Liver Damage In Rats Research Articles

Hepatoprotective Effect of Padina gymnospora in Albino Wistar Rat; A Biochemical and Histopathological Studies

The methanolic extract of brown algae, Padina gymnospora (PG) was tested for hepatoprotective properties against paracetamol (acetaminophen, APAP)-induced liver damage in male albino Wistar rat through in-vitro model. Liver is damaged by the variation of serum enzymatic and biochemical markers, such as serum glutamate oxaloacetate transaminase (SGOT or AST), serum glutamate pyruvate transaminase (SGPT or ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), bilirubin, albumin, and lipid peroxidation and antioxidant status were measured by SOD and SDH. The study found that PG caused dose-dependent histopathological changes in the liver and kidney of the rats. While low doses caused minimal alterations, higher doses resulted in significant tissue damage. This suggests that, despite its therapeutic potential, careful consideration is needed regarding dosage to ensure safety. Acute toxicity studies revealed that the LD50 value exceeded 3 g/kg body weight. These results indicate that the methanolic extract of PG contains active compounds with antioxidant, anti-inflammatory, detoxification support, liver regeneration, cholesterol regulation, prevention of liver fibrosis and hepatoprotective effects against high doses of paracetamol-induced hepatotoxicity [Fig. 1].

Chidan Tuihuang granule modulates gut microbiota to influence NOD1/RIPK2 pathway in cholestatic liver injury recovery

BackgroundCholestatic liver injury (CLI), which occurs if bile acids are imbalanced and the liver becomes inflamed, is difficult to treat effectively ObjectiveWe investigated how the Chinese patent medicine Chidan Tuihuang granule (CDTH) ameliorates cholestatic liver injury with a focus on its effects on the NOD1/RIPK2 pathway and intestinal flora MethodsWe used an ANIT-induced SD rat model of CLI to evaluate the therapeutic effects of CDTH. The experimental design included control, model, UDCA (ursodeoxycholic acid) and CDTH treatment groups. UHPLC-Q-Orbitrap-HRMS was used to analyse the blood components of CDTH. The efficacy of CDTH was assessed by liver function tests, histopathological examination (HE and TUNEL staining), transmission electron microscopy, and ELISA to measure apoptosis and inflammatory markers. Mechanistic insights were obtained using transcriptomics and RT-qPCR, while alterations in the expression of key proteins were studied using western blotting, immunohistochemistry, and immunofluorescence. Furthermore, the impact of CDTH on the gut microbiota and its associated metabolite, meso-2,6-diaminopimelic acid (DAP), which is linked to NOD1 activation, was examined and confirmed through in vitro ResultsThe experimental results demonstrated a notable elevation in serum levels of AST, ALT, ALP, TBA, TBIL, and DBIL in the rats belonging to the model group, accompanied by the infiltration of inflammatory cells, hepatocyte degeneration, and necrosis in the liver tissue. CDTH administration significantly improved liver function and cholestasis indicators. Transmission electron microscopy and TUNEL staining revealed a marked reduction in liver cell apoptosis with CDTH treatment. ELISA results showed that CDTH effectively reduced inflammatory markers. Transcriptomic analysis showed that CDTH inhibited the NOD1/RIPK2 pathway, resulting in a significant decrease in the expression of NOD1, RIPK2 and associated genes in liver tissue. Gut microbiota analysis demonstrated that CDTH regulated intestinal flora structure, reducing the abundance of DAP-producing Gram-negative bacteria such as lactobacilli. In vitro experiments confirmed that CDTH enhanced cell viability by downregulating the DAP-mediated NOD1/RIPK2 signaling pathway secreted by intestinal bacteria ConclusionCDTH ameliorated liver damage in cholestatic rats by inhibiting the NOD1/RIPK2 signaling pathway through regulation of gut flora and downregulation of DAP metabolites.

