Rat Liver Tissue Research Articles

Hepatoprotective potentials of Usnea longissima Ach. and Xanthoparmelia somloensis (Gyelnik) Hale extracts in ethanol-induced liver injury

In our study, the antioxidant and anti-inflammatory effects of different lichen applications were investigated in rats using an experimental ethanol toxicity model. 48 rats were used in the study and they were divided into 6 groups with 8 rats in each group. These groups were: control, ethanol (2 g/kg), ethanol + Usnea longissima Ach. (200 mg/kg), ethanol + Usnea longissima Ach. (400 mg/kg), ethanol + Xanthoparmelia somloensis (Gyelnik) Hale (100 mg/kg) and ethanol + Xanthoparmelia somloensis (Gyelnik) Hale (200 mg/kg). The experimental work continued for 21 days. Lichen extracts and ethanol were administered by gavage to rats divided into groups. According to the experimental protocol, the experimental animals were sacrificed and their liver tissues were isolated. Biochemical parameters in serum, histological examinations, oxidative stress and inflammation parameters both at biochemical and molecular level in liver tissues were performed. Oxidative stress and inflammatory response were increased in the liver tissue of rats treated with ethanol for 21 days, and liver functions were impaired. It was found that U. longissima and X. somloensis extracts showed good antioxidant activity and conferred protective effects against ethanol-induced oxidative stress and inflammation. This could be attributed to the presence of secondary metabolites in the extract, which act as natural antioxidants and could be responsible for increasing the defence mechanisms against free radical production induced by ethanol administration.

Evaluation of the Efficacy of Ozone Therapy on Liver Tissue in the Treatment of Sepsis in Rats with Cecal Perforation.

Background and Objectives: Sepsis and its related complications are associated with high morbidity and mortality, often leading to liver damage. Ozone, a molecule with anti-inflammatory and antioxidant properties, may offer protective effects. This study aimed to evaluate the therapeutic and protective impact of ozone on liver injury in a rat model of sepsis induced by cecal ligation and perforation (CLP). Material and Methods: A total of 36 rats were randomly divided into five groups: control (Group C), ozone (Group O), cecal ligation and perforation (Group CLP), ozone + cecal ligation and perforation (Group O+CLP), and cecal ligation and perforation + ozone (Group CLP+O). In the ozone groups, 4 mL of ozone (20 µ/mL) was injected intraperitoneally. Biochemical and histopathological parameters were evaluated in liver tissue samples obtained at the end of 24 h. Results: Polymorphonuclear leukocyte and monocyte infiltration and the total injury score were significantly reduced in the ozone-treated groups compared to the CLP group (p < 0.001). Tumor necrosis factor and interleukin 10 levels in the rat liver tissue were significantly reduced in the O+CLP and CLP+O groups compared to the CLP group, with the O+CLP group showing a more substantial decrease than the CLP+O group (p < 0.001). Thiobarbituric acid reactive substances and glutathione s-transferase levels were significantly lower in the ozone-treated groups compared to the CLP group (p < 0.001). Catalase activity was significantly elevated in the O+CLP group compared to the CLP group (p < 0.001). Serum aspartate transaminase, alanine transaminase, gamma-glutamyl transferase, and total bilirubin were significantly increased in the CLP group and decreased in the ozone-treated groups (p < 0.001, p < 0.001, p = 0.01, p < 0.001 respectively). Conclusions: Administering ozone to rats one hour before the CLP significantly mitigated liver damage, showing a more pronounced effect compared to administering ozone one hour after CLP. The results indicate that ozone could serve a protective function in managing sepsis-induced liver damage.

