Adult Rat Liver Research Articles

Potential cytotoxic effect of caffeinated and non-caffeinated carbonated soft drinks on liver and pancreas of adult male Albino rats; (biochemical, histological and DNA study)

Potential cytotoxic effect of caffeinated and non-caffeinated carbonated soft drinks on liver and pancreas of adult male Albino rats; (biochemical, histological and DNA study)

The Possible Protective Effect of Vitamin C Against Sildenafil Citrate Affected Liver of Adult and Senile Male Albino Rats (Light and Electron Microscopic Study)

The Possible Protective Effect of Vitamin C Against Sildenafil Citrate Affected Liver of Adult and Senile Male Albino Rats (Light and Electron Microscopic Study)

Bisphenol A enhances apoptosis, fibrosis, and biochemical fluctuations in the liver of adult male rats with possible regression after recovery.

Bisphenol A (BPA) is an environmental contaminant that might be harmful. Human exposure to BPA can occur during the fetal and postnatal periods and extends throughout life. This study aimed to estimate the effects of oral administration of BPA on rat liver and assess the possibility of recovery after cessation. Adult male albino rats were orally administered with BPA (50 mg/kg body weight) for 8 weeks, and then one group was left to recover for 4 weeks. Histological, immunohistochemical, biochemical, and quantitative real-time polymerase chain reaction assessments were performed. Loss of hepatic architecture, vascular dilatation congestion, and exudation, as well as cellular vacuolation, fat accumulation, and pyknotic nuclei were detected. Furthermore, inflammatory infiltration, localized metaplasia, and excessive collagen deposition in the portal triad were observed. Expression of Bcl-2-associated X protein and transforming growth factor beta 1 was prominent, denoting apoptosis and fibrosis. After the administration of BPA, serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, and low-density lipoproteins were enhanced. Additionally, total protein, albumin, and high-density lipoproteins decreased. After a recovery for 4 weeks, hepatic cellular and vascular pathologies returned to normal, except for some inflammatory infiltration. Regarding biochemical affection, most of the parameters were directed toward normal during recovery. However, most of them were still significantly different from controls. This explored BPA hepatotoxicity from structural and functional aspects, and the possible spontaneous reversibility was confirmed. However, the precise mechanisms underlying hepatotoxicity or recovery need more in-depth investigations.

Protective Effect of Ocimum Gratissimum Against Lead Induced Histological Changes in Rabbit Liver

Background: Since it is well-established that lead exposure can have negative effects on hematological, biochemical, and hepatic parameters, a significant number of research efforts have been focused on antioxidants that are capable of treating as well as preventing these alterations. Objective: The purpose of this study was to explore the influence of Ocimum Gratissimum (OG) extract on the hemato-biochemical parameters of the livers of adult Wistar rats and the lead-induced toxicity of the livers. Method: For the aim of this investigation, a total of 70 adult Wistar rats were separated into seven groups, with each group containing 10 rats. Group A acted as the control group, Group B received 120 mg/kg of lead, and Group C received 375 mg/kg of OG. Group A was the only group that received no treatment. The role of the control group was played by Group A. Before administering the OG dosages of 375 and 750 mg/kg to Group D and Group E, respectively, a lead dose of 120 mg/kg was administered to both groups. In Group F, participants received 375 mg/kg of OG extract followed by 120 mg/kg of lead, whereas in Group G, participants received 120 mg/kg of lead followed by 1,190 mg/kg of ascorbic acid. After the conclusion of each oral treatment, which lasted a total of 21 days, the animals were slaughtered and their blood and liver tissues were collected for subsequent histological and biochemical testing. The results of these tests will be shown in the following paragraphs. Results: The research led to the discovery that the Control group had a rise in their average body weight, but the B group experienced a fall in their weight. The findings of the biochemical tests revealed that when compared to the Control group and the other treatment groups, the levels of liver enzymes such as ALT, AST, GGT, and ALP in Group B were considerably higher than in the other treatment groups (p 0.05). The results of the histological analysis of the liver tissues revealed degenerative alterations, such as localized necrosis and aggregated inflammatory cells in Group B. These findings were found in the liver tissues of the group B patients. In contrast, the liver tissue in Groups D, E, F, and G that had been treated with the extract exhibited ameliorative alterations. These results may be seen in the table below.