Hepatocellular Changes on Paracetamol Induced Liver Damage in Long Evans Male Rats upon Green Tea Administration

Background: The liver is a vital organ that serves a number of purposes in our body. It may be harmed by pollutants, substances with toxic effects, and long-term, unchecked drug use. Green tea is a well-liked beverage that has gained popularity recently and may have hepatoprotective properties. Objective: To observe the effect of green tea (Camellia sinensis) on paracetamol induced liver damage in Long Evans male rats. Methods: From July 1st, 2018, to June 30th, 2019, this study was conducted in the Department of Physiology at Sir Salimullah Medical College (SSMC), Dhaka. For the purpose of the study, thirty (30) male Long Evans rats, weighing between 150 and 200 grams and 90 to 120 days old, appeared to be in good health. They were split into two groups after 14 days of acclimatization: Group A, which served as the control group, and Group B, which served as the experimental group (green tea pretreatment and paracetamol treated). Group A1 (baseline control group) and group A2 (paracetamol treated control group) comprised the subdivided control group. There were ten rats in each of these groups. For 28 days, the rats were all fed a baseline diet. The baseline control group was given normal saline (20 ml/kg/day) orally every day for 28 days in addition to their basal diet. For the final three days of the study—the 26th and 28th—the paracetamol-treated control group was given oral paracetamol at a dose of 1.5 g/kg/day. During the final three days of the study period (the 26th and 28th days), the experimental group was given oral paracetamol (1.5g/kg/day) and an ethanolic extract of green tea (500 mg/kg/day) for a total of 28 days. On day 29, every rat was sacrificed. Following the sacrifice, liver samples were taken. Hepatic contents of malondialdehyde (MDA) were measured by using standard laboratory method. Histopathology of liver was also done by using standard laboratory procedure in the department of pathology, SSMC. Version 22 of the Statistical Package of Social Science (SPSS) for Windows was used to do the statistical analysis. The data were displayed as mean±SD. To compare the results, one-way ANOVA, post hoc Bonferroni, and Chi-square tests were used, where appropriate. A p value of less than 0.05 was regarded as significant. Result: When compared to the baseline control group, the mean malondialdehyde concentration in the liver was significantly (p) greater in the green tea pretreatment, paracetamol treated, and control groups who received paracetamol treatment. Once more, the groups treated with green tea and paracetamol had mean malondialdehyde concentrations in their livers that were significantly (p) lower than those of the paracetamol group. Additionally, 0% of the rats in the baseline control group, 100% of the rats in the paracetamol-treated group, and 30% of the rats in the green tea-pretreated and paracetamol-treated group had abnormal histological findings of the liver. Conclusion: This study revealed that green tea has hepatoprotective effect against paracetamol induced liver damage in Long Evans male rats. Bangladesh Crit Care J September 2024; 12 (2): 145-152

Effects of licorice root (Glycyrrhiza glabra) extract on the livers of obese rats.

We have investigated anti-obesity effects of the extract of licorice (Glycyrrhiza glabra) root in rats with diet-induced obesity and hyperlipidemia by using histopathological and biochemical methods. Thirty-two Wistar albino rats were divided to four groups of eight: normal control (C), high fat diet (HFD), high fat Diet + Glycyrrhiza glabra (HFD+M), and normal diet with Glycyrrhiza glabra (M). The high fat diet contained 300 g/kg fat (4000 kcal/kg); the daily dosage of Glycyrrhiza glabra extract was 1g/kg body weight by orogastric gavage. Supplementation of Glycyrrhiza glabra extract dramatically reduced increases in body weight caused by the induction of obesity. A hepatoprotective effect of Glycyrrhiza glabra extract was supported by the almost normal histology in the livers of the HFD+M rats, in contrast to the degenerative changes in the HFD rats, which included macrovesicular and microvesicular fat deposits, hydropic degeneration, dilatation of sinusoids and coagulation necrosis of some hepatocytes. Serum levels of alanine transaminase (ALT), aspartic transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), cholesterol (HDL and LDL) and triglycerides, were ameliorated by Glycyrrhiza glabra extract treatment. We conclude that Glycyrrhiza glabra extract given together with HFD could prevent obesity and reduce liver damage in rats.

