Degeneration Of Hepatocytes Research Articles

"Polyethylene Terephthalate Nanoplastics Caused Hepatotoxicity in Mice Can be Prevented by Betaine: Molecular and Immunohistochemical Insights".

Polyethylene terephthalate nanoplastics (PET-NPs) are one of the most frequently distributed nanoplastics in daily life. Betaine is thought to be a promising hepatoprotective agent. The current investigation focused on whether orally administered PET-NPs caused hepatotoxicity and ameliorative effect of betaine. Forty adult male Swiss albino mice were randomly split into four groups: group I control, group II betaine (1000 mg/kg I/P), group III PET-NPs (200 mg/kg orally), and group IV betaine plus PET-NPs at doses similar to group II& III respectively. After 30 days, blood sample were collected then animals were euthanized and liver specimens were dissected out for biochemical and histopathological examination. PET-NPs induced a significant elevation in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA), as well as an increase in the inflammatory genes a proto-oncogene (c-FOS) and cyclooxygenase 2 (COX2) (p ≤ 0.05), with a substantial decrease in glutathione (GSH) (p ≤ 0.05). Furthermore, on the level of histopathological analysis PET-NPs caused alterations in hepatic tissue architecture as vascular dilatation and congestion with hepatocytes degeneration, bile duct epithelial hyperplasia and inflammatory cell infiltrations While on the level of immunohistochemistry, PET-NPs trigger positive tumor necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-ҠB) expression in comparison to control. Meanwhile, betaine treatment reduced the deleterious effects of PET-NPs. To summarize, PET-NPs may cause hepatotoxicity in mice, with a belief that betaine could mitigate the detrimental impact.

Comparative Effects of Crocin and Losartan on RAGE, TGF-β, TNF-α Gene Expression and Histopathological Changes of the Liver Tissue in Rats With Diabetes.

AGEs, via RAGE, increase the development of hyperglycemia-induced liver damage, and blocking this axis is associated with a reduction in liver disease progression. The goal of this study was to determine how crocin and losartan influenced RAGE, TNF-α and TGF-β gene expression in diabetic rats, as well as histological changes in liver tissue. Diabetes was induced in 40 male Wistar rats using Streptozotocin (50 mg/kg, IP). There were five groups of rats: diabetic and healthy groups, diabetic rats given crocin (50 mg/kg), losartan (25 mg/kg) and both (crocin + Los). Serum glucose, ALT and AST levels were measured 4 weeks later. qPCR was used to examine the TNF-α, TGF-β and RAGE gene expression in liver tissue. Crocin was found to be effective in lowering FBG in the diabetes group. The serum levels of ALT and AST decreased in all treated groups, but this decrease was significant in the crocin + Los group (p < 0.05). The relative expression of RAGE, TNF-α and TGF-β genes was significantly higher in the diabetes group compared to the healthy group. The expression of these genes decreased in groups treated with crocin and Losartan compared to the diabetes group. The highest reduction in RAGE and TGF-β gene expression was reported in those treated with crocin + Los. Histopathology results showed that the diabetes group had more bile ducts and necrosis than the healthy control group, which had no tissue changes. Hepatocyte degeneration, bile duct proliferation, inflammatory changes and hepatocyte necrosis were mild in the treated groups, but no hepatocyte necrosis was observed in the crocin + Los group. Crocin may be a feasible therapeutic agent for treating diabetes and its symptoms when combined with pharmaceutical medications. Human research is still needed to reach clear conclusions.