Age-Specific Features of the Levels of Reference Proteins Actin, Tubulin, and GAPDH in Different Organs of Male Wistar Rats.

Western blot analysis is used for evaluation of the level of proteins production in organs and tissues, and housekeeping proteins GAPDH, actin, and tubulin are usually used as the reference proteins. The signal of the target protein is normalized to the corresponding signal of the reference protein. The data on the intensity of actin, tubulin, and GAPDH synthesis are fragmentary: their expression differs in different organs and can vary depending on age, which is often not taken into account in experimental studies. We studied the features of the production of reference proteins in the liver, heart, brain, and lungs of newborn, prepubertal, and adult male Wistar rats. Age-related differences in the expression of β-actin, β-tubulin, and GAPDH in the myocardium and dorsal prefrontal cortex were revealed. GAPDH expression in the dorsal prefrontal cortex in adult rats was significantly higher than in prepubertal rats; GAPDH expression in the myocardium of adult rats was significantly higher than in newborns. The level of actin in the dorsal prefrontal cortex in newborn rats was significantly higher than in prepubertal and adult rats. In the liver and lungs, the expression of actin, tubulin, and GAPDH did not differ in newborn, prepubertal, and adult rats. When choosing the reference protein for Western blotting, animals age and the studied organ should be taken into account.

Estimation of Postmortem Interval by Light and Electron Microscopic Findings in the Liver of Adult Male Albino Rats

Estimation of Postmortem Interval by Light and Electron Microscopic Findings in the Liver of Adult Male Albino Rats

Cannabidiol (CBD) Dosing: Plasma Pharmacokinetics and Effects on Accumulation in Skeletal Muscle, Liver and Adipose Tissue.

Oral cannabidiol (CBD) consumption is widespread in North America and Europe, as it has analgesic, neuroprotective and antitumor effects. Although oral CBD consumption in humans affords beneficial effects in epileptic and inflammatory states, its pharmacokinetics and subsequent uptake into tissue are largely unknown. This study investigated plasma pharmacokinetics and accumulation of CBD in gastrocnemius muscle, liver and adipose tissue in adult rats following oral gavage. CBD was fed relative to body mass at 0 (control), 30, 115, or 230 mg/Kg/day for 28 days; with 6 males and 6 females per dosing group. Pharmacokinetics were assessed on day 1 and day 28 in the group receiving CBD at 115 mg/Kg/day. The rise in tissue CBD was closely related to specific pharmacokinetic parameters, and adipose tissue levels were ~10 to ~100 fold greater than liver or muscle. Tissue CBD levels were moderately correlated between adipose and muscle, and adipose and liver, but were highly correlated for liver and muscle. CBD feeding resulted in several gender-specific effects, including changes in pharmacokinetics, relationships between pharmacokinetic parameters and tissue CBD and differences in tissue CBD levels. CBD accumulation in mammalian tissues has the potential to influence receptor binding and metabolism; therefore, the present findings may have relevance for developing oral dosing regimens.

Evaluation of the protective effect of melatonin on histological changes in the liver of adult male rats treated with gemcitabine