Bie Jia Jian pill ameliorates BDL-induced cholestatic hepatic fibrosis in rats by regulating intestinal microbial composition and TMAO-mediated PI3K/AKT signaling pathway

Ethnopharmacological relevanceAs a compound of traditional Chinese medicine (TCM), Bie Jia Jian pill (BJJP) is extensively used to treat the clinical chronic liver disease. Nevertheless, the specific mechanism through which BJJP affects hepatic fibrosis (HF) remains unknown. Aim of the studyTo explore the role and potential mechanism of BJJP involved in treating HF. Materials and methodsHF model of Sprague-Dawley (SD) rats was induced by a bile duct ligation (BDL). The function of BJJP involved in the intestinal microbiota (IM) and its metabolites in BDL-induced HF rats were explored through the 16S rRNA sequencing and untargeted metabolomics technologies. Network pharmacology was used to forecast mechanism underlying BJJP's anti-HF effects, which were validated in BDL-induced rats and trimethylamine N-oxide (TMAO)-induced LX-2 and HSC-T6 cells. ResultsBJJP effectively ameliorated pathological liver damage, inflammation, and fibrosis of the BDL-induced HF rats. BJJP regulated IM diversity and composition and interfered with trimethylamine (TMA)-flavin monooxygenase 3 (FMO3)-TMAO process. In vitro, BJJP significantly inhibited the TMAO-induced activation of hepatic stellate cells (HSCs) (rat HSC cell line, HSC-T6; human HSC cell line, LX-2). Network pharmacology results demonstrated that PI3K/AKT signal pathway is crucially involved in BJJP treatment of HF. Further research revealed that BJJP inhibited the PI3K/AKT signal pathway in BDL-induced HF rats. Moreover, TMAO activated the PI3K/AKT pathway, whereas BJJP suppressed TMAO-induced activation. Subsequent intervention with 740Y-P (the PI3K agonist) successfully neutralized the repression effect on PI3K/AKT signal pathway by BJJP. ConclusionThese results clearly show that BJJP attenuates HF by regulating the IM, as well as inhibiting PI3K/AKT pathway mediated by TMAO.

Therapeutic potential of aquatic Stevia extract in alleviating endoplasmic reticulum stress and liver damage in streptozotocin-induced diabetic rats.

Misfolded proteins accumulate in the liver due to endoplasmic reticulum stress (ERS) caused by high blood glucose levels in diabetes. This triggers the unfolded protein response (UPR), which if persistently activated, results in cellular dysfunction. Chronic ER stress increases inflammation, insulin resistance, and apoptosis. There is growing interest in using native plants and traditional medicine for diabetes treatment. The stevia plant has recently gained attention for its potential therapeutic effects. This study investigates the protective effects of aquatic stevia extract on liver damage, ER stress, and the UPR pathway in streptozotocin (STZ)-induced diabetic rats. Rats were randomly divided into four groups: a control group that received 1ml of water; a diabetic group induced by intraperitoneal injection of STZ (60mg/kg); a diabetic group treated with metformin (500mg/kg); and a diabetic group treated with aquatic extracts of stevia (400mg/kg). After 28 days, various parameters were assessed, including inflammatory markers, oxidative stress indices, antioxidant levels, gene expression, stereology, and liver tissue pathology. Compared to the diabetic control group, treatment with stevia significantly decreased serum glucose, liver enzymes, inflammatory markers, and oxidative stress while increasing body weight and antioxidant levels. Additionally, stevia extract manipulated UPR gene expression and reduced apoptosis pathway activation. Histological examination revealed improved liver tissue morphology in stevia-treated diabetic rats. These findings suggest that aquatic stevia extract mitigates ER stress in diabetic rats by modulating the IRE-1 arm of the UPR and apoptosis pathways, highlighting its potential therapeutic benefits for diabetes-related liver complications.