Optimizing selenium-enriched yeast supplementation in laying hens: Enhancing egg quality, selenium concentration in eggs, antioxidant defense, and liver health

This study evaluated the effects of selenium-enriched yeast (SY) supplementation at various levels on health and production parameters in laying hens, including egg production, egg quality, selenium (Se) concentrations in eggs, liver health, serum biochemical markers, antioxidant function, and immune responses. A total of 360 Hy-Line Brown hens (28 weeks old) were randomly assigned to four dietary groups with six replicates of 15 birds each, monitored over a 12-week feeding trial after a two-week acclimatization period. The dietary groups included a control (basal diet without selenium) and three SY-supplemented groups with Se levels of 0.3 mg/kg (SY03), 1.5 mg/kg (SY15), and 6.0 mg/kg (SY60). The results showed no significant effects of dietary SY on laying performance or feed efficiency (P > 0.05). However, the SY15 group showed significant improvements in egg quality, particularly in albumen height, Haugh Unit and yolk color (P < 0.05). Selenium concentrations in eggs, albumen, and yolk increased dose-dependently, with significant differences in the SY-supplemented groups (P < 0.001). Increased activities of liver enzymes including alanine transaminase, alkaline phosphatase, and aspartate transaminase, alongside elevated levels of uric acid were notable in the SY60 group (P < 0.05). In addition, histological analysis revealed significant hepatocyte degeneration and a higher liver organ index (P < 0.05), in the SY60 group. All of which suggests potential liver toxicity at higher selenium levels. Antioxidant capacity of the birds were significantly enhanced due to dietary supplementation of SY as indicated by increased serum levels of total antioxidant capacity, and activities of catalase, glutathione peroxidase, and superoxide dismutase (P < 0.05). Analysis of hepatic genes expression revealed that SY15 supplementation significantly upregulated key antioxidant-related genes (Nrf2, HO-1, CAT, and NQO1) and downregulated Keap1 expression (P < 0.05), suggesting strong activation of the antioxidant defense system. In conclusion, SY supplementation at 1.5 mg/kg improved egg quality, increased Se concentrations in eggs, and enhanced antioxidant capacity without affecting laying performance or liver health. This makes it a balanced approach to improving egg quality and poultry health. However, higher supplementation levels (6.0 mg/kg) resulted in liver damage, underscoring the importance of careful dosage consideration.

Chronic hyperglycemia induces hepatocyte pyroptosis via Gα12/Gα13-associated endoplasmic reticulum stress: Effect of pharmacological intervention

AimsHyperglycemia induces pathophysiological changes. Endoplasmic reticulum (ER) stress with Gα12 overexpression may promote hepatocyte death. This study investigated whether sustained hyperglycemia triggers ER stress-associated pyroptosis and fibrosis in the liver alongside an overexpression of Gα12, and examined the potential link with VEGF-A levels. Main methodsMice were subjected to a high-fat diet (60 kcal% fat) with streptozotocin (50 mg/kg body weight, three consecutive times, between 12‐13th weeks). AZ2 (a functional Gα12 inhibitor) was treated at 10 mg/kg body weight (5 times/week, 3 weeks). Immunoblotting and immunohistochemistry analyses were performed. Key findingsHepatic Gα12/Gα13 were overexpressed in the diabetic mice. The following proteins downstream from the Gα12 axis were upregulated: PGC1α, PPARα, and SIRT1. Sustained hyperglycemia promoted ER stress marker levels. Histopathological and biochemical assays showed large-sized lipid droplet accumulation, hepatocyte degeneration, and damage as blood transaminase activities increased. Moreover, the diabetic condition increased IL-1β, caspase-1, and NLRP3 levels, which were supportive of pyroptosis. Consistently, the intensities of Masson's trichrome, collagen-1A1, α-SMA, vimentin, and fibronectin all increased. VEGF-A and VEGFR2 levels also increased in the liver and/or sera. The levels of hepatic pigment epithelial-derived factor (PEDF), a physiological antagonist of VEGF-A, decreased with its reciprocal increase in serum. These events were reversed by AZ2 treatment, supporting the role of Gα12 in hyperglycemic stress in the liver. SignificanceChronic hyperglycemia causes hepatic pyroptosis and fibrosis related to ER stress with Gα12/Gα13 and VEGF overexpression, which may be overcome by AZ2 treatments.