Melatonin is an endocrine hormone, produced by the pineal gland from the amino acid tryptophan. Melatonin level in the body according to a predetermined cycle and are affected by light received. Gemcitabine is an anti-cancer drug. The mechanism of action of gemcitabine affects the properties of the cellular phase and mainly destroys the cells that are making DNA (phase-s). Nephrotoxic side effects of gemcitabine have been reported in patients receiving this drug medication. Melatonin is a potent free radical scavenger and antioxidant and has protective effects against ischemic damage. The aim of the present study was to investigate the protective effect of melatonin on histological changes in the liver of adult male rats treated with gemcitabine and to evaluate the effects of different doses of melatonin on the protection of adult liver cells treated with gemcitabine. This experimental study was performed on male Wistar rats weighing approximately 250±20g and aged 8 weeks. Mice were randomly divided into 3 main groups. The first group (G1); the control group, received only normal saline. The second group (G2); the treated groups, divided into 2 subgroups T1 and T2, This group received melatonin at doses of 10 and 20 mg/kg and intraperitoneal (IP) with gemcitabine at a dose of 50 mg/kg, respectively. The third group (G3); negative control group, divided into 3 subgroups T3, T4 and T5. Subgroup T3, gemcitabine at 50 mg/kg, and T4 and T5, they received melatonin at doses of 10 and 20 mg/kg, intraperitoneally (IP) respectively. The number of mice in each group was 6 mice. The results obtained from the injection of gemcitabine in groups clearly showed the side and cytotoxic effects in the liver tissue that the most lesions were observed in the subgroup (T3). In the groups receiving melatonin, the amount of these lesions was significantly reduced and the reduction of injuries was directly related to the dose of melatonin. The results of this study show that melatonin is effective in reducing the side effects of gemcitabine.

Evaluation of the protective effect of melatonin on histological changes in the liver of adult male rats treated with gemcitabine

Evaluation of the protective effect of melatonin on histological changes in the liver of adult male rats treated with gemcitabine

Protective Effect of Vitamins E & C and Silymarin Against Paracetamol Toxicity on the Liver of Adult male Albino Rat

Protective Effect of Vitamins E & C and Silymarin Against Paracetamol Toxicity on the Liver of Adult male Albino Rat

Protective Effect of Mesenchymal Stem Cells on Methotrexate-Induced Acute Toxicity on Liver of Adult Albino Rats

Protective Effect of Mesenchymal Stem Cells on Methotrexate-Induced Acute Toxicity on Liver of Adult Albino Rats

Ochratoxin A potentiates citrinin accumulation in kidney and liver of rats.

Ochratoxin A (OTA) and citrinin (CTN) are nephrotoxic mycotoxins often found together in grain. The aim of this study was to measure their accumulation in the kidney and liver of adult male Wistar rats, see how it would be affected by combined treatment, and to determine if resveratrol (RSV) would decrease their levels in these organs. The rats received 125 or 250 mg/kg bw of OTA by gavage every day for 21 days and/or 20 mg/kg bw of CTN a day for two days. Two groups of rats treated with OTA+CTN were also receiving 20 mg/kg bw of RSV a day for 21 days. In animals receiving OTA alone, its accumulation in both organs was dose-dependent. OTA+CTN treatment resulted in lower OTA but higher CTN accumulation in both organs at both OTA doses. RSV treatment increased OTA levels in the kidney and liver and decreased CTN levels in the kidney. Our findings point to the competition between CTN and OTA for organic anion transporters 1 and 3.

Atrophic Changes in Hepatocytes by Excess of Garlic Consumption

Background: Garlic (allium sativum) is proved as herbal medicine and is used as self-medication for the control of hypertension, diabetes mellitus and heart diseases. Prolonged usage and high dosage have harmful effects on liver. Aim: To evaluate the injurious effects of garlic (allium sativum) on the liver of adult albino rats. Study design: Experimental study Place and duration of study: Department of Anatomy, Shaikh Zayed Postgraduate Medical Institute, Lahore from 1st October 2013 to 31st March 2014. Methodology: Forty five wistar albino rats of both sexes weighing between 250-350 grams were selected randomly. Two different doses of 500 and 1000 mg/kg of fresh garlic extract were given to the animals by orogastric tube for thirty days. After this period the analysis of quantitative parameters including diameter of hepatic lobule, diameter of the hepatic lobules, diameters of the hepatocytes and their nucleus was then performed on the livers of the sacrificed rats. Results: In the present study, atrophic changes on the size of hepatic lobule, hepatocytes and their nucleus is noted in both experimental group B and C as compared to control group A (P<0.001). Conclusion: It is worth to note that there is a need to evaluate safe dose and to determine the optimal duration of usage of garlic in general public due to its harmful effects on liver. Keywords: Garlic (allium sativum), liver, atrophy, albino rats