Boosting impacts of Acacia nilotica against hepatic toxicity induced by gentamicin: biochemical, anti-inflammatory and immunohistochemical study.

It seems that gentamicin's toxicity to the liver is caused by reactive oxygen species production. The antioxidant and anti-inflammatory properties of Acacia nilotica extract (AN) have been demonstrated in recent studies. This research focused on how AN's extract affected gentamicin-induced liver damage in rats. Twenty-four Wister rats of male type were divided into four groups: first group received saline as a control, second group received AN (5%) for fifteen days, group three received daily intraperitoneal injections of gentamicin (100mg/kg) for fifteen days, and group four, as mentioned in groups 2 and 3, also received gentamicin injections and AN extraction (5%) for fifteen days. In order to conduct biochemical analysis, serum was extracted. Histopathology, immunohistochemistry analyses for hepatic toxicity were all performed on the collected tissue samples. Serum levels of ALT, AST, total bilirubin, and GGT were all elevated after using gentamicin. The inflammatory cytokines)IL-1, TNF-α and IL-6(, all were increased in gentamycin-injected group. There were showing deformity of bile duct, hepatocellular necrosis and infiltration of inflammatory cells congestion of portal vein, and hepatic sinusoids besides fibrosis of portal area (white arrows), hypertrophy in gentamycin-injected group compared to AN plus gentamycin administered rats. There were upregulation in the immunoreactivity of COX-2, IFNkB and TGF-beta1 (TGF-β1) in gentamycin intoxicated rats. When gentamicin and AN were administered together, hepatic biomarkers, inflammatory cytokines, histological, and immunohistochemical markers were all ameliorated by AN administration.

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.

Protective effects of herbacetin against polystyrene microplastics-instigated liver damage in rats

Polystyrene microplastics (PS-MPs) are raising global concerns as they have tendency to induce adverse effects on organisms. Herbacetin (HBN) is a natural flavone that shows diverse biological activities. Therefore, the current study was designed to evaluate the curative role of HBN against PS-MPs provoked hepatic damage. Forty-eight rats were divided into 4 groups, control, PS-MPs-intoxicated (0.01 mg/kg), PS-MPs + HBN co-treated (0.01 mg/kg + 40 mg/kg) and HBN only treated (40 mg/kg) group. The experiment was conducted for 30 days. PS-MPs administration reduced the expressions of Nrf-2 as well as anti-oxidants genes and increased Keap-1 expression. It also lessened the activities of superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and heme oxygenase-1 (HO-1) and glutathione (GSH) level, while elevating the levels of MDA and ROS. Additionally, PS-MPs exposure augmented the levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine transaminase (ALT). Furthermore, there was an upsurge in the levels of inflammatory indices in PS-MPs treated group. PS-MPs also upregulated Caspase-3 and Bax expression whereas, decreased Bcl-2 expression. Nevertheless, HBN treatment recovered all the impairments due to its anti-apoptotic, anti-oxidant and anti-inflammatory and hepatoprotective nature. Therefore, it is deduced that HBN could be used as a potential therapeutic agent to counter PS-MPs induced hepatic toxicity.