Protective effect of propolis in protecting against radiation-induced oxidative stress in the liver as a distant organ

Stresses caused by ionizing radiation can also damage tissues and organs through the circulatory system. In this study, we aimed to determine the radioprotective effect of propolis, a natural and powerful antioxidant product, against oxidative liver damage caused by cranial irradiation. Thirty-two male albino Sprague–Dawley rats, divided into four groups, were designed as sham group, irradiation (IR) group, propolis plus IR, control group of propolis. Biochemical parameters were measured in liver tissue of rats. While Total enzymatic superoxide scavenging activity (TSSA) and non-enzymatic superoxide scavenging activity (NSSA), glutathione peroxidase (GSH-Px) activities of all groups were statistically significantly higher than rats receiving only-irradiation, Glutathione-S-transferase (GST) activity in the IR group was significantly lower than in the sham control group and IR + propolis group. Superoxide dismutase (SOD) activity in the IR group was found to be significantly higher than both the sham control group and the propolis control group, but lower than the IR + propolis group. Malondialdehyde level and xanthine oxidase activity were higher in the IR group than in the other groups. Compared to the sham control group, in the group treated with propolis, a significant elevation in antioxidant parameters, specifically TSSA, NSSA, SOD, and GST activities, was noted, with corresponding increases of 32.3%, 23.2%, 47.6%, and 22.6%, respectively. Our findings show that propolis can be a radioprotective agent against ionized radiation damage by increasing antioxidant activity and reducing oxidant stress in liver tissue.

Saffron (Crocus Sativus Linnaeus) based protection against Aflatoxin B1 induced organ damage in rats

Saffron is well-known for its anti-apoptotic, anti-inflammatory, and antioxidant properties. Saffron's nutritional and medicinal properties support its numerous uses as a flavouring and herbal remedy. This study investigated the protective efficacy of saffron administration against aflatoxin B1 (AFB1)-induced toxicity in adult male Wistar albino rats during an experimental period of 21 days. Aflatoxin B1 (AFB1) is a common mycotoxin of soils and foodstuffs. Thirty-two rats were divided into four groups (Control group, AFB1 group, Saffron group, and AFB1+ Saffron group), and their body weights were measured on days 1, 7, 14, and 21. Blood samples were collected on the 21st day for haematological and biochemical studies (testosterone, kidney and liver function tests, and oxidative stress markers). Tissue samples from testes, liver, and kidney were subjected to histological examinations. The results depicted a significant decrease in the body weights after 7, 14, and 21 days of Saffron, AFB1, and AFB1+ Saffron treatments in comparison to control. Haematological investigations showed that basophils, platelets, monocytes, lymphocytes, and eosinophils greatly increased compared to the control group, whereas neutrophils and eosinophils dramatically decreased. There was a significant rise in the serum levels of uric acid, creatinine, aspartate transaminase, alkaline phosphatase, nitric oxide, and malondialdehyde. Contrarily, testosterone levels notably reduced in AFB1-administered rats as compared to controls. AFB1 group exhibited several histological modifications in testes, liver, and kidney tissues. Oxidative stress biomarkers, testosterone, kidney and liver functions, and haematological parameters of the AFB1+ Saffron group remained similar to the control group. Kidney and liver tissues of Saffron-treated rats also displayed normal structure similar to the control group, which confirmed its protective efficacy against AFB1-induced toxicity. Saffron's bioactive components and antioxidant and pharmacological properties might have contributed to its promising anti-AFB1-toxicity potential.

The Influence of Experimental Chronic Antenatal and Acute Postnatal Hypoxia on the Morphological State of the Liver Stromal Component

BACKGROUND: At present, the asymptomatic course of liver pathology in early childhood remains an urgent problem. AIMS: The objective of the study was the detection of morphological features of the stromal component of the liver of rats, which were at different stages of postnatal ontogenesis and were exposed to chronic antenatal and acute postnatal hypoxia (APH). MATERIALS AND METHODS: The study material was rat liver tissue of the control group, the APH group, and the chronic antenatal hypoxia (CAH) group. RESULTS: From day 1 to day 35, CAH leads to an increase and growth of the stromal component in the liver of offsprings due to the development of sclerotic changes caused by activation of collagen formation with a predominance of mature collagen Type I over immature collagen Type III on day 1 and day 14 of the experiment and predominance of collagen Type III over collagen Type I on day 35 of the experiment, increasing the expression of fibronectin. Starting from day 14, APH leads to the development of sclerotic changes in this organ which increase to day 35, less pronounced compared to the detected sclerotic changes in CAH, and manifest in increased expression of fibronectin, activation of collagen formation with a predominance of collagen Type I over collagen Type III on days 14 and 35 of the experiment. CONCLUSION: CAH from day 1 and APH from day 14 of postnatal life lead to the development of sclerotic changes in the liver of offsprings, which are more pronounced in cases of simulation of CAH and increase with age.