Histobiochemical changes in early postmortem interval in liver, pancreas, skin and kidney of adult male albino rats

Histobiochemical changes in early postmortem interval in liver, pancreas, skin and kidney of adult male albino rats

Pathophysiological effects\xa0of Tamiflu on liver and kidneys of male rats

BackgroundTamiflu/oseltamivir phosphate (OP), an anti-influenza drug, has a highly doubted safety especially after many cases of abnormal behaviour and deaths reported after being used. Such controversy was also locally and globally generated, especially after being heavily used in COVID-19 treatment protocol. This study was designed to evaluate the effect of three different doses of OP on the liver and kidneys of male adult albino rats through histological approaches, measuring their DNA integrity and biochemical analyses. Different doses of Tamiflu applied to humans were converted to rats, then observed their effects on the liver and kidneys. Rats were divided into four groups. G1: considered as control group. The rest of the three treated groups were received the same calculated dose of Tamiflu (6.75 mg/kg b.w.) in three different durations. G2, G3 and G4 represented the animals orally received OP, in which the rats received OP twice for 5 consecutive days, once for 10 and 45 days, respectively.ResultsOur data showed numerous deleterious necrotic and fibrotic histopathological changes in the liver, and kidneys; as well as necrotic DNA smears, by using electrophoresis, in OP-treated rats of G2 and G4. In addition, OP significantly increased the serum cellular hepatic/renal toxicity markers (ALT, AST, ALP, GGT, indirect bilirubin, urea, creatinine, uric acid, & Na+). Also, it showed a reduction in the levels of serum total protein, albumin and K+ ions in rats of G2 and G4 compared with G1. In G3, OP treatment did not significantly alter hepatic/renal histological, DNA integrity and biochemical analyses in rats. ConclusionsThe therapeutic and long-term prophylactic doses of OP most likely cause structural and functional hepato- and nephrotoxicity in experimentally subjected rats. So, caution must be taken during Tamiflu treatment, and not used for long durations and/or with repetitive doses (time- and/or accumulative-dose-dependent); especially with patients suffer from liver and/or kidney dysfunction, while the short-term prophylactic dose of OP appears to be relatively safe and could be explored for oral medications.Graphical

High-fat diet intake ameliorates the expression of hedgehog signaling pathway in adult rat liver.

Disproportionate fatty diet intake provokes hepatic lipid accumulation that causes non-alcoholic fatty liver disease, triggering the embryonically conserved Hedgehog (Hh) pathway in the adult liver. The present study incorporates exploring the impact of chronically administered unsaturated (D-1) and saturated (D-2) fat-enriched diets on hematological parameters, liver functioning, and lipid profile in the rat model. Besides, hepatohistology and real time gene expression analysis of Hh signaling pathway genes i.e., Shh, Ihh, Hhip, Ptch1, Smo, Gli1, Gli2, and Gli3 were carried out. Fifteen Rattus norvegicus (♂) of 200 ± 25g weight were grouped into control, D-1, and D-2. Animals were fed on their respective diets for 16weeks. Fatty diet intake resulted in neutropenia, lymphocytosis, monocytosis, polycythemia, and macrocytosis in both experimental groups. Altered liver injury biomarkers, hypertriglyceridemia, and significantly increased very-low-density lipoprotein VLDL were also noted in both high-fat diet (HFD) groups as compared to control. Hepatohistological examination showed disrupted microarchitecture, infiltration of inflammatory cells, cellular necrosis, widened sinusoidal spaces, and microvesicular steatotic hepatocytes in D-1 and D-2. Collagen deposition in both HFD groups marks the extent of fibrosis. Significant upregulation of hedgehog pathway genes was found in fatty diet groups. In comparison with the control group, Shh Ihh, Hhip, Ptch1, Smo, Gli1, Gli2, and Gli3 were upregulated in D-1. In D-2 Shh, Hhip, and Smo expressions were upregulated, Ihh exhibited downregulation as compared to control. Excess fat deposits in liver due to chronic consumption of high-fat diet results in anomalous architecture and functioning. High-fat diet induced significant variations in Hh pathway genes expression; especially Shh, Ihh, Hhip, Ptch1, Smo, Gli1, Gli2, and Gli3 were upregulated. Infiltration of inflammatory cells ( ), widened sinusoidal spaces (▲), cellular necrosis, and micro vesicular steatotic hepatocytes (*) were shown in the liver. Significant collagen deposition in both HFD groups i.e. D-1 and D-2 confirmed liver fibrosis. Excessive intake of dietary fats impaired normal liver functioning and liver inflammation triggered Hh signaling in adult rats.

