The 96-hour LC50 value for fluoride was found to be 616.50 mg/L. Excessive mucous production and hyper excitability, followed by loss of balance, were seen in fish under acute fluoride exposure. Significant reduction in yield and specific growth rate of fish were assessed at 15, 30 and 45-days exposure intervals. Different bio-indicators like Hepatosomatic-index, Gonadosomatic-index and fecundity were reduced significantly in fish exposed to 10% (61.6 mg/L) and 20% (123.2 mg/L) of 96 h of LC50 values of fluoride in comparison to control. Toxicant concentrations directly correlated with parameter lowering. Fluoride exposure increased plasma glucose, creatinine, AST, and ALT and reduced total RBC, haemoglobin content, Hct (%), plasma protein, and cholesterol. Moreover, fluoride exposure significantly reduces the mitochondrial membrane potential in liver. This may result in metabolic depression, haematological, biochemical, and enzymological stress. The in-silico structural analysis predicts that fluoride may impede cytochrome c oxidase of the electron transport system, hence inhibiting mitochondrial functionality. These findings collectively highlight the urgent need for stringent regulation and monitoring of fluoride levels in freshwater ecosystems, as the subchronic and chronic effects observed in A. testudineus may have broader implications for aquatic ecosystems.

Regulatory Effects and Mechanisms of L-Theanine on Neurotransmitters via Liver-Brain Axis Under a High Protein Diet.

Excessive protein intake causes liver and brain damage and neurotransmitter disorders, thereby inducing cognitive dysfunction. L-theanine can regulate the neurotransmitter content and show great potential in liver and brain protection. However, it remains unclear whether l-theanine effectively regulates neurotransmitter content under high-protein diet. A 40-day feeding experiment was performed in Sprague Dawley rats to investigate the regulatory effects and mechanisms of l-theanine on neurotransmitters via liver-brain axis in high-protein diets. The results showed that a 30% protein diet increased the liver and brain neurotransmitter content while maintaining the normal structure of liver and the hippocampal CA1 of brain and improving the autonomous behavior of rats. In contrast, 40% and 50% protein diets decreased the content of neurotransmitters, affected autonomous behavior, destroyed the hippocampal CA1 of brain structure, increased hepatic inflammatory infiltration, lipid degeneration, and hepatocyte eosinophilic change in liver, increased liver AST, ALT, MDA, CRP, and blood ammonia level, and decreased liver SOD and CAT level. However, l-theanine improved liver and brain neurotransmitter content, autonomous behavior, liver and hippocampal brain structure, and liver biochemical indicators in 40% and 50% protein diets. To explore how LTA can eliminate the adverse effects of a high-protein diet, we analyzed different metabolites and proteomes and using western blotting for validate quantitatively. We found that l-theanine regulates the activity of PF4 and G protein subunit alpha i2, increases the content of brain-derived neurotrophic factor and dopamine under a 20% protein diet. In addition, l-theanine can activate the adenylate cyclase-protein kinase A pathway through the protein alpha/beta-hydrolase domain protein 12 to regulate the content of neurotransmitters under a 40% protein diet, thereby exerting a neuroprotective effect.

Evaluation of Hepatoprotective and Nephroprotective Effect of Α- Pinene on Wistar Albino Rat

Introduction: Hepato-renal toxicity is a devastating, non-communicable disease. Because of a lack of information on low-cost management to combat the disease, this study postulates the ameliorative effect of selected phytoconstituents against toxicity. Aim and Objective: The current study reveals an active phytoconstituent, α- Pinene, that has the ability to combat the degenerative effects of CCl4. Methodology: Carbon tetrachloride (CCl4) is an organic xenobiotic molecule as well as the most potent hepatotoxic agent used (1200 mg/kg body weight; i.p.) to induce hepato-renal toxicity in experimental rats. To determine in vivo hepato-renal toxicity, three different doses (0.05 ml/kg body weight, 0.1 ml/kg body weight, and 0.15 ml/kg body weight; intraperitoneally) were chosen. Vitamin C at the dose of 250 mg/kg/p.o. was used as a standard, due to its maximum ameliorative activity against oxidative damage in CCl4-induced hepato-renal toxicity in rats. For 7 days, the animals were pre-treated with α-pinene and Vitamin C. CCl4 was charged only on the 7th day. Result and Conclusion: The related biochemical tests were studied. CCl4 intoxication reduces mitochondrial membrane potential in liver and kidney cells, which accelerates excessive intracellular ROS production, but α-pinene pretreatment successfully restores it in both liver and kidney cells. Pretreatment with α-pinene and vitamin C for 7 days increased intracellular ameliorative capability in hepatic and renal cells significantly (p 0.01). In conclusion, α-pinene is capable of restoring antioxidant status by quenching intracellular ROS. As a result, α-pinene has the potential to provide hepatoprotective and nephroprotective effects against CCl4-induced toxicity in rats.