Investigation of the effects of apilarnil and imatinib use on liver and kidney tissues in rats via PI3K/AKT/mTOR and JAK2/STAT3 pathways

Investigation of the effects of apilarnil and imatinib use on liver and kidney tissues in rats via PI3K/AKT/mTOR and JAK2/STAT3 pathways

Assessment of the toxic influence of locally formulated pesticides on hepatic and renal biomarkers in male Wistar rats.

There is growing concern of the potential damage to vital organs after long term exposure to locally formulated pesticides in rural area of Nigeria. This study was designed to assessed the effects of the individual chemical compound and their combination on the kidney and liver of rats' model. Fifty-four rats divided into six groups and three sub-groups were exposed to 25, 50 and 75% dose of each of the pesticide's LD50 for 4h at 3days interval in an inhalation chamber for 28days. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TOT_BIL), creatinine and urea assay showed significant increase at the aforementioned doses in comparison to the control group. The red blood cell counts, hematocrit and hemoglobin concentrations were significantly altered in the rats administered varying doses of the pesticides when compared with the control. Similar result was obtained for the differential white blood cell counts. Histopathological examinations of the liver tissue of rats showed infiltrated sinusoids, traces of karypyknosis, vacuolar degeneration and microvesicular steatosis while that of the renal tissue showed glomeruli atrophy leading to widened Bowman's spaces as well as few shrunken glomeruli and varied level of degenerative tubular changes to tubular necrosis. This study established that individual pesticides and their mixture is toxic to the liver and kidney, as evidenced by the elevated markers of renal and liver functions and distortion of the structure of both organs as revealed by their photomicrographs. Therefore, it is a matter of public health significance to regularly monitor pesticide residues in foods and humans in order to assess the food safety risk and population exposure to pesticides.

Ameliorative effects of Monascus-fermented hawthorn extract on a high-fat diet-induced rat model of non-alcoholic fatty liver disease

ObjectiveThe aim of this study was to elucidate the effects of fermented hawthorn extract on high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in rats, and explore the possible underlying mechanisms. MethodsA total of 42 male adult Sprague-Dawley rats were randomly divided into five groups: normal control group (given a normal feed diet and distilled water by gavage), NAFLD model (given HFD and distilled water by gavage), low-, medium-, and high-dose fermented hawthorn extract treatment groups (given HFD and different doses of fermented hawthorn extract by gavage). After 12 weeks of gavage administration, changes in body weight, liver/body weight ratio, serum liver enzymes, as well as triglyceride (TG) content and oxidative stress levels in rat liver tissueswere detected. Histological evaluation was performed to observe the degree of fat accumulation (steatosis). qRT-PCR and western blotting were performed to detect the mRNA and protein expression of cytochrome P4502E1 (CYP2E1, a key enzyme associated with lipid peroxidation), and lipogenic factors (sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS)) in rat liver tissues. ResultsFermented hawthorn extract significantly reduced the body weight, decreased the levels of liver enzymes, improved hepatic steatosis, and exhibited obvious antioxidant effects. Fermented hawthorn extract also significantly down-regulated the mRNA and protein expression levels of CYP2E1, SREBP-1c and FAS. ConclusionOur findings suggested that fermented hawthorn extract can markedly reduce body weight, ameliorate HFD-induced NAFLD in rats, and exhibits significant antioxidant effects. Its underlying mechanism may depend on the inhibition of CYP2E1, SREBP-1c, and FAS expression.

Changes of m6A Regulatory Proteins and Nrf2 Signaling Molecules in Liver Tissue of Type 2 Diabetes Mellitus Rats.

