Degeneration Of Hepatocytes Research Articles

Resveratrol Administration Ameliorates Hepatotoxicity in Mercuric Chloride-‎Induced Liver Injury in Rats

Mercuric chloride (HgCl2) pollution and poisoning has been a worldwide health ‎concern for decades, especially after the industrial revolutions. The aim of this study ‎was to investigate the role of resveratrol in reversing the deleterious effects of ‎HgCl2 exposure to resume the normal functions of hepatocyte. To achieve the study, ‎mature Sprague Dawley rats were assigned to five groups. Negative control group ‎‎(C) kept without any treatment; vehicle-treated group (D) received dimethyl ‎sulfoxide (DMSO); resveratrol-treated group (R), received 100 mg/kg of resveratrol; ‎HgCl2-intoxicated group (HD), received i.p. injection of HgCl2 at a dose of 1 mg/kg ‎for 30 consecutive days along to oral gavage of DMSO; and finally HgCl2-‎intoxicated group treated with resveratrol (HR) as same treatment strategy of R-‎group. At the endpoint of the experiment, blood samples were collected for ‎biochemical liver function tests along with serum concentrations of ‎malondialdehyde (MDA), glutathione (GSH), body weight, as well as ‎histopathological investigation was done too. Study results revealed a significant ‎‎(P<0.05) elevation in serum AST, ALP, GGT, and MDA in HD group in comparison ‎with HR group. However, resveratrol treatment has led to a significant (P<0.05) ‎increase in serum levels of GSH in HR group in comparison with the HD group. ‎Histopathological sections showed vacuolar degeneration in HD hepatocytes while ‎resveratrol treatment protected the hepatocytes against the chemical injury. ‎Altogether, It is concluded that resveratrol administration has the ability to increase ‎the resistance of liver against the HgCl2-induced hepatotoxicity via increase the ‎antioxidant yields such as GSH resulted in reduction of hepatocellular texture ‎damage.

New insight into PAH4 induced hepatotoxicity and the dose-response assessment in rats model

PAH4 (sum of benzo[a]pyrene, chrysene, benz[a]anthracene and benzo[b]fluoranthene) has been proposed as better marker than benzo[a]pyrene to assess total PAHs exposure in foodstuffs. However, the toxicological behaviors of PAH4 combined exposure remain unclear. This study aimed to investigate PAH4 toxicity effects with non-targeted metabolomics approach and evaluate the external and internal dose-response relationships based on benchmark dose (BMD) analysis. Male Sprague-Dawley rats were treated by gavage with vehicle (corn oil) or four doses of PAH4 (10, 50, 250, 1000 μg/kg·bw) for consecutive 30 days. After the final dose, the liver, blood and urine samples of rats were subsequently collected for testing. The concentrations of urinary mono-hydroxylated PAHs metabolites (OH-PAHs) including 3-hydroxybenzo[a]pyrene (3-OHB[a]P), 3-hydroxychrysene (3-OHCHR) and 3-hydroxybenz[a]anthracene (3-OHB[a]A) were determined to reflect internal PAH4 exposure. Our results showed PAH4 exposure increased relative liver weight and serum aspartate aminotransferase (AST) activity and caused hepatocyte swelling and degeneration, implying hepatotoxicity induced by PAH4. Serum metabolomics suggested PAH4 exposure perturbed lipid metabolism through upregulating the expression of glycerolipids metabolites, which was evidenced by markedly increased serum triglyceride (TG) level and hepatic TG content. Additionally, urinary OH-PAHs concentrations presented strong positive correlations with the external dose, indicating they were able to reflect PAH4 exposure. Furthermore, PAH4 exposure led to a dose-response increase of hepatic TG content, based on which the 95% lower confidence value of BMDs for external and internal doses were estimated as 5.45 μg/kg·bw and 0.11 μmol/mol·Cr, respectively. In conclusion, this study suggested PAH4 exposure could induce hepatotoxicity and lipid metabolism disorder, evaluating the involved dose-response relationships and providing a basis for the risk assessment of PAHs.