On the Utilization of Dietary Glycerol in Carnivorous Fish—Part II: Insights Into Lipid Metabolism of Rainbow Trout (Oncorhynchus mykiss) and European Seabass (Dicentrarchus labrax)

Glycerol is the by-product of biodiesel production and its utilisation in fish feed has recently gained relevance. As an important metabolic intermediate and structural component of triacylglycerol (TAG), it is still unclear whether its supplementation affects lipid utilisation and/or deposition in different tissues. Accordingly, a set of studies was aimed to evaluate how increasing levels of dietary glycerol (0, 2.5 and 5%) affect lipid synthesis in the liver, muscle and adipose tissue. After a growth trial with rainbow trout (8 weeks) and European seabass (6 weeks) fish were sampled at 6 and 24 h to assess mRNA levels of lipid metabolism-related enzymes. The remaining fish were subjected to a metabolic trial consisting of a 6-day residence in deuterated water (2H2O) for metabolic flux calculations. This study stands as the second part of a broader experiment that also aimed at evaluating the carbohydrate metabolism (Viegas et al., 2022). Dietary supplementation at 5% glycerol significantly increased plasma TAG levels in both species and liver TAG levels in seabass, with no repercussions on the perivisceral fat index. Despite responding as expected in a postprandial setting, only fas and Δ6-fad in trout and Δ6-fad in seabass responded significantly by increasing with the dietary supplementation of glycerol. In trout, the observed differences in the regulation of these enzymes were not reflected in the de novo lipogenic fluxes. The fractional synthetic rates (FSR) were overall low in all tissues with an average of 0.04, 0.02 and 0.01% d–1, for liver, muscle and perivisceral fat, respectively. In seabass on the other hand, and despite increased mRNA levels in Δ6-fad, the overall lipid profile in the liver muscle and perivisceral fat was higher in MUFA at the expense of lower PUFA. Moreover, glycerol supplementation altered the lipogenic capacity of seabass with hepatic fractional synthetic rates for TAG-bound FA increasing with increasing glycerol levels (0.32 ± 0.18, 0.57 ± 0.18, and 0.82 ± 0.24 for 0%, 2.5% and 5% glycerol supplementation, respectively). The findings of the present study suggest that supplementation up to 2.5% of glycerol did not severely impact the lipid metabolism nor increased lipogenic potential in liver, muscle and perivisceral fat accumulation.

Arsenic Biotransformation: It is a complex process

Arsenic Biotransformation: It is a complex process

Arsenic and Protein Expression: It might help to know the mechanism of As toxicity

Arsenic and Protein Expression: It might help to know the mechanism of As toxicity

Abstract 978: Magnolol induces apoptosis and inhibits metastasis via suppression of NF-κB activation in human bladder cancer

Abstract Magnolol is a phenolic compound extracted from magnolia officinalis, and known as a common Chinese medicinal material used in the treatment of strokes, colds, etc. Magnolol has also recognized as an anti-inflammation agent which can downregulate several inflammation signals transduction. Several reports suggested that magnolol may also have anti-tumor potential in liver and colon cancer. Nevertheless, the regulatory mechanism of magnolol on apoptosis and NF-κB signaling in human bladder cancer has not been elucidated. Thus, the purpose of the study was to investigate the mechanism and therapeutic efficacy on bladder cancer. First of all, we used MTT assay to investigate the cytotoxicity induction after magnolol treatment in bladder cancer. Then, we used NF-κB translocation assay to evaluate whether the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was decreased after magnolol treatment. We also detected the apoptosis induction ability of magnolol on extrinsic/intrinsic apoptosis pathway. This study demonstrated that magnolol significantly triggered the accumulation at the sub-G1 phase, the loss of mitochondrial membrane potential, and the activation of cleaved caspase-3, -8 and -9. Further verify the effect of magnolol on the expression of anti-apoptotic related proteins, we performed Western blotting. Magnolol inhibited migration and invasion ability of bladder cancer were investigated by wound healing and invasion assay. Then, we performed Western blotting to detect whether magnolol may inhibit NF-κB-mediated downstream signaling that involving in anti-apoptosis and metastasis such as MCL-1 and MMP9 protein expression. Moreover, the reduction of Cyclin D1 protein expression was used to evaluate the inhibition of cell proliferation by magnolol. In sum, our result demonstrated that magnolol induced extrinsic and intrinsic apoptosis mechanism and inhibit invasion/migration ability of bladder cancer was associated with the inactivation of NF-κB. Citation Format: Sin-Rong Lee, Zhao-Lin Tan, Yuan Chang, I-Tsang Chiang, Fei-Ting Hsu. Magnolol induces apoptosis and inhibits metastasis via suppression of NF-κB activation in human bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 978.