Both dysregulation of N6-methyladenosine (m6A) regulatory proteins and Nrf2 signaling molecules are involved in the process of injury to multiple tissues. However, changes of m6A regulatory proteins and Nrf2 signaling molecules in liver tissue of T2DM remain unclear. In present study, changes of m6A regulatory proteins (Mettl3, Mettl16, Fto, Alkbh5 and Ythdc2) and Nrf2 signaling molecules (Nrf2, Sod1, Ho-1, Gclc) were detected in the liver tissues of T2DM rats, which constructed by high fat-diet feeding and intraperitoneal injection of streptozotocin. Our results indicated that the morphology of liver tissues from T2DM rats showed obvious abnormalities, as well as levels of liver function indicators and expressions of Nrf2 signaling molecules Nrf2, Sod1, Ho-1 were significantly increased in T2DM rats when compared with those in corresponding control rats. More importantly, m6A regulatory proteins such as Mettl3, Mettl16, Fto, Alkbh5 and Ythdc2 were dramatically higher than those in control rat. In a word, m6A regulatory proteins and Nrf2 signaling molecules may significantly change in liver tissue of T2DM rats. And This provides clues and ideas for the study of liver injury in T2DM from the perspective of RNA epigenetics in the future.

Effect of Vernonia Cinerea Water Extract on the Protection of Liver Tissue in Chronic Nicotine-Treated Rats

Nicotine, a highly toxic alkaloid found in tobacco, is known for its addictive properties and systemic side effects, including carcinogenic potential and multi-organ damage. Recent evidence indicates that nicotine can significantly impair liver function and regeneration by promoting fibrogenesis and oxidative stress. This study aimed to investigate the protective effects of Vernonia cinerea (VC) against nicotine-induced liver damage in Wistar rats, focusing on inflammation and pro-fibrosis markers. Thirty male Wistar rats were divided into three groups: a control group, a nicotine group (1 mg/kg/day), and a nicotine plus VC group (1 mg/kg/day nicotine and 100 mg/kg/day VC). Liver tissues were examined using Hematoxylin and Eosin staining, and Masson's trichrome staining to evaluate histological changes. Kupffer cell counts were determined using a Panoramic digital slide scanner. Statistical analyses were conducted to compare the groups. Nicotine exposure led to significant liver damage, characterized by increased inflammation, collagen deposition, and disruption of liver architecture. VC supplementation ameliorated these effects, reducing inflammation and fibrosis markers. Kupffer cell counts were lower in the nicotine plus VC group compared to the nicotine group alone. Conclusion: VC demonstrates a protective role in mitigating nicotine-induced liver damage, highlighting its potential as a therapeutic agent for preventing liver fibrosis and maintaining liver health in nicotine-exposed individuals.

Melatonin alleviates arsenic-induced liver injury by regulating protein RKIP and enhancing antioxidant defencse mechanisms.

Arsenic (As) is a highly toxic metal and one of the main factors in cancer development through oxidative stress and production of reactive oxygen species. Prior research has demonstrated melatonin's potential as a free radical scavenger. Raf kinase inhibitory protein (RKIP) is an important regulator of intracellular signaling pathways that has been linked to various types of cancer. The aim of this research was to explore the influence of melatonin's antioxidant properties on the expression of the protein RKIP and the antioxidant status of liver tissue in rats that were exposed to arsenic. Thirty two male Wistar rats were divided into four groups of eight, including control, melatonin-treated (20 mg/Kg of melatonin), sodium arsenite-treated (5.5 mg/Kg of sodium arsenite), and melatonin + sodium arsenite-treated groups (combination) for 4 weeks. The expression level of protein RKIP was measured by Western blot, and malondialdehyde (MDA) content of the liver as well as the activities of antioxidant enzymes were measured. The data analyzed using one-way ANOVA (significance level of p < 0.05) and GraphPad Prism (9) software. Sodium arsenite treatment led to a significant decrease in RKIP protein expression and antioxidant enzyme activity, and an increase in liver MDA levels (p < 0.001). Conversely, melatonin treatment in the combination group resulted in a significant increase in RKIP protein expression and antioxidant enzyme activity and a decrease in liver MDA levels (p < 0.05). These findings suggest that melatonin can attenuate oxidative damage caused by arsenic in liver cells by enhancing RKIP protein expression and antioxidant enzyme activity.