Histological and Hematoloical Assessment of the Effect of Heinsia crinata Extract on Dichlorvos (DDVP) Induced Toxicity in Adult Wistar Rats

The aim of this study was to assess the “histological and hematological effect of heinsia crinata extract on Dichlorvos (DDVP) Induced Toxicity on liver of adult wistar rats,Thirty (30) adult male Wistar rats were randomly assigned into five groups with group A being the control. Each group contained 6 rats which was given food and water alongside the administration for a period of 21 days which was done orally after acclimatization. Group B was administered orally 35mg//kg DDVP only, group C was administered 35mg/kg DDVP and 500mg/kg Heinsia crinita extract, group D was administered 35mg/kg DDVP and 250mg/kg Heinsia crinita while group E was administered Heinsia crinita extract only. All rats were sacrificed at the end of the 21days and blood was collected by cardiac puncture for hematological analysis and their Livers harvest, processed and stained with Hematoxylin and Eosin for Histopathological studies. Result show PCV showed no significant change in group B, & E (P > 0.05) and was significantly changed in group D (P < 0.05) compared to the control. Hb values showed no significant change amongst the groups (P > 0.05) as compared to the control. No significant changes were observed for WBC in group C, D & E (P > 0.05) as compared to the control but group B was significantly changed (P < 0.05). MCH did not show any significant change across the groups as compared to the control however MCV and MCHC had a significant change in group D while MCHC also had a significant change in group C. Histologically Dichlorvos induce hepatoxicity and inflammation of liver, characterized by the presence of Kupffer's cells, congestion, necrosis and fatty infiltration. It also show that Heinsia crinata has no effect on Dichlorvos induced toxicity.

Impact of Glyphosate Exposure on Glycogen Metabolic Enzymes in the Liver of Adult Male Rats

Background: Glyphosate is a broad spectrum herbicide and desiccant. Diabetes is a group of metabolic diseases resulting due to deficiency in insulin secretion. Chronic hyperglycemia will lead to long term damage and failure of different organs like eyes, kidneys, nerves etc. Liver is the major site for gluconeogenesis and a lot of glycolytic enzymes will be involved. Expression of Glycogen synthase and glycogen phosphorylase, the glycolytic enzymes are studied in this research.
 Aim: To determine whether glyphosate exposure is detrimental to the glycogen metabolic enzymes (Glycogen synthase and phosphorylase) in the liver of adult male rats.
 Materials and Methods: The following study was done on albino rats of wistar strain, and was approved by the institutional animal ethics committee. They were fed with a rat pellet diet. In our study the rats were divided into 4 groups with 6 rats in each and were subjected to glyphosate orally with different dosage in each group and mRNA expression analysis of glycogen related enzymes was done after a span of 16 weeks. The data were analyzed statistically by a one way analysis of variance (ANOVA) followed by Duncan’s multiple range test was used to see the statistical significance among the group. The results with p<0.05 level were considered to be statistically significant.
 Results: The present result showed that the mRNA expression of glycogen synthase significantly reduced (P<0.05) and mRNA expression of glycogen phosphorylase activity increased significantly with an increased dose of glyphosate (P<0.05) to that of control.
 Conclusion: Exposure to glyphosate causes detrimental changes in the glycolytic enzymes glycogen synthase and glycogen phosphorylase leading to diabetes.