Immunohistochemical Alterations of Syndecan-1 in Sheep Liver with Cystic Echinococcosis

Cystic echinococcosis is formed by the larval forms of Echinococcus granulosus, causes health problems in humans and different species of animals worldwide. There is still limited information about the pathophysiological response to cystic echinococcosis in the liver. Syndecan-1 (Sdc1) is a cell surface proteoglycan of the liver. It has a crucial role in the pathophysiology of various liver diseases. This study aimed to investigate the immunohistochemical expression of Sdc1 in the liver with cystic echinococcosis in sheep. A total number of 51 liver tissue samples with cystic echinococcosis and ten healthy livers were examined. The tissue samples were stained with hematoxylin-eosin (HE) for histopathological examinations. Sdc1 was determined in the same liver tissues by immunohistochemistry. Infected liver tissues mainly showed severe inflammatory reactions, congestion, diffuse degeneration, and necrosis of hepatocytes around the cysts. The results indicated severe Sdc1-positive staining in hepatocytes around the cysts. Liver tissues of the control group showed relatively mild immunopositive reactions. This study determined that the Sdc1 significantly increased in the sheep livers with cystic echinococcosis infection.

Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms.

Diabetes is a ubiquitous disease that causes several complications. It is associated with insulin resistance, which affects the metabolism of proteins, carbohydrates, and fats and triggers liver diseases such as fatty liver disease, steatohepatitis, fibrosis, and cirrhosis. Despite the effectiveness of Sitagliptin (ST) as an antidiabetic drug, its role in diabetes-induced liver injury is yet to be fully investigated. Therefore, this study aims to investigate the effect of ST on hepatic oxidative injury, inflammation, apoptosis, and the mTOR/NF-κB/NLRP3 signaling pathway in streptozotocin (STZ)-induced liver injury. Rats were allocated into four groups: two nondiabetic groups, control rats and ST rats (100 mg/kg), and two diabetic groups induced by STZ, and they received either normal saline or ST for 90 days. Diabetic rats showed significant hyperglycemia, hyperlipidemia, and elevation in liver enzymes. After STZ induction, the results revealed remarkable increases in hepatic oxidative stress, inflammation, and hepatocyte degeneration. In addition, STZ upregulated the immunoreactivity of NF-κB/p65, NLRP3, and mTOR but downregulated IKB-α in liver tissue. The use of ST mitigated metabolic and hepatic changes induced by STZ; it also reduced oxidative stress, inflammation, and hepatocyte degeneration. The normal expression of NF-κB/p65, NLRP3, mTOR, and IKB-α were restored with ST treatment. Based on that, our study revealed for the first time the hepatoprotective effect of ST that is mediated by controlling inflammation, oxidative stress, and mTOR/NF-κB/NLRP3 signaling.

The role of melatonin in preventing amiodarone-induced rat liver damage.

Long-term exposure to amiodarone, an antiarrhythmic drug, can induce different organ damage, including liver. Cell damage included by amiodarone is a consequence of mitochondrial damage, reactive oxygen species production, and cell energy depletion leading to programmed cell death. In the present study, hepatoprotective potential of neurohormone melatonin (50mg/kg/day) was evaluated in a chronic experimental model of liver damage induced by a 4-week application of amiodarone (70mg/kg/day). The obtained results indicate that amiodarone induces an increase in xanthine oxidase activity, as well as the content of the lipid and protein oxidatively modified products and p53 levels. Microscopic analysis further corroborated the biochemical findings revealing hepatocyte degeneration, apoptosis, and occasional necrosis, with the activation of Kupffer cells. Coadministration of melatonin and amiodaron prevented an increase in certain damage associated parameters, due to its multiple targets. In conclusion, the application of melatonin together with amiodarone prevented an increase in tissue oxidative damage parameters and moderately prevented liver cell apoptosis, indicating that the damage of hepatocytes provoked by amiodarone supersedes the protective properties of melatonin in a given dose.

Effects of Gardenia Ternifolia Leaf Extract on antioxidant and hepatic enzymes in sniper-induced toxicity in Albino rats