Selenium (Se) as well as mercury (Hg) may influence the methylation and toxicity of inorganic arsenic, but further research is needed with combination of Inorg-arsenic, Se, and Hg

Selenium (Se) as well as mercury (Hg) may influence the methylation and toxicity of inorganic arsenic, but further research is needed with combination of Inorg-arsenic, Se, and Hg

Does and duration of exposure time dependent regulation of proteins in the urinary bladder of hamsters exposed to sodium arsenite

Does and duration of exposure time dependent regulation of proteins in the urinary bladder of hamsters exposed to sodium arsenite

Regulation of transgelin and GST-pi proteins in the tissues of hamsters exposed to sodium arsenite

Regulation of transgelin and GST-pi proteins in the tissues of hamsters exposed to sodium arsenite

Probiotic Bifidobacterium Lactis Combined with Lactobacillus Plantarum Effectively Reduced Weight and Intestinal Microbiota

Probiotics intake can ameliorate body weight and fatty liver development. The fruit and vegetable also performed antiinflammation effects. The fermented vegetable solid drink (FVSD) was combined fruit and vegetable with probiotics and further examining the anti-obesity efficacy in this study. The FVSD promote lipolytic activity effect was examined on OP9 cells and the anti-inflammation effect was performed via Q-PCR analysis on C2BBe1. To investigate the weight management potential and gut microbiota influence. The obese subjects were recruited, and then performed anthropometric measurement and next-generation sequencing (NGS) after FVSD intervention. In the results, the lipolytic activity effects were significantly increased and the LPS induced inflammation response was significantly reversed by FVSD co-treatment. After FVSD administration, obese subjects were significantly ameliorated body weight, body fat weight, and body fat at 4 weeks. And the waist-to-hip ratio was improved at 8 weeks. Both aspartate aminotransferase (AST), alanine aminotransferase (ALT) were significantly improved with anti-fatty liver potential. The NGS analysis suggested FVSD intervention could increase Christensenellaceae and Parabacteroides abundance of subjects’ gut microbiota. In conclusion, FVSD performed a great anti-obese effect in vitro and in vivo.

Evaluation of Anti-hypertrophic Potential of Enicostemma littorale Blume on Isoproterenol Induced Cardiac Hypertrophy.

The main objective of this study is to evaluate the anti-hypertrophic potential of the aqueous extract of Enicostemma littorale (E. littorale) against isoproterenol induced cardiac hypertrophic rat models (male albino Wistar rats) through biochemical investigations. Aqueous extract of E. littorale known for various beneficial properties was administered (100mg/kg, 12days, oral) to isoproterenol (ISO) induced cardiac hypertrophic rats (low ISO-60mg/kg, 12days and high ISO-100mg/kg, 12days, subcutaneous) and were compared with group that was treated with the reference drug, Losartan (10mgkg, administered for 12days, oral). The anti-hypertrophic effect of E. littorale was evaluated by analysing the morphometric indices of the heart, ECG tracings, changes in blood biochemical parameters viz., serum glucose, serum total protein, serum albumin, lipid profile, cardiac specific enzymes (SGOT, SGPT and LDH) and histopathological examination of the heart tissue. The results fundamentally revealed that the plant extract efficiently ameliorated cardiac hypertrophy induced by ISO injected in experimental rats. The outcomes of biochemical investigations of this study highlighted the association between the hypertrophic β-adrenergic receptor signalling (β-AR) and the 5' AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) axis in the metabolism of cardiac fibrosis and hypertrophy. This β-AR/AMPK-PGC1α signalling stem can serve as a key target in ameliorating cardiac hypertrophy through focus on its principal regulators. To add, we also propose that the glycoside, swertiamarin present in this plant with the reported anti-fibrotic potential in liver can be further isolated and evaluated for its anti-hypertrophic potential to treat cardiac hypertrophy.