Fructose-Rich Diet Attenuates Stress-Induced Metabolic Disturbances in the Liver of Adult Female Rats

BackgroundBoth fructose consumption and chronic stress contribute to the development of metabolic disorders. The consequences of such combination are not fully understood. ObjectiveWe investigated whether fructose supplementation and chronic stress synergistically disturb hepatic lipid and glucose metabolism. The role of energy sensing, redox, and inflammatory status during development of metabolic disturbances was investigated. MethodsFemale Wistar rats, aged 2.5 mo, were divided into 4 experimental groups: control (C) fed a standard diet (commercial food and drinking water); fructose (F) fed the same food and 10% fructose solution; stress (S) fed the standard diet and subjected to chronic unpredictable stress and, stress + fructose (SF) combining conditions F and S as above. Stress included daily stressors: cold water forced swimming, physical restraint, cold room, wet bedding, rocking, switching, or tilting cages. After 9 wk, hepatic enzymes and transcription factors involved in gluconeogenesis, lipogenesis, fatty acid oxidation, antioxidative defence, energy sensing, and cytokines were assessed by qPCR, Western blotting, and spectrophotometry and analyzed by 2-factor ANOVA. ResultsFructose increased AMP-activated protein kinase (AMPK) phosphorylation (40%; P < 0.05) and the ratio of inhibitory phosphorylation to total acetyl-CoA carboxylase (46%; P < 0.01), and decreased sterol regulatory element binding protein 1c nuclear translocation by 30% (P < 0.05) in F and SF compared with C rats. Increased phosPck (phoenolpyruvate carboxykinase) (85%) and G6pase(glucose-6-phosphatase) (55%) was observed in S rats (P < 0.05). A 40% decrease in Apob (apolipoprotein B-100) and an increase in hepatic lipids (P < 0.05), together with a double increase in TNF-α (P < 0.001), were observed in S rats, but without liver histopathological changes. These stress effects on lipid accumulation and TNF-α were abolished in SF rats (P < 0.05). ConclusionsFructose does not enhance stress effects on hepatic lipid and glucose metabolism but attenuates its effects on hepatic lipid accumulation and inflammation, suggesting that, in female rats, AMPK activation prevails over stress-induced effects.

Functional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation.

Background. Liver transplantation remains the only viable therapy for liver failure but has a severely restricted utility. Here, we aimed to decellularize rat livers to form acellular 3D bio-scaffolds suitable for seeding with induced pluripotent cells (iPSCs) as a tool to investigate the role of Wnt/β-catenin signaling in liver development and generation. Methods. Dissected rat livers were randomly divided into three groups: I (control); II (decellularized scaffolds) and III (recellularized scaffolds). Liver decellularization was established via an adapted perfusion procedure and assessed through the measurement of extracellular matrix (ECM) proteins and DNA content. Liver recellularization was assessed through histological examination and measurement of transcript levels of Wnt/β-catenin pathway, hepatogenesis, liver-specific microRNAs and growth factors essential for liver development. Adult rat liver decellularization was confirmed by the maintenance of ECM proteins and persistence of growth factors essential for liver regeneration. Results. iPSCs seeded rat decellularized livers displayed upregulated transcript expression of Wnt/β-catenin pathway-related, growth factors, and liver specification genes. Further, recellularized livers displayed restored liver-specific functions including albumin secretion and urea synthesis. Conclusion. This establishes proof-of-principle for the generation of three-dimensional liver organ scaffolds as grafts and functional re-establishment.