Aim: This study evaluates the effects of Gardenia ternifolia leaf extract on antioxidant and hepatic enzymes in sniper-induced toxicity in albino rats. Methodology: A total of 42 male albino rats weighing 120g to 150g, grouped into 6 groups of 7rats each. Group 1 (Negative control), Group 2 (Positive control), Group 3 (Therapeutic Low Dose), Group 4 (Therapeutic High Dose), Group 5 (Prophylactic Low Dose) and Group 6 (Prophylactic High Dose). After 4 weeks of treatment, the rats were anaesthetized, sacrificed and blood samples collected. The Liver was also harvested for histological analysis. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) were estimated using a rat-specific sandwich-enzyme linked immunosorbent assay (ELISA) method. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were carried out using Reitman Frankel method. Alkaline phosphatase (ALP) was carried out using colorimetric phenolphthalein method. The liver tissue was prepared and stained using standard Haematoxylin and Eosin (H & E) staining technique and captured using scope TekTM device. Results: The mean SOD and GPx values for the therapeutic and prophylactic groups were significantly higher (P <.05) when compared with the positive control. The mean SOD and GPx values in the therapeutic groups were not significantly different (P >.05) from the negative control. The mean ALT, AST and ALP values for the therapeutic and prophylactic groups were significantly lower (P <.05) than the positive control but significantly higher (P <.05) than the negative control. Histology analysis of liver indicated normal histoarchitecture in the negative control while in the positive control, there were severe cell degeneration, distortion, necrosis and death of the hepatocytes. The Therapeutic Low Dose and Prophylactic Low Dose groups indicated severe degeneration and hypertrophy of hepatocytes. The Therapeutic High Dose and Prophylactic High Dose groups showed less deposit, well delineated radiating hepatocytes and near normal cytoarchitecture. Conclusion: Administration of Sniper® (dichlorvos) led to an increase in oxidative stress; depletion of antioxidant enzyme levels. It elevated liver enzymes levels, caused histopathological changes and death of cells in the liver. The treatment with leaf extract of Gardenia ternifolia ameliorated the effect of dichlorvos toxicity, restored the anti-oxidant and liver enzyme levels especially the high dose extract.

The Biochemistry and Pathology Characteristics of Coronavirus Disease 2019

Coronavirus Disease 2019 started appeared in December 2019 China’s, Hubei Province, Wuhan. During the following three months, it spread rapidly to numerous provinces in China and transversely the world. The initial bunch was epidemiologically associated with a seafood wholesale market in Wuhan. Many essential aspects of the pathogenesis, pathology, and pathophysiology of SARS- CoV2 have not yet clear. Here, we offer a comprehensive overview of the biochemistry Characteristics and histopathological results present in various organs and cells and the pathophysiology. In this review we found many damage in some organic system, such as pulmonary edema with hyaline membrane formation, desquamation and hyperplasia of pneumocytes, proteinaceous in Respiratory tract, spleen atrophic, degeneration and focal necrosis of hepatocytes, Esophageal, stomach and bowel in digestive tract. Degenerated or necrosed myocardial cells in Heart. Degeneration and shedding of renal tubules epithelial cells, hyaline casts in Kidneys and other organs.

Effects of fullerene C60 on liver tissue in liver ischemia reperfusion injury in rats undergoing sevoflurane anesthesia

ABSTRACT This study aimed to investigate the effects of fullerene C60 on rat liver tissue in a liver ischemia reperfusion injury (IRI) model under sevoflurane anesthesia to evaluate the ability of nanoparticles to prevent hepatic complications. A total of 36 adult female Wistar Albino rats were divided into six groups, each containing six groups as follows: sham group (Group S), fullerene C60 group (Group FC60), ischemia-reperfusion group (Group IR), ischemia-reperfusion-sevoflurane group (Group IR-Sevo), ischemia-reperfusion-fullerene C60 group (Group IR-FC60), and ischemia-reperfusion-fullerene C60-sevoflurane group (Group IR-FC60-Sevo). Fullerene C60 100 mg/kg was administered to IR-FC60 and IR-FC60-Sevo groups. In the IR group, 2 h of ischemia and 2 h of reperfusion were performed. At the end of reperfusion, liver tissues were removed for biochemical assays and histopathological examinations. Hepatocyte degeneration, sinusoidal dilatation, prenecrotic cells, and mononuclear cell infiltration in the parenchyma were significantly higher in Group IR than in all other groups. Thiobarbituric acid reactive substances levels were significantly higher in Group IR than in the other groups, and the lowest thiobarbituric acid reactive substances level was in Group IR-FC60 than in the other groups, except for Groups S and FC60. Catalase and Glutathione-S-transferase activities were reduced in the IR group compared to all other groups. Fullerene C60 had protective effects against liver IR injury in rats under sevoflurane anesthesia. The use of fullerene C60 could reduce the adverse effects of IRI and the associated costs of liver transplantation surgery.

Reduced liver damage and fibrosis with combined SCD Probiotics and intermittent fasting in aged rat.