Deacetylation of HnRNP U mediated by sirtuin1 ameliorates aged rat with liver fibrosis via inhibiting p53-related senescence and NLRP3-related inflammation

Senescence represents a major risk factor promoting liver fibrosis progression. Sirtuin 1 (SIRT1), an essential regulator of cellular senescence, may be involved in developing liver fibrosis. However, the role and mechanism of SIRT1 in liver fibrosis development were largely unknown. We constructed the liver fibrosis in aged rats induced by carbon tetrachloride (CCl4) and then transfected with GFP-SIRT1 adenoviral vectors. After that, we performed acetylomic analysis of liver tissue in aged rats to identify potential substrates of SIRT1. Furthermore, replicative senescent rat hepatocytes were pretreated with siRNA HnRNP U, SIRT1 adenoviral vectors, resveratrol, and siRNA SIRT1, following stimulation with H2O2. We found that the protein levels of SIRT1 and HnRNP U were down-regulation in aged rat liver fibrotic tissues, with an accumulation of NLRP3 inflammasome and activation of the p53/p21 pathway in liver tissue, as well as an increased level of plasma IL-1β secretion. In comparison, these effects were reversed by overexpressing SIRT1 with adenoviral vectors. Acetylation of HnRNP U and its sites at K28 and K787 might be potential targets for SIRT1-mediated liver fibrosis in aged rats. Silencing HnRNP U reduced H2O2-induced up-regulation expression of p53, p21, and NLRP3 inflammasome at protein levels. Additionally, H2O2 induced high acetylation of HnRNP U in senescent hepatocytes, whereas overexpressing SIRT1 with adenoviral vectors and resveratrol deacetylate HnRNP U to inhibit NLRP3 inflammasome and the p53/p21 pathway. Besides, the silence of SIRT1 aggravated H2O2-induced p53-related senescence and NLRP3-related inflammation in senescent hepatocytes. Our findings suggested that deacetylation of HnRNPU mediated by SIRT1 attenuated liver fibrosis in the elderly by inhibiting p53/p21 pathway and NLRP3-related inflammation.

Ontogeny of Hepatic Organic Cation Transporter-1 in Rat and Human.

The organic cation transporter (OCT)-1 mediates hepatic uptake of cationic endogenous compounds and xenobiotics. To date, limited information exists on how Oct1/OCT1 functionally develops with age in rat and human livers and how this would affect the pharmacokinetics of OCT substrates in children or juvenile animals. The functional ontogeny of rOct/hOCT was profiled in suspended rat (2-57 days old) and human hepatocytes (pediatric liver tissue donors: age 2-12 months) by determining uptake clearance of 4-[4-(dimethylamino)styryl]-N-methylpyridinium iodide (ASP+) as a known rOct/hOCT probe substrate. mRNA expression was determined in rat liver tissue corresponding to rat ages used in the functional studies, while hOCT1 mRNA expressions were determined in the same hepatocyte batches as those used for uptake studies. Maturation of rOct/hOCT activity and expression were evaluated by comparing values obtained at the various ages to the adult values. Relative to adult values (at 8 weeks), ASP+ uptake clearance in suspended rat hepatocytes aged 0, 1, 2, 3, 4, 5, and 6 weeks reached 26%, 29%, 33%, 37%, 72%, 63%, and 71%, respectively. Hepatic Oct1 mRNA expression was consistent with Oct activity (correlation coefficient of 0.92). In human hepatocytes, OCT1 activity was age dependent and also correlated with mRNA levels (correlation coefficient of 0.88). These data show that Oct1/OCT1 activities and expression mature gradually in rat/human liver, thereby mirroring the expression pattern of organic anion transporting polypeptide in rat. These high-resolution transporter ontogeny profiles will allow for more accurate prediction of the pharmacokinetics of OCT1/Oct1 substrates in pediatric populations and juvenile animals. SIGNIFICANCE STATEMENT: Organic cation transporter-1 (OCT1) represents a major drug uptake transporter in human liver. This study provides high-resolution data regarding the age-dependent function of OCT1 in the liver, based on in vitro experiments with rat and human hepatocytes obtained from donors between birth and adulthood. These ontogeny profiles will inform improved age-specific physiologically based pharmacokinetic models for OCT1 drug substrates in neonates, infants, children, and adults.