Protective effects of curcumin against valproic acid induced brain kidney and liver damage in rats

Valproic acid (VPA) is a broad-spectrum drug that is now widely used as an antiepileptic. Although VPA has positive therapeutic effects, it also causes various toxic effects in tissues. Curcumin, a natural antioxidant found in ginger, has antibacterial and antiinflammatory activity. In this study, the toxic effects of VPA on brain, kidney, and liver tissues and the protective activity of curcumin against these effects were investigated. In this study, male Wistar-Albino rats were used. Rats were divided into 4 groups control, VPA, CUR, and CUR + VPA. Rats were administered intraperitoneal VPA and CUR intragastrically. In the study, MDA, SOD, IL-6, and IL-18 levels were measured by the ELISA method in rats. It was observed that VPA triggered oxidative stress and inflammation in tissues, while CUR administration positively regulated these parameters. Studies also showed that VPA increased the expressions of TNF-α and NF-kB in tissues, but CUR administration downregulated these expressions The findings revealed that CUR protects by preventing the oxidative stress and inflammation caused by VPA in the tissues and may be an important agent in reducing the side effects of this drug used as an antiepileptic.

Walnut kernel against liver damage induced by salt processed Psoraleae Fructus through regulating bile acid metabolism in ovariectomized rats

Walnut kernel (WK) is a globally popular health food known for its potent antioxidant properties. WK shows a promising prospect in protecting against liver damage induced by salt processed psoraleae fructus (SPF). This study explored the impact of WK in mitigating liver damage induced by SPF in an ovariectomized (OVX) rat model. Serum metabolomics was employed to explore potential detoxification mechanisms. The levels of Farnesoid X receptor (FXR), Bile salt export pump (BSEP), and Cholesterol 7α-hydroxylase (CYP7A1) proteins were determined through western blot analysis. The results demonstrated that WK exhibits a noteworthy protective effect against liver damage induced by SPF. The WK normalized the metabolic disorder and reversed sixteen liver injury biomarkers and five metabolic pathways induced by SPF. These results demonstrated that WK exhibits a protective effect against SPF-induced liver damage in OVX rats by regulating bile acid metabolism.

Chronic aluminium chloride exposure induces redox imbalance, metabolic distress, DNA damage, and histopathologic alterations in Wistar rat liver.

Aluminium, a ubiquitous environmental toxicant, is distinguished for eliciting a broad range of physiological, biochemical, and behavioural alterations in laboratory animals and humans. The present work was conducted to study the functional and structural changes induced by aluminium in rat liver. Twenty five adult male Wistar rats (150-200 g) were randomly divided into five groups; control group and four Al-treated groups viz: Al 1 (25mg AlCl3/kg b.wt), Al 2 (35mg AlCl3/kg b.wt), Al 3 (45mg AlCl3/kg b.wt), and Al 4 (55mg AlCl3/kg b.wt). Rats in the aluminium-treated groups were administered AlCl3 for 30 days through oral gavage. Aluminium significantly increased the serum levels of liver function markers (ALT, AST, and ALP), phospholipids, and cholesterol. The activities of hepatocyte membrane (ALP, GGT, and LAP) and carbohydrate metabolic (G6P, F16BP, HK, LDH, MDH, ME, and G6PDH) enzymes were significantly altered by AlCl3 administration. Prolonged Al exposure induced oxidative stress in the liver, as evident by significant hepatocellular DNA damage, increased lipid peroxidation, and decreased non-enzymatic and enzymatic antioxidants. The toxic effects observed in this study were AlCl3 dose-dependent. Histopathological examination of liver sections revealed enlargement of sinusoidal spaces, derangement of the hepatic chord, loss of discrete hepatic cell boundaries, congestion of hepatic sinusoids, and degeneration of hepatocytes in Al-intoxicated rats. In conclusion, aluminium causes severe hepatotoxicity by inhibiting the hepatocyte membrane enzymes and disrupting the liver's energy metabolism and antioxidant defence.

Hepatoprotective potential of taxifolin in type 2 diabetic rats: modulation of oxidative stress and Bcl2/Bax/Caspase-3 signaling pathway.