This study aimed to examine the impact of SCD Probiotics supplementation on liver biomolecule content and histological changes during a 30-day intermittent fasting (IF) program in 24-month-old male Sprague-Dawley rats. Rats underwent 18-h daily fasting and received 1 × 108 CFU of SCD Probiotics daily. Liver tissue biomolecules were analysed using FTIR Spectroscopy, LDA, and SVM techniques, while histopathological evaluations used Haematoxylin and eosin and Masson trichrome-stained tissues. Blood samples were collected for biochemical analysis. Gross alterations in the quantity of biomolecules were observed with individual or combined treatments. LDA and SVM analyses demonstrated a high accuracy in differentiating control and treated groups. The combination treatments led to the most significant reduction in cholesterol ester (1740 cm-1 ) and improved protein phosphorylation (A1239 /A2955 and A1080 /A1545 ) and carbonylation (A1740 /A1545 ). Individually, IF and SCD Probiotics were more effective in enhancing membrane dynamics (Bw2922 /Bw2955 ). In treated groups, histological evaluations showed decreased hepatocyte degeneration, lymphocyticinfiltration, steatosis and fibrosis. Serum ALP, LDH and albumin levels significantly increased in the SCD Probiotics and combined treatment groups. This study offers valuable insights into the potential mechanisms behind the beneficial effects of IF and SCD Probiotics on liver biomolecule content, contributing to the development of personalized nutrition and health strategies.

Multi-omics reveals aging-related pathway in natural aging mouse liver

Aging is associated with gradual changes in liver structure, altered metabolites and other physiological/pathological functions in hepatic cells. However, its characterized phenotypes based on altered metabolites and the underlying biological mechanism are unclear. Advancements in high-throughput omics technology provide new opportunities to understand the pathological process of aging. Here, in our present study, both metabolomics and phosphoproteomics were applied to identify the altered metabolites and phosphorylated proteins in liver of young (the WTY group) and naturally aged (the WTA group) mice, to find novel biomarkers and pathways, and uncover the biological mechanism. Analysis showed that the body weights, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased in the WTA group. The grips decreased with age, while the triglyceride (TG) and cholesterol (TC) did not change significantly. The increase of fibrosis, accumulation of inflammatory cells, hepatocytes degeneration, the deposition of lipid droplets and glycogen, the damaged mitochondria, and deduction of endoplasmic reticulum were observed in the aging liver under optical and electron microscopes. In addition, a network of metabolites and phosphorylated proteomes of the aging liver was established. Metabolomics detected 970 metabolites in the positive ion mode and 778 metabolites in the negative ion mode. A total of 150 pathways were pooled. Phosphoproteomics identified 2618 proteins which contained 16621 phosphosites. A total of 164 pathways were detected. 65 common pathways were detected in two omics. Phosphorylated protein heat shock protein HSP 90-alpha (HSP90A) and v-raf murine viral oncogene homolog B1(BRAF), related to cancer pathway, were significantly upregulated in aged mice liver. Western blot verified that protein expression of MEK and ERK, downstream of BRAF pathway were elevated in the liver of aging mice. However, the protein expression of BRAF was not a significant difference. Overall, these findings revealed a close link between aging and cancer and contributed to our understanding of the multi-omics changes in natural aging.

The effect of Abrus cantoniensis Hance on liver damage in mice

The liver is a well-known organ contributing to digestion, hemostasis and detoxification, while liver injury is a world-widely distributed health problem with limited treatment choices. We detected the protective effect of Abrus cantoniensis Hance (ACH) on Carbon tetrachloride-induced (CCl4) liver injury in mice. Fifty ICR (Institute of Cancer Research) animals were grouped into five groups of control (a), CCl4 (d), ACH (25 mg/kg) treated group (c), ACH (50 mg/kg) treated group (b), and ACH (100 mg/kg) treated group (e). Mice in groups d, c, b, and e were given CCl4 every four days, and treated animals received daily ACH supplementation. The results showed that the daily body weights in CCl4-induced animals were slightly lower; however, the weight of ACH-treated mice increased, particularly in the higher dose group. Treatment with CCl4 led to increased liver weight and liver indices in mice, whereas supplementation with ACH reduced both liver weights and liver indices in animals. Histo-pathological analysis indicated that CCl4 led to inflammatory cell infiltration and hepatocellular degeneration, with collagenous fibers proliferation in ICR animals. In contrast, supplementation with ACH prominently decreased inflammatory cells and degeneration of hepatocytes and inhibited collagen fiber hyperplasia. Furthermore, the levels or concentrations of AST (p < 0.0001), ALT (p < 0.0001), MDA (p < 0.0001), IL-1β (p < 0.01), TNF-α (p < 0.01) and IL-6 (p < 0.01) were significantly higher in CCl4 induced ICR animals in group d. However, mice treated with ACH showed lower levels or concentrations of those indices in dose dependent manner. The levels of GSH-px (p < 0.0001), CAT (p < 0.0001) and SOD (p < 0.0001) were significantly reduced in CCl4 group; however, all these three enzymes exhibited significant (p < 0.05) increase in animals supplemented with ACH in dose dependent manner. The microbiome sequencing generated 1,168,327 filtered reads in the mice samples. A notable difference was observed in the composition of 6 phyla and 37 genera among the five ICR animal groups. Supplementation with ACH increased the abundance of beneficial genera of Coprococcus, Blautia and Clostridium, while concurrently decreased the presence of pathogenic genera of Mycoplasma and Helicobacter. In conclusion, we revealed that Abrus cantoniensis Hance has the potential to relieve liver damage induced by CCl4, through the reduction of inflammation, enhancement of antioxidant capacity, and regulation of intestinal microbiota.