Improvement of Liver Function (AST and ALT) and Liver Tissue Catalase levels of Wistar rats induced with Alloxan by consuming Catfish oil extract

Background: Background: Type 2 Diabetes Mellitus (T2DM) is characterized by disrupted glucose metabolism, leading to hyperglycemia and insulin resistance, often associated with Secondary Hypertension (SH). Over 80% of SH patients exhibit glucose intolerance, with nearly 30% developing T2DM. There is a strong interaction between T2DM and NAFLD, representing a complex two-way relationship that influences the prognosis of the two diseases. Catfish oil extract boasts unsaturated fatty acids, including DHA, EPA, omega-3, vitamins A, B6, B12, D, and amino acids. Objective: This study aims to assess the impact of Pangasius sp. (catfish) oil extract administration on serum AST and ALT levels, as well as liver tissue MDA and CAT levels in alloxan-induced Wistar rats (Rattus norvegicus). Materials and Methods: Employing a pure experimental approach with a post-test-only control group design, three groups of 9 white male rats (Rattus norvegicus), along with one extra male rat, were included.K1 served as the negative control group (Wistar rats not subjected to any treatment). K2 acted as the positive control group (Wistar rats subjected to alloxan-induced diabetes at 150mg/kg BW). K3 represented the treatment group (diabetic model rats treated with catfish oil extract at 73mg/kg BW). Serum AST and ALT levels, as well as MDA and CAT levels in liver tissue, were measured at the study's conclusion. Results: The highest mean MDA levels in white rat liver tissue were K2 (3034.00 + 525.25 nmol/g), and the lowest was K3(2909.33+351.01nmol/g); the mean CAT liver tissue levels in rats the highest was K1 (1063.42+133.36U/mg), and the lowest was K3(894.78+132.93U/mg), the highest mean serum ALT levels of white rats was K2(230.34+63,58 U/L), and the lowest was K1(151.54+23.12 U/L) and the highest mean serum AST level in rats was K2(448.79+618.90U/L), and the lowest was K1(61.01+14.70U/L). Conclusion: Giving catfish oil supplementation can repair the damage in liver tissue, as evidenced by reductions in MDA levels and serum ALT and AST levels in diabetic model rats within the treatment group. Alloxan induction did not affect liver tissue CAT levels, as evidenced by a consistent decrease in liver tissue CAT levels in both the positive control and treatment groups.

Prenatal exposure to bisphenol AF causes toxicities in liver, spleen, and kidney tissues of SD rats

As a replacement for bisphenol A (BPA), bisphenol AF (BPAF) showed stronger maternal transfer and higher fetal accumulation than BPA. Therefore, concerns should be raised about the health risks of maternal exposure to BPAF during gestation on the offspring. In this study, SD rats were exposed to BPAF (0, 50, and 100 mg/kg/day) during gestation to investigate the bioaccumulation and adverse effects in liver, spleen, and kidney tissues of the offspring at weaning period. Bioaccumulation of BPAF in these tissues with concentrations ranging from 1.56 ng/mg (in spleen of males) to 55.44 ng/mg (in liver of females) led to adverse effects at different biological levels, including increased relative weights of spleen and kidneys, histopathological damage in liver, spleen, and kidney, organ functional damage in liver, spleen, and kidney, upregulated expression of genes related to lipid metabolism (in liver), oxidative stress response (in kidney), immunity and inflammatory (in spleen). Furthermore, dysregulated metabolomics was identified in spleen, with 217 differential metabolites screened and 9 KEGG pathways significantly enriched. This study provides a comprehensive insight into the systemic toxicities of prenatal exposure to BPAF in SD rats. Given the broad applications and widespread occurrence of BPAF, its safety should be re-considered.

Protective Effect of Carvacrol against Oxidative Damage in Aged Rats.