Fractional uptake of circulating tumor cells into liver-lung compartments during curative resection of periampullary cancer.

Circulating tumor cells (CTCs) are able to predict outcome in patients with breast, colon and prostate cancer and appear to be promising biomarkers of pancreatic carcinoma. The aim of the present study was to demonstrate a statistically significant portal-arterial difference of CTCs during curative resection of periampullary cancer. A commercially available instrument (IsofluxR) was used to quantify blood content of CTC in 10 patients with periampullary cancer according to preoperative diagnostics. Portal and arterial blood samples (~8 ml each) were simultaneously collected intra-operatively following surgical dissection prior to division of the pancreas for tumor removal. Quantitative CTC analyses were performed according to standardized protocols for immune-magnetic enrichment of CTC. Flow cytometry was applied for qualitative evaluations of various CTC markers in 7 patients. There was a statistically significant difference in the number of CTCs collected in the portal blood [58±14 cells per 100 ml; mean ± standard error (SE)] vs. arterial blood [24±7 cells per 100 ml (SE), P<0.025]. A fractional uptake of ≥40% across liver and lung compartments of assumed malignant CTC was estimated to correspond to the appearance of ~410 tumor cells per minute during pancreatic resections based on estimated hepatic blood flow, measured tumor cell mass and tumor cell proliferation activity. Complications in the collection of portal blood were not observed. A significant uptake across liver or lung compartments of potentially malignant tumor CTCs from periampullary carcinoma may represent a model to capture, define and characterize cell clones with metastatic potential in liver and lung tissues following surgical resection.

Shaping the future of liver surgery: Implementation of experimental insights into liver regeneration.

SummaryBackgroundWhile liver surgery has become a safe and feasible operation technique, the incidence of postoperative liver dysfunction still remains a central problem. Approximately 10% of patients undergoing liver resection were shown to develop liver dysfunction, which is associated with an increased risk of morbidity and mortality. Yet, to date there is no effective treatment option for postoperative liver dysfunction available. The development of postoperative liver dysfunction was linked to a disruption in the liver’s potential to regenerate. Thus, it is importance to elucidate the underlying mechanisms of liver regeneration and to find potential therapeutic targets for the treatment of patients with postoperative liver dysfunction.MethodsA review of the literature was carried out.ResultsWe report on potential future interventions for improvement of liver regeneration after surgical resection. Moreover, we evaluate the benefits and drawbacks of hepatic progenitor cell therapy and hematopoietic stem cell therapy. However, the most significant improvement seems to come from molecular targets. Indeed, von Willebrand factor and its pharmacologic manipulation are among the most promising therapeutic targets to date. Furthermore, using the example of platelet-based therapy, we stress the potentially adverse effects of treatments for postoperative liver dysfunction.ConclusionThe present review reports on the newest advances in the field of regenerative science, but also underlines the need for more research in the field of postoperative liver regeneration, especially in regard to translational studies.

Integration of liver and blood micronucleus and Pig-a gene mutation endpoints into rat 28-day repeat-treatment studies: Proof-of-principle with diethylnitrosamine

Regulatory guidance documents stress the value of assessing multiple tissues and the most appropriate endpoints when evaluating chemicals for in vivo genotoxic potential. However, conducting several independent studies to consider multiple endpoints and/or tissue compartments is resource intensive. Furthermore, conventional approaches for scoring genotoxicity endpoints are slow, tedious, and less objective than what would be considered ideal. In an effort to address these issues with current practices, we attempted to i) employ flow cytometry-based methods to score liver micronuclei, blood micronuclei, and blood Pig-a gene mutation, and ii) integrate the endpoints into a common general toxicology study design—the rat 28-day repeat dose study. A proof-of-principle experiment was performed with 6-week old male Crl:CD(SD) rats exposed to diethylnitrosamine (DEN) for 28 consecutive days. One day later blood was collected for micronucleated reticulocyte (MN-RET) and Pig-a mutation assays, and liver tissue was obtained for micronucleated hepatocyte (MNHEP) scoring. MN-RET frequencies were not affected by DEN exposure, and mean Pig-a mutant cell frequencies were only slightly elevated. On the other hand, % MNHEP showed marked, dose-related increases (2.2, 7.2, and 9.1 mean fold-increase for 5, 10, 15 mg DEN/kg/day, respectively). Concurrent with MNHEP analyses, assessments of Ki-67-positive events and the proportion of 8n nuclei provided evidence for treatment-related changes to hepatocyte proliferation. Collectively, these results reinforce the importance of evaluating chemicals’ genotoxic potential in liver in addition to hematopoietic cells, and suggest that several automated measurements can be successfully integrated into repeat-dose studies for higher efficiencies and better utilization of fewer animals.