FRI573 Liver Enzyme Elevation In A Patient With Grave’s Disease; Could This Be Due To Anti-thyroid Drug Therapy?

Abstract Disclosure: C.S. Park: None. J.L. Gilden: None. Introduction: Abnormal liver enzymes (LFTs) are often observed in patients with both hypothyroidism, as well as in 2.5% of patients with Grave’ s (GRAVES) Hyperthyroidism (HTH) treated with anti-thyroid medications (ATD). Furthermore, abnormal Liver function tests are reported within 6 months of untreated thyrotoxicosis in 39% of patients. The other common causes of abnormal LFTs in HTH are congestive hepatopathy with thyrotoxic heart failure, previous underlying liver disease, hypermetabolism of hepatocytes due to HTH with subsequent anoxia and free radical damage, hepatocyte degeneration due to glycogen and protein decomposition acceleration, and autoimmune-related liver injury. Case: A 52-year-old Mexican American female, with allergies, and recent COVID vaccine, was referred to the endocrine clinic for an unknown duration of GRAVES with unintentional weight loss and occasional tremors of three months duration, and some leg weakness, but denied other symptoms of hyperthyroidism, gastrointestinal disorders, or other autoimmune disorders. There was no known family history of HTH, or other autoimmune disorders. She presented after initiation of methimazole (MMI) 5 mg twice daily, prescribed by her primary care provider. VS BP 137/70 HR 94 BMI 25.32. Exam-slight tremor on outstretched arms, no ophthalmopathy, 35-40 gm thyromegaly, no onycholysis or pretibial myxedema. Labs: TSH &amp;lt;0.010 (0.27-4.20 mIU/mL); Free T4 1.84 (0.5-1.6 ng/dL); T3 Free 5.31 (2.52-4.34 pg/mL); TG AB 100 (0-4 IU/mL); Thyroid Peroxidase 1,425.00 (0.00-9.00 iu/Ml); TSI 27.10 (&amp;lt;=0.54 iu/l). LFT’s were elevated (AST 105, repeat 53, (13-39 U/L);ALT 272,repeat 150 (7-52U/L); Alkaline Phosphatase (AP) 305,repeat 290 (34-104 U/L); T.Bilirubin 0.4 (0.0-1.0 mg/dL)]. AP Bone 159 (0-55 U/L) AP liver 195 (0-94 U/L). ANA was positive with SCL-70 autoantibodies 5.0 (&amp;lt;1.0 AI). Thyroid US: slightly heterogenous thyroid gland of chronic thyroiditis. RUQ abdominal US-normal. MMI was stopped for 2 weeks, then restarted. 1 week later-TSH &amp;lt;0.10 uIu/mL, Free T4 1.79 ng/dL, Free T3 5.91 pg/mL and LFT’s improved over the next several weeks (AST 39 U/L; ALT 85 U/L; Alkaline Phosphatase 220 U/L. SCL-70 remained positive, and she remained asymptomatic. Conclusion: Although the etiology for LFT elevation is suggestive of MMI treatment, since it occurred with the initiation and titration of this therapy, this patient also had markedly elevated SCL-70, seen in 20% of patients with systemic sclerosis, which can also be associated with lupus erythematosus, and primary biliary cirrhosis. Furthermore, the elevation continued, even after MMI had been stopped and then when restarted, was lower. This case demonstrates that it is crucial to evaluate for other etiologies of elevated LFTS in any patient with HTH, and not just assume that it is due to GRAVES or ATD, and also to consider the possibility of other autoimmune conditions. Presentation: Friday, June 16, 2023

Baseline and recurrent exposure to the standard dose of artemisinin-based combination therapies (ACTs) induces oxidative stress and liver damage in mice (BALB/c)