Aging affects cellular functions and impairs tissue homeostasis. Carvacrol, a polyphenolic compound, has been shown to exert a wide range of pharmacological effects, such as antioxidant, anti-inflammatory, and anticancer characteristics. This investigation aimed to evaluate the effect of carvacrol in elderly male rats. Carvacrol at a dose of 15 or 30 mg/kg was administrated daily per os for 60 days to aged rats. The liver, heart, and kidney samples were taken for the analysis of oxidative stress markers. Serum samples were used to evaluate liver enzymes (alanine transaminase (ALT) and aspartate aminotransferase (AST)). The levels of malondialdehyde (MDA) in the liver, heart, and kidney tissues of aged rats were higher. Conversely, the level of thiol was lower in the mentioned tissues than in the young control group. The levels of MDA in the liver, heart, and kidney tissues of aged rats were significantly reduced by carvacrol, which was accompanied by increased levels of total thiol. ALT and AST levels were higher in the serum of aged rats than in the young control ones. Carvacrol decreased ALT and AST levels in the serum of aged rats versus aged control rats. Carvacrol can be effective in protecting susceptible aged tissues and organs by increasing antioxidant defenses and decreasing liver enzymes.

Berberine Attenuates Acetamiprid Exposure-Induced Mitochondrial Dysfunction and Apoptosis in Rats via Regulating the Antioxidant Defense System.

Acetamiprid (ACMP) is a neonicotinoid insecticide that poses a significant threat to the environment and mankind. Oxidative stress and mitochondrial dysfunction are considered prime contributors to ACMP-induced toxic effects. Meanwhile, berberine (BBR) a natural plant alkaloid, is a topic of interest because of its therapeutic and prophylactic actions. Therefore, this study evaluated the effects of BBR on ACMP-mediated alterations in mitochondrial functions and apoptosis in rat liver tissue. Male Wistar rats were divided into four groups: (I) control, (II) BBR-treated, (III) ACMP-exposed, and (IV) BBR+ACMP co-treated groups. The doses of BBR (150 mg/kg b.wt) and ACMP (1/10 of LD50, i.e., 21.7 mg/kg b.wt) were given intragastrically for 21 consecutive days. The results showed that the administration of ACMP diminished mitochondrial complex activity, downregulated complex I (ND1 and ND2) and complex IV (COX1 and COX4) subunit mRNA expression, depleted the antioxidant defense system, and induced apoptosis in rat liver. BBR pre-treatment significantly attenuated ACMP-induced mitochondrial dysfunction by maintaining mitochondrial complex activity and upregulating ND1, ND2, COX1, and COX4 mRNA expression. BBR reversed ACMP-mediated apoptosis by diminishing Bax and caspase-3 and increasing the Bcl-2 protein level. BBR also improved the mitochondrial antioxidant defense system by upregulating mRNA expression of PGC-1α, MnSOD, and UCP-2 in rat liver tissue. This study is the first to evaluate the protective potential of BBR against pesticide-induced mitochondrial dysfunction in liver tissue. In conclusion, BBR offers protection against ACMP-induced impairment in mitochondrial functions by maintaining the antioxidant level and modulating the apoptotic cascade.

Mechanism of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata herbal pair in promoting hepatocellular regeneration in chronic acute liver failure based on HGF/PI3K/Akt signaling axis