Diabetes mellitus (DM) is a global metabolic problem. Several factors including hyperglycemia, oxidative stress, and inflammation play significant roles in the development of DM complications. Apoptosis is also an essential event in DM pathophysiology, -with B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) determining apoptotic susceptibility. The present study aimed to elucidate the protective effects of two doses of taxifolin (TXF) on liver damage in diabetic rats and explore the possible mechanisms of action. DM was induced in eighteen rats through intraperitoneal injections of 50mg/kg streptozotocin and 110mg/kg nicotinamide. Diabetic rats received daily oral intubation of 25 and 50mg/kg TXF for 3 months. In the untreated diabetic group, there was a significant increase in fasting and postprandial glucose levels, glycosylated hemoglobin A1C (HbA1c), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while insulin and adiponectin levels decreased significantly. Both TXF doses mitigated hyperglycemia, regulated cytokine production, and increased insulin level. Gene expressions and protein levels of Bax, caspase 3, and cytochrome c were significantly increased, while Bcl-2 was significantly decreased in the livers of diabetic rats, effects that were significantly ameliorated after TXF treatment. The results of the TUNEL assay supported the apoptotic pathway. Additionally, TXF significantly decreased lipid peroxidation and enhanced antioxidant enzyme activity in diabetic rats. Liver enzymes and histopathological changes also showed improvement. TXF mitigated diabetes-associated hepatic damage by reducing hyperglycemia, oxidative stress, inflammation, and modulating anti-/pro-apoptotic genes and proteins. A dose of 50mg/kg TXF was more effective than 25mg/kg and is recommended for consumption.

Flavone improves liver damage in nicotine-exposed rats via the Nrf2/HO-1 pathway

Objective: To assess the hepatoprotective effects of flavone on nicotine-induced liver damage. Methods: Thirty-six rats were allocated into six groups: the control group, the nicotine group, the flavone alone groups (10 and 25 mg/ kg/body weight), and the nicotine groups treated with flavone (10 and 25 mg/kg/body weight). Liver function, oxidative stress, Nrf2 pathway (HO-1, Nrf2, and Keap-1), and inflammatory markers (IL-17, TNF-α, and NF-κB) were evaluated. Additionally, a histopathological examination of liver tissues was performed. Results: Nicotine increased liver damage, inflammation, and oxidative stress. However, flavone suppressed nicotine-induced liver enzymes, oxidative stress, and inflammation, as manifested by increased antioxidants and decreased malondialdehyde level, liver enzymatic activities, and inflammatory markers. Flavone (10 and 25 mg/kg/body weight) also reduced the level of Keap-1 and increased HO-1 and Nrf2 levels in the liver of nicotine-exposed rats. Conclusions: Flavone has hepatoprotective properties and may slow the progression of liver injury by reducing oxidative stress, liver enzymes, and inflammation possibly via the Nrf2 pathway.

Guizhi Fuling Wan attenuates tetrachloromethane-induced hepatic fibrosis in rats via PTEN/AKT/mTOR signaling pathway

Ethnopharmacological relevanceTreatment options for hepatic fibrosis, a prevalent liver condition closely linked to cirrhosis, are currently limited. While Guizhi Fuling Wan (GFW), a pill derived from traditional Chinese herbs, has been reported to possess hepatoprotective properties, its therapeutic effect and mechanism in hepatic fibrosis remain elusive. Aim of the studyThis study aimed to evaluate the anti-fibrotic impact of GFW and its underlying mechanisms in both in vivo and in vitro settings. Materials and methodsTetrachloromethane (CCl4) was used to induce hepatic fibrosis in male rats. In vitro, activation of hepatic stellate cells (HSCs) was triggered by platelet-derived growth factor-BB (PDGF-BB). In vivo, liver function, pathological alterations, and HSC activation were evaluated. Additionally, the impact of GFW on the activated phenotypes of Lieming Xu-2 (LX-2) cells was examined in vitro. Network pharmacology was employed to identify the potential targets of GFW in hepatic fibrosis. Lastly, the impact of GFW on the PTEN/AKT/mTOR pathway and PTEN ubiquitination in HSCs was investigated. ResultsGFW alleviated CCl4-induced liver damage and scarring in rats in a dose-dependent manner and suppressed HSC activation in vivo. Moreover, GFW inhibited the proliferation, migration, differentiation, and extracellular matrix (ECM) production of activated HSCs in vitro. GFW also promoted autophagy and apoptosis of HSCs. Meanwhile, network pharmacology and in vitro studies suggested that GFW inhibits the AKT/mTOR pathway by preventing PTEN degradation by suppressing ubiquitination. ConclusionGFW attenuates Ccl4-induced hepatic fibrosis in male rats by regulating the PTEN/AKT/mTOR signaling pathway, positioning it as a potential candidate for the treatment of hepatic fibrosis.