BackgroundIn malaria-endemic countries, repeated intake of artemisinin-based combination therapies (ACTs) is rampant and driven by drug resistance, improper usage, and easy accessibility. Stress effects and potential liver toxicity due to the frequent therapeutic use of ACTs have not been extensively studied. Here, we investigated the effects of repeated treatment with standard doses of the commonly used ACTs artemether/lumefantrine (A/L) and artesunate-amodiaquine (A/A) on oxidative stress and liver function markers in male mice (BALB/c).MethodsForty Five mice were divided into three groups: control, A/L, and A/A. The drugs were administered three days in a row per week, and the regimen was repeated every two weeks for a total of six cycles. The levels of oxidative stress and liver function markers were measured in both plasma and liver tissue after initial (baseline) and repeated exposures for the second, third, and sixth cycles.ResultsExposure to A/L or A/A caused a significant (p < 0.001) increase in plasma malondialdehyde (MDA) levels after the first and repeated exposure periods. However, Hepatic MDA levels increased significantly (p < 0.01) only after the sixth exposure to A/A. Following either single or repeated exposure to A/L or A/A, plasma and liver glutathione peroxidase (GPx) and catalase (CAT) activities, plasma aspartate and alanine transaminase, alkaline phosphatase activity, and bilirubin levels increased, whereas total plasma protein levels decreased significantly (p < 0.001). Varying degrees of hepatocyte degeneration and blood vessel congestion were observed in liver tissues after a single or repeated treatment period.ConclusionIrrespective of single or repeated exposure to therapeutic doses of A/L or A/A, plasma oxidative stress and liver damage were observed. However, long-term repeated A/A exposure can led to hepatic stress. Compensatory processes involving GPx and CAT activities may help reduce the observed stress.

Comparison of Azithromycin Toxicity in Chickens and Quails

Background: The pharmacologic and toxicological response to different drugs vary according to the type and breed of the animal. Objectives: This investigation was carried out to compare the toxic effects of azithromycin on chickens and quails. Methods: The animals of each kind were divided into 3 groups; the first group served as the control and received just distilled water; the second and third groups received different doses of azithromycin (5% and 10% of the median lethal dose) over 5 days. Results: Compared to quails, the LD50 in chicks was substantially higher. Both chicks and quails treated with high doses of azithromycin showed a substantial difference in neurobehavioral and motor measures. Total antioxidant capacity (TAC) and glutathione decrease in chicks receiving the high dose of azithromycin, whereas, in quail, the prior impact was present in both doses. With the cholinesterase activity in quails and chicks being inhibited, a high dose of azithromycin dramatically raised the level of caspase-3 in the quail. We observed severe diffuse vacuolar degeneration in hepatocytes with infiltration of inflammatory cells in quails and chicks in the high dose and less severe effects in quail and chicks in the lower dose. In quails’ livers, tumor necrosis factor-(TNF)-α was strongly expressed at high and weakly at low doses. Still, in chickens’ livers, TNF-α expression was moderate at high and low at low doses. Conclusion: At the same percentages and dose of the LD50 in both quails and chicks, azithromycin causes severe toxic effects in quails but less toxic effects in chickens.

Effects of Zinc Oxide Nanoparticles on Biochemical Hematological Parameters and Liver Histopathology of Rabbit

Zinc oxide nanoparticles have broad spectrum utilization in the nano-industry because of their distinct characteristics. Increased human exposure to nanoparticles has been observed through various products like dyes, additives, ceramics, beauty products rubber etc. Objectives: This study was carried out to evaluate the ZnO nanoparticle's toxic effects on hematological and biochemical parameters in lower and higher doses in a rabbit model. Methods: Thirty male rabbits were used and ten rabbits were assorted in each group. Groups included control and experimental group 1 (low dose group 50mg/kg) &amp; and group 2 (high dose group 75 mg/kg). The oral administration of ZnO nanoparticles was given for 20 days. The parameters included body weight, blood glucose level, serum level of aspartate transaminase (AST), serum level of alanine transaminase (ALT), serum albumin, total cholesterol, triglycerides, hemoglobin, red blood cells, white blood cells and platelets. The parameters were measured on the 1st, 10th and 20th day of the experiment. Results: Nanoparticle administration resulted in a non-significant decrease in body weight and blood glucose level. Serum level aspartate transaminase in experimental group 2 was significantly increased. Triglycerides had shown a non-significant increase in experimental group 2. Non-significant decrease was observed in red blood cells and platelet count of both the experimental groups. Histopathological studies revealed damaged liver parenchyma and hepatocyte degeneration in the high-dose group. Conclusions: ZnO nanoparticle administration resulted in damage to liver histopathology. Its toxicity resulted in increased levels of triglycerides, AST and ALT due to liver damage.