Based on the hepatocyte growth factor(HGF)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling axis, this study investigated the therapeutic effect of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata(PRR-ALRP) her-bal pair on acute-on-chronic liver failure(ACLF) rats and its impact on hepatocellular regeneration. The rat model of ACLF was constructed by subcutaneous and tail vein injection of bovine serum albumin combined with intraperitoneal injection of lipopolysaccharides(LPS)+D-galactosamine(D-GalN). The rats were divided into normal control(NC) group, model(vehicle) group, PRR-ALRP(5.85 g·kg~(-1)) group, and hepatocyte growth factor granules(HGFG, 4.05 g·kg~(-1)) group. Hematoxylin-eosin(HE) staining was used to observe pathological changes in rat liver tissues. Serum alanine aminotransferase(ALT), aspartate transaminase(AST), and total bilirubin(TBIL) were detected using an automatic biochemical analyzer. The levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) inflammatory factors were detected by ELISA. Immunofluorescence staining was used to detect the positive expression of proliferating cell nuclear antigen(PCNA), antigen identified by monoclonal antibody(Ki67), and cell cycle protein B1(CyclinB1). Real-time fluorescence-based quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of HGF, growth factor receptor-bound protein 1(Gab1), PI3K, Akt, phosphorylated PI3K(p-PI3K), and phosphorylated Akt(p-Akt). The results showed that compared with the vehicle group, the PRR-ALRP group had reduced liver tissue pathological scores, improved liver function, and reduced inflammatory response, with enhanced PCNA, Ki67, and CyclinB1 fluorescence expression. Furthermore, compared with the model group, the PRR-ALRP group showed upregulated expression of HGF and Gab1 proteins, as well as activation of PI3K and Akt phosphorylation. These findings suggest that PRR-ALRP herbal pair exerts anti-liver failure effects by alleviating hepatocyte inflammatory damage and promoting hepatocellular regeneration, and its specific regulatory mechanism may be related to the activation of the HGF/PI3K/Akt signaling pathway.

The hepatoprotective potential of tannic acid against doxorubicin-induced hepatotoxicity: Insights into its antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

Doxorubicin (DOX), which is frequently used in cancer treatment, has limited clinical use due to adverse effects on healthy tissues, especially the liver. Therefore, it is necessary to research the molecular basis of DOX-induced organ and tissue damage and protective agents. In this study, we aimed to examine the protective effects of tannic acid (TA) against DOX-induced hepatoxicity in experimental rat models. Rats were randomly divided into four experimental groups: the untreated control, DOX, TA, and cotreatment (DOX + TA) groups. We investigated the antioxidant system's main components and oxidative stress indicators. Moreover, we examined alterations in the mRNA expression of critical regulators that modulate apoptosis, inflammation, and cell metabolism to better understand the underlying factors of DOX-induced liver toxicity. The results showed that DOX exposure caused an increase in MDA levels and a significant depletion of GSH content in rat liver tissues. Consistent with oxidative stress-related metabolites, DOX was found to significantly suppress both mRNA expression and enzyme activities of antioxidant system components. Moreover, DOX exposure had significant adverse effects on regulating the other regulatory genes studied. However, it was determined that TA could alleviate many of the negative changes caused by DOX. The results of the present study indicated that TA might be considered a versatile candidate that could prevent DOX-induced hepatotoxicity, possibly by preserving cell physiology, viability, and especially redox balance.

Transcription factor YY1 accelerates hepatic fibrosis development by activating NLRP3 inflammasome-mediated pyroptosis.

Hepatic fibrosis is the basis of multiple liver diseases and may eventually develop into hepatocellular carcinoma. Hepatic stellate cell (HSC) activation is a driving factor of hepatic fibrogenesis. In the liver microenvironment, liver cells and others play a crucial role in HSC activation. The liver tissues of CCl4-induced rats show excessive fibrosis, inflammation, and cell apoptosis. Yin Yang 1 (YY1) was highly expressed in hepatic fibrosis rats and TGF-β1-treated liver cells. In animal experiments, YY1 knockdown effectively attenuated CCl4-induced liver injury and pyroptosis-related IL-1β and IL-18 expression. In cellular experiments, NLRP3 inflammasome-mediated pyroptosis was activated by TGF-β1 treatment, while YY1 knockdown significantly inhibited the activation of the NLRP3 inflammasome, pyroptosis, and the secretion of IL-1β and IL-18. In addition, our data showed that TGF-β1-treated liver cell conditional medium markedly induced HSC activation, which was rescued by YY1 knockdown in liver cells. YY1 overexpression in liver cells contributed to the activation of TGF-β1-treated liver cell conditional medium in HSCs, however, this effect of YY1 was attenuated by NLRP3 inhibition. Overall, YY1 overexpression in liver cells contributed to HSC activation by facilitating IL-1β and IL-18 production via activating NLRP3 inflammasome-mediated pyroptosis, thus aggravating hepatic fibrogenesis. Our data indicate that YY1 may be a novel target for the treatment of hepatic fibrosis and associated liver diseases.