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.

Optimization, characterization and biosafety of carotenoids produced from whey using Micrococcus luteus

This study aimed to optimize the production of carotenoid pigments from Micrococcus luteus (ATCC 9341) through the statistical screening of media components and the characterization of antimicrobial, antioxidant, cytogenetic and cytotoxic activities. A BOX-Behnken design was used to assess the effects of whey concentration, inoculum size, pH, temperature, and agitation speed on carotenoid yield. The optimum combination increased production to 2.19 g/L, with a productivity of 0.045 g L-1 h−1 and a productivity yield of 0.644 g/g, as confirmed by an observed carotene production of 2.19 g/L. The final response surface model fitting the data had an R2 of 0.9461. High-performance liquid chromatography (HPLC) analysis identified 12 carotenoid pigment compounds produced by M. luteus. The extracts displayed moderate antimicrobial efficacy against Gram-positive bacteria such as Bacillus cereus (ATCC 11778), Staphylococcus aureus (ATCC 6538), and E. faecalis (ATCC 19433), with inhibition zone diameters (IZD) of 29.0, 14.0, and 37.0 mm, respectively, at 1000 μg/mL. However, its effectiveness against Gram-negative bacteria is limited. In comparison, tetracycline exhibited greater antimicrobial potency. The IC50 value of carotenoids was used to indicate the antioxidant activity. IC50 value from the DPPH assay was 152.80 mg/100mL. An IC50 cytotoxicity value greater than 300 μg/mL was found against normal mouse liver cells, with over 68% cell viability even at 300 μg/mL, indicating low toxicity. Histological structure studies revealed normal myocardial muscle tissue, lung tissue, and kidney tissue sections, whereas liver tissue sections revealed ballooning degeneration of hepatocytes and disorganization of hepatic cords. Cytogenetic parameters revealed that the carotene treatment group had a mitotic index (70%) lower than that of the control but higher than that of the positive control, mitomycin, and did not substantially increase numerical (1.2%) or structural aberrations compared with those of the control, suggesting a lack of genotoxic effects under the experimental conditions. In conclusion, optimized culture conditions enhanced carotenoid yields from M. luteus, and the extracts displayed promising bioactivity as moderate antibiotics against certain gram-positive bacteria and as antioxidants. The high IC50 values demonstrate biosafety. Overall, this bioprocess for enhanced carotenoid production coupled with bioactivity profiling and low cytotoxicity support the application of M. luteus carotenoids.

The protective effects of selenium and boron on cyclophosphamide-induced hepatic oxidative stress, inflammation, and apoptosis in rats

Cyclophosphamide (CP) is an alkylating anticancer drug with broad clinical application that is highly effective in the treatment of cancer and non-malignant diseases. However, the main limiting effect of CP is multi-organ toxicity due to damage to normal tissues. The aim of this study is to compare the hepatoprotective potential of selenium (Se) and boron (B) in CP-induced liver injury in experimental rats. The rats were randomly divided into six equal groups: Control (saline), 200 mg/kg CP (administered once on the fourth day of the experiment), 1.5 mg/kg Se (administered once/time daily for 6 days), 20 mg/kg B (administered once/time daily for 6 days), Se + CP and B + CP administered intraperitoneally (i.p.). Administration of CP leads to an increase in the levels of apoptotic markers (Bax, caspase-3), the apoptotic signaling pathway (Nrf2), oxidative stress indicators (TOS, OSI), lipid peroxidation markers (MPO, MDA), inflammation levels (NF-kB, TNF-α, IL-1β, IL -6), liver function markers (ALT, AST, ALP), while apoptosis markers (Bcl-2), apoptosis pathway (Keap-1), oxidative stress indicator (TAS), inflammation (IL -10) and intracellular antioxidant defense system (SOD, CAT, GPx and GSH) decreased. In addition, degeneration of hepatocytes and congestion in the central veins were observed. In contrast, in the groups administered Se and B with CP, the changes that occurred were reversed. However, it was found that Se protects the liver slightly better against CP damage than B. The protective effect of Se and B against the toxic effects of CP on the antioxidant markers SOD, CAT and GPx1 was also investigated in silico. The in silico results were consistent with the in vivo results for SOD and CAT, but not for GPx1.