Effects of Dietary Soapwort Extract Supplementation on Laying Performance, Blood Biochemical Parameters, Fatty Acid Profile of Breast Meat and Antioxidative Potential of Liver and Heart Tissues in Cold Stressed Laying Japanese Quail

Effects of Dietary Soapwort Extract Supplementation on Laying Performance, Blood Biochemical Parameters, Fatty Acid Profile of Breast Meat and Antioxidative Potential of Liver and Heart Tissues in Cold Stressed Laying Japanese Quail

Impact of Peripheral Ketolytic Deficiency on Hepatic Ketogenesis and Gluconeogenesis during the Transition to Birth

Preservation of bioenergetic homeostasis during the transition from the carbohydrate-laden fetal diet to the high fat, low carbohydrate neonatal diet requires inductions of hepatic fatty acid oxidation, gluconeogenesis, and ketogenesis. Mice with loss-of-function mutation in the extrahepatic mitochondrial enzyme CoA transferase (succinyl-CoA:3-oxoacid CoA transferase, SCOT, encoded by nuclear Oxct1) cannot terminally oxidize ketone bodies and develop lethal hyperketonemic hypoglycemia within 48 h of birth. Here we use this model to demonstrate that loss of ketone body oxidation, an exclusively extrahepatic process, disrupts hepatic intermediary metabolic homeostasis after high fat mother's milk is ingested. Livers of SCOT-knock-out (SCOT-KO) neonates induce the expression of the genes encoding peroxisome proliferator-activated receptor γ co-activator-1a (PGC-1α), phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase, and glucose-6-phosphatase, and the neonate's pools of gluconeogenic alanine and lactate are each diminished by 50%. NMR-based quantitative fate mapping of (13)C-labeled substrates revealed that livers of SCOT-KO newborn mice synthesize glucose from exogenously administered pyruvate. However, the contribution of exogenous pyruvate to the tricarboxylic acid cycle as acetyl-CoA is increased in SCOT-KO livers and is associated with diminished terminal oxidation of fatty acids. After mother's milk provokes hyperketonemia, livers of SCOT-KO mice diminish de novo hepatic β-hydroxybutyrate synthesis by 90%. Disruption of β-hydroxybutyrate production increases hepatic NAD(+)/NADH ratios 3-fold, oxidizing redox potential in liver but not skeletal muscle. Together, these results indicate that peripheral ketone body oxidation prevents hypoglycemia and supports hepatic metabolic homeostasis, which is critical for the maintenance of glycemia during the adaptation to birth.

Diosgenin prevents hepatic oxidative stress, lipid peroxidation and molecular alterations in chronic renal failure rats

Aim: Chronic renal failure (CRF) is one of the major contributors of cardiovascular pathological events and CRF associated uremic condition in rats elevates liver oxidative stress. The aim of the present study was to evaluate the preventive potential of diosgenin on antioxidant system and molecular protection potential in liver of CRF rats. Materials and Methods: CRF in rats was induced by feeding rats with diet containing 0.75% adenine for 5 weeks. Diosgenin was given orally at a dose of 40 mg/kg body weight (bw) of animal each and every day. The activities of antioxidant enzymes and lipid peroxidation level were determined by biochemical assays. Fourier transform infrared spectroscopy (FTIR) was employed to illustrate the molecular protection potential of diosgenin. Results: This study has shown adenine containing diet induced CRF in rats elevates liver oxidative stress by suppressing the activity of enzymatic antioxidant system, increased lipid peroxidation, and macromolecular structural alterations. In this study, treatment of diosgenin 40 mg/kg bw of rat significantly restores the enzymatic antioxidant system and reduces the lipid peroxidation level. Moreover, based on the FTIR study, we confirmed that diosgenin administration significantly protected the macromolecular changes including, the protein structural damage that occurred in liver. Conclusion: This study has proved the hepato protective action of diosgenin through antioxidant and molecular protection effect in CRF condition.