تأثير المستخلص المائي لغانوديرما لوسيدوم كعامل وقائي للكبد ضد الضرر الناجم عن الكيتوبروفين في الفئران الذكور.

This study's objective was to assess the protective impact of an aqueous extract of G. lucidum against ketoprofen-induced liver damage in male albino rats. Twenty-eight healthy adult male albino rats were divided into four groups (7 rats in each). Group 1: normal control group; Group 2: rats were given ketoprofen (50mg/kg body weight) daily for two weeks, Group 3: rats were given G. lucidum (300mg/kg body weight) daily for four weeks, and Group 4: rats were given ketoprofen (50mg/kg body weight) daily for two weeks, then were given G. lucidum (300mg/kg body weight) daily for four weeks. The histological preparations of the liver of rats treated by ketoprofen showed degenerating hepatocytes, widened with congested central vein with inflammatory cell infiltration, necrotic areas, widened with congested portal vein, thickening wall of central vein enclosed by fibrotic area, and sever haemorrhage. Whereas, the rats which treated by therapeutic dosages showed improved of hepatic architecture with hepatocytes structures, normal sinusoids, minimal congested central vein, improved in the portal area with few inflammatory cell infiltrations, normal sinusoids, and minimal congested portal vein. In conclusion, this study shows that the G. lucidum has protective effects against ketoprofen induced hepatic injury in adult male albino rats.

The Liver of Young and Old Female Rats Exhibits Heightened Susceptibility to Dichlorvos Exposure

Exposure to industrial and agricultural environmental contaminants has been shown to produce deleterious effects on different organs of the human body. Dichlorvos [O, O-dimethyl O-(2,2-dichlorovinyl) phosphate, DDVP] is a major organophosphate pesticide used mostly in developing countries for domestic and agricultural insect control. The toxic effects of DDVP have been reported on many organs. However, its gender and age-dependent effects on the liver are yet to be documented. This study investigated the influence of gender and age on liver damage in male and female rats exposed to DDVP. Animals were divided into control and experimental groups with age and gender classification. Using age, rats were classified into young, middle-aged, and old age groups. Rats in the experimental groups were exposed to DDVP from 8 am to 12 noon for five weeks. Rats were subsequently euthanized and liver tissues were harvested for biochemical assay. Glutamyl transferase (GGT), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH), Albumin, and conjugated bilirubin were assayed using ELISA kits. Statistical analysis was done using two-way ANOVA, followed by Tukey post-Hoc test at significance level of p<0.05. Our study found that DDVP exposure caused liver damage in female rats only with significant elevation in liver enzymes such as ALP, ALT, AST, and LDH. However, the male rats showed more resistance to DDVP exposure. The liver damage observed in female rats was age-dependent, with young and old rats showing higher susceptibility compared to middle-aged female rats. Nutritional and pharmacological strategies are recommended to mitigate the effect of DDVP exposure, particularly in populations at higher risk of exposure.