Targeting Oxidative Stress: The Potential of Vitamin C in Protecting against Liver Damage after Electron Beam Therapy.

Background: Radiation-induced liver disease (RILD) is a severe complication arising from radiotherapy, particularly when treating abdominal malignancies such as hepatocellular carcinoma. The liver's critical role in systemic metabolism and its proximity to other abdominal organs make it highly susceptible to radiation-induced damage. This vulnerability significantly limits the maximum safe therapeutic dose of radiation, thereby constraining the overall efficacy of radiotherapy. Among the various modalities, electron beam therapy has gained attention due to its ability to precisely target tumors while minimizing exposure to surrounding healthy tissues. However, despite its advantages, the long-term impacts of electron beam exposure on liver tissue remain inadequately understood, particularly concerning chronic injury and fibrosis driven by sustained oxidative stress. Objectives: to investigate the molecular and cellular mechanisms underlying the radioprotective effects of vitamin C in a model of radiation-induced liver disease. Methods: Male Wistar rats (n = 120) were randomly assigned to four groups: control, fractionated local electron irradiation (30 Gy), pre-treatment with vitamin C before irradiation, and vitamin C alone. The study evaluated the effects of electron beam radiation and vitamin C on liver tissue through a comprehensive approach, including biochemical analysis of serum enzymes (ALT, AST, ALP, and bilirubin), cytokine levels (IL-1β, IL-6, IL-10, and TNF-α), and oxidative stress markers (MDA and SOD). Histological and morphometric analyses were conducted on liver tissue samples collected at 7, 30, 60, and 90 days, which involved standard staining techniques and advanced imaging, including light and electron microscopy. Gene expression of Bax, Bcl-2, and caspase-3 was analyzed using real-time PCR. Results: The present study demonstrated that fractional local electron irradiation led to significant reductions in body weight and liver mass, as well as marked increases in biochemical markers of liver damage (ALT, AST, ALP, and bilirubin), inflammatory cytokines (IL-1β, IL-6, and TNF-α), and oxidative stress markers (MDA) in the irradiated group. These changes were accompanied by substantial histopathological alterations, including hepatocyte degeneration, fibrosis, and disrupted microvascular circulation. Pre-treatment with vitamin C partially mitigated these effects, reducing the severity of the liver damage, oxidative stress, and inflammation, and preserving a more favorable balance between hepatocyte proliferation and apoptosis. Overall, the results highlight the potential protective role of vitamin C in reducing radiation-induced liver injury, although the long-term benefits require further investigation. Conclusions: The present study highlights vitamin C's potential as a radioprotective agent against electron beam-induced liver damage. It effectively reduced oxidative stress, apoptosis, and inflammation, particularly in preventing the progression of radiation-induced liver fibrosis. These findings suggest that vitamin C could enhance radiotherapy outcomes by minimizing liver damage, warranting further exploration into its broader clinical applications.

Changes Caused in Liver Parameters in Swiss Albino Mice by Food Colourant (Allura Red) and Preservative (Sodium Benzoate)