Effects of repeatedly heated cooking oil consumption in mice: a study on health implications

Background: Cooking oils are a major part of human diets, but repeated use of heated oils can have detrimental effects on consumer health. This study aims to investigate the impact of different heating grades of vegetable oils on the hemato-biochemical parameters and vital organs like the heart, liver, kidney, and intestine in mice. Methods: Thirty mice were randomly assigned to different treatment groups, including a control group (diet only), unheated cooking oil (UHCO) group, single heated cooking oil (SHCO) group, three times repeatedly heated cooking oil (3RHCO) group, and repeatedly heated cooking oil (ReHCO) group. Blood and organ samples were collected on day 31 to investigate hemato-biochemical parameters and histo-morphological alterations in response to the oil treatments. Results: The oil-treated groups showed significant (P&lt;0.05) decreases in the total erythrocyte, leukocyte, and hemoglobin levels. Meanwhile, serum levels of total cholesterol, triglyceride, high-density lipoprotein, glucose, and creatinine increased significantly (P&lt;0.05), while low-density lipoprotein and protein levels dropped markedly in the treatment groups. Severe histo-morphological alterations were also found in the liver (hepatocytic degeneration with hydropic change in the 3RHCO and ReHCO groups), kidney (glomerular atrophy with increased glomerular space, tubular degeneration, and lymphocytic infiltration in the SHCO, 3RHCO, and ReHCO groups), and colon (lymphocytic infiltration in the mucosal layer of ReHCO group). Conclusions: These findings suggest that the consumption of heated oils can have severe adverse effects on consumers' health, leading to alterations in blood chemistry and damage to vital organs.

Metabolomics Analysis and Biochemical Profiling of Arsenic-Induced Metabolic Impairment and Disease Susceptibility.

Our study aimed to conduct a comprehensive biochemical profiling and metabolomics analysis to investigate the effects of arsenic-induced metabolic disorders, with a specific focus on disruptions in lipid metabolism, amino acid metabolism, and carbohydrate metabolism. Additionally, we sought to assess the therapeutic potential of resveratrol (RSV) as a remedy for arsenic-induced diabetes, using metformin (MF) as a standard drug for comparison. We measured the total arsenic content in mouse serum by employing inductively coupled plasma mass spectrometry (ICP-MS) after administering a 50-ppm solution of sodium arsenate (50 mg/L) in purified water. Our findings revealed a substantial increase in total arsenic content in the exposed group, with a mean value of 166.80 ± 8.52 ppb (p < 0.05). Furthermore, we investigated the impact of arsenic exposure on various biomarkers using enzyme-linked immunosorbent assay (ELISA) methods. Arsenic exposed mice exhibited significant hyperglycemia (p < 0.001) and elevated levels of homeostatic model assessment of insulin resistance (HOMA-IR), hemoglobin A1c (Hb1Ac), Inflammatory biomarkers as well as liver and kidney function biomarkers (p < 0.05). Additionally, the levels of crucial enzymes linked to carbohydrate metabolism, including α-glucosidase, hexokinase, and glucose-6-phosphatase (G6PS), and oxidative stress biomarkers, such as levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), were significantly reduced in the arsenic-exposed group compared to the control group (p < 0.05). However, the level of MDA was significantly increased. Molecular analysis of gene expression indicated significant upregulation of key enzymes involved in lipid metabolism, such as carnitine palmitoyl-transferase-I (CPT-I), carnitine palmitoyl-transferase-II (CPT-II), lecithin-cholesterol acyltransferase (LCAT), and others. Additionally, alterations in gene expression related to glucose transporter-2 (GLUT-2), glucose-6-phosphatase (G6PC), and glucokinase (GK), associated with carbohydrate metabolism, were observed. Amino acid analysis revealed significant decreases in nine amino acids in arsenic-exposed mice. Metabolomics analysis identified disruptions in lipid metabolomes, amino acids, and arsenic metabolites, highlighting their involvement in essential metabolic pathways. Histopathological observations revealed significant changes in liver architecture, hepatocyte degeneration, and increased Kupffer cells in the livers of arsenic-exposed mice. In conclusion, these findings enhance our comprehension of the impact of environmental toxins on metabolic health and offer potential avenues for remedies against such disruptions.