Hepatoprotective Activity of Patra Swarasa of Guduchi (Tinospora Cordifolia) Against- Paracetamol Induced

Guduchi (Tinospora cordifolia (Willd.) Miers], Menispermaceae family, it is important medicinal plant is widely distributed through India. It is categorized as "Rasayana" and the whole plant is used medicinally. The aim of the present study is to evaluate the protective effect of Guduchi patra swaras against paracetamol induced liver damage in Wister albino rats. Material & Methods: Wistar Albino rats (140-250g) will be divided into 6 group and each group 6 rats, into control group, paracetamol control, standard group, test group. The test drug Guduchi patra swarasa was administered orally for 10 consecutive days and two dose of the toxicant (paracetamol) were administered orally to each group, on two alternate days i.e., 7th and 9th day, 1hr after test drug administration. After 48 hours of toxicant paracetamol, and standard group. The blood was collected in EDTA tube and sent for biochemistry laboratory for biochemical investigations. Result: The analysis of serum biochemical parameters shows that administration of paracetamol leads to significant change in majority of the parameters. The overall activity profile indicated reversal of important parameters like SGOT, SGPT, total bilirubin, total protein, blood sugar level, serum globulin, serum albumin, serum total cholesterol and serum triglycerides. All three test groups of Guduchi patra Swarasa administered are found to be effective heapto-protective especially based on histo-pathological study. Among the three groups, the double dose group and therapeutic group has shown good results in comparison with the other two groups. Conclusion: In the present study, the overall activity profile of Guduchi patra Swarasa administered are found to be effective hepatoprotective among the three groups therapeutic double dose shows good results in comparison with the other group.

Proteome profiling, biochemical and histological analysis of diclofenac-induced liver toxicity in Yersinia enterocolitica and Lactobacillus fermentum fed rat model: a comparative analysis.

Diclofenac is a hepatotoxic non-steroidal anti-inflammatory drug (NSAID) that affects liver histology and its protein expression levels. Here, we studied the effect of diclofenac on rat liver when co-administrated with either Yersinia enterocolitica strain 8081 serotype O:8 biovar 1B (D*Y) or Lactobacillus fermentum strain 9338 (D*L). Spectroscopic analysis of stool samples showed biotransformation of diclofenac. When compared with each other, D*Y rats lack peaks at 1709 and 1198cm-1, while D*L rats lack peaks at 1411cm-1. However, when compared to control, both groups lack peaks at 1379 and 1170cm-1. Assessment of serum biomarkers of hepatotoxicity indicated significantly altered activities of AST (D*Y: 185.65 ± 8.575 vs Control: 61.9 ± 2.607, D*L: 247.5 ± 5.717 vs Control: 61.9 ± 2.607), ALT (D*Y: 229.8 ± 6.920 vs Control: 70.7 ± 3.109, D*L: 123.75 ± 6.068 vs Control: 70.7 ± 3.109), and ALP (D*Y: 276.4 ± 18.154 vs Control: 320.6 ± 9.829, D*L: 298.5 ± 12.336 vs Control: 320.6 ± 9.829) in IU/L. The analysis of histological alterations showed hepatic sinusoidal dilation with vein congestion and cell infiltration exclusively in D*Y rats along with other histological changes that are common to both test groups, thereby suggesting more pronounced alterations in D*Y rats. Further, LC-MS/MS based label-free quantitation of proteins from liver tissues revealed 74.75% up-regulated, 25.25% down-regulated in D*Y rats and 51.16% up-regulated, 48.84% down-regulated in D*L experiments. The proteomics-identified proteins majorly belonged to metabolism, apoptosis, stress response and redox homeostasis, and detoxification and antioxidant defence that demonstrated the potential damage of rat liver, more pronounced in D*Y rats. Altogether the results are in favor that the administration of lactobacilli somewhat protected the rat hepatic cells against the diclofenac-induced toxicity.

Effects of Ethanolic Leaves Extract of Irvingia gabonensis on Arsenic Trioxide-Induced Liver damage in Wistar rats

Effects of Ethanolic Leaves Extract of Irvingia gabonensis on Arsenic Trioxide-Induced Liver damage in Wistar rats