Food additives are chemicals that are purposefully added to food to improve its quality. The most widely used food additives in the food industry, pharmacy and cosmetics field are Allura red (a food colour) and sodium benzoate (a food preservative), both of which are employed for various functions such as colouring and preserving. In this study, liver parameters were examined in Swiss male mice after 30, 45 and 60 days of treatment with synthetic Allura red colour and sodium benzoate preservative. Seventy-two male Swiss albino mice (25-30 gm) were divided into four groups with 6 mice per group for each autopsy interval. The first group was control-treated (water), the second group was Allura red treated (172.2 mg/kg body weight), the third group was sodium benzoate treated group (123 mg/kg body weight) and the fourth group was Allura red + sodiumbenzoate treated (86.1 mg/kg + 61.5 mg/kg body weight) for 30, 45 and 60 days. Mice were sacrificed after the 31st, 46th and 61st day and blood samples were taken for serological tests to study SGPT, SGOT, ALP, total protein and serum albumin. The liver was also removed for histological studies of control, sodium benzoate, Allura red and combination groups. The data obtained reveals a noticeable significant increase in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein and albumin in treated mice as compared to control groups. The microscopic study of the liver showed the effect of all dose treatments on the structure of liver cells. It caused fatty degeneration of hepatocytes, congestion of the central vein and necrosis. In conclusion, it was clear that the administration of Allura red, sodium benzoate, and combination dose (AR+SB) in mice caused changes in liver parameters.

Dietary supplementation of poly-dihydromyricetin-fused zinc nanoparticles alleviates fatty liver hemorrhagic syndrome by improving antioxidant capacity, intestinal health and lipid metabolism of laying hens

Fatty liver hemorrhagic syndrome is the main cause of noninfectious death of laying hens and results in substantial economic losses to the poultry industry. This study focused on evaluating the effects of Poly-dihydromyricetin-fused zinc nanoparticles (PDMY-Zn NPs) on antioxidant capacity, liver lipid metabolism, and intestinal health in laying hens. A total of 288 Jingfen laying hens (52 wk old) with similar body weights were randomly divided into 4 dietary groups with 6 replicates in each group for 8 wk. The control group received a basal diet, while the treatment groups were supplemented with PDMY-Zn NPs at levels of 200, 400, and 600 mg/kg, respectively. The results indicate that PDMY-Zn NPs supplementation can enhance antioxidant parameters (P < 0.05) in the blood and liver of laying hens. Simultaneously, it can mitigate vacuolar degeneration and inflammatory necrosis in hepatocytes, improve the relative expression level of related parameters associated with liver lipid metabolism and key regulatory genes (P < 0.05). Furthermore, it has been observed to reshape the composition and diversity of cecum microbes by increasing beneficial probiotics such as Lactobacillus and Prevotella, while also enhancing villi height and villi/crypt ratio in the duodenum and ileum (P < 0.05). Additionally, it elevates liver bile acid content along with the relative expression of key genes involved in liver synthesis (P < 0.05). In summary, PDMY-Zn NPs showed potential to alleviate fatty liver hemorrhagic syndrome by enhancing antioxidant capacity, regulating liver lipid metabolism, and maintaining intestinal health.

Echinacoside Alleviates Carbon Tetrachloride-Induced Chronic Liver Injury by Modulating the NF-κB/NLRP3 Inflammasome Pathway.

The purpose of this study was to investigate the protective effect of echinacoside (Ech) on carbon tetrachloride (CCL4)-induced chronic liver injury in rats and its potential mechanisms. Thirty Sprague-Dawley (SD) rats were randomly divided into five groups: the Control group, the CCL4 group, the CCL4 + Ech 25 mg/kg group, the CCL4 + Ech 50 mg/kg group, and the CCL4 + Ech 100 mg/kg group. The rats were injected intraperitoneally with CCL4 solution twice a week to induce chronic liver injury, and Ech intervention lasted for 4 weeks. After the intervention, the liver and blood samples from rats were collected for subsequent analysis. Ech effectively reduced the levels of serum liver injury markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, alkaline phosphatase, and total bilirubin), attenuated the hepatocyte degeneration and necrosis, improved the severity of liver fibrosis, and inhibited the local inflammatory response of the liver in a dose-dependent manner. Ech effectively mitigated CCL4-induced chronic liver injury in rats by downregulating the NF-κB/NLRP3 inflammasome pathway.

Effects of the Aquatic Extract