Histologic changes in the liver and kidney tissues of rats with acute alcohol injury and metabolic correction

Annotation. The liver and kidneys are among the organs that often suffer from the toxic effects of ethanol. The issue of drug correction of alcoholic organ damage, and in particular the role of H2S, remains insufficiently studied. The aim of the study was to evaluate the role of quercetin, hydrogen sulphide donor NaHS and their combination in the correction of morphological changes in the liver and kidneys of rats with acute alcohol injury (AAI). The study was conducted on 25 white male rats weighing 120-130 g, divided into five groups (5 rats in each group). Animals of groups 2-5 were modelled with AAI by intragastric administration of 40% ethanol at a dose of 20 ml/kg for 7 days. In order to correct the AAI, animals of group 3 were administered quercetin (100 mg/kg, intraperitoneally, once/day, for 7 days), group 4 – the hydrogen sulphide donor NaHS-H2O (3 mg/kg, intraperitoneally, once/day, for 7 days), group 5 – both quercetin and NaHS-H2O in the above doses. Animals of group 1 (control) received an equivalent amount of solvents. Histological examinations were performed according to conventional methods. It has been established that in the liver of rats with AAI there are disturbances in the lobular structure, radial ordering of the hepatic beams, signs of inflammation, hypertrophy and fatty infiltration of hepatocytes. In the kidneys, signs of renal glomerular fragmentation, vascular glomerular compaction, tubular epithelial dystrophy, and inflammation are found. Some improvements in the histological structure of the liver and kidneys were observed with quercetin, but they were inferior to those observed with NaHS. Combined therapy with quercetin and NaHS was most effective in restoring the normal structure of the liver and kidneys of rats: the radial arrangement of hepatic beams was restored, the nuclear cytoplasmic index increased, signs of fatty degeneration of hepatocytes and renal epithelial dystrophy decreased, and the activity of the inflammatory response in the organs decreased. The obtained results histologically confirm the feasibility of using hydrogen sulphide donors to enhance the hepatoprotective and nephroprotective effects of quercetin in the setting of AAI.

Antioxidant and antidiabetic effects of aqueous extract of &lt;i&gt;Senna alata&lt;/i&gt; on alloxan-induced diabetic rats

This study aimed to evaluate the antioxidant effect and the state of the liver following injury by alloxan monohydrate and treatment with an aqueous extract of Senna alata (SA) leaf. A total of 24 male Albino Wistar rats assigned into 4 groups (A-D) of 6 rats per group were used in this study. Forty-eight hours following administration of alloxan monohydrate and confirmation of diabetes mellitus in groups B-D rats, group C were treated with SA while group D rats were treated with glibenclamide. Rats in groups A and B received distilled water. The treatments were through oral administration, once daily for 21 consecutive days. On day 21 post-treatment, serum samples were collected for in vivo antioxidants and liver enzyme assays. The liver tissues were also collected for macroscopic examination and histomorphology. The in vitro antioxidant activity of SA was also determined using DPPH photometric model. The SA-treated rats recorded significantly reduced activities of ALT, ALP and total bilirubin values when compared to rats in the diabetic untreated group. There was also a significant increase in the activities of catalase, superoxide dismutase and glutathione in SA-treated rats compared to those of the untreated diabetic group. The study also recorded 67.33% in vitro antioxidant activity of SA at 400 μg/ml. Liver photomicrographs of rats treated with the extract were comparable to those of the normal control while diabetic untreated rats showed congestion of the central vein, degeneration and necrosis of hepatocytes. SA has both in vitro and in vivo antioxidant activity and protected the liver against damage by alloxan monohydrate.

Reparative and Antioxidant Effects of New Analogues of Immunomodulator Thymogen in Experimental Model of Liver Damage.

We studied the reparative and antioxidant effects of Thymogen and its new structural analogues obtained by binding amino acid D-Ala to the N- or C-end of the peptide molecule in acute toxic hepatopathy. Intragastric administration of carbon tetrachloride for 5 days caused the development of fat degeneration of hepatocytes, a decrease in catalase activity, and an increase in malondialdehyde concentration. Administration of peptides suppressed oxidative peroxidation and stimulated reparative regeneration of hepatocytes; Thymogen analogues produced more pronounced hepatotropic and antioxidant effects than Thymogen. Inclusion of D-Ala enhanced the effect of Thymogen on the processes of regeneration in hepatocytes and the antioxidant effect under conditions of acute carbon tetrachloride hepatopathy. The highest efficiency was achieved when the amino acid was added to the C-end of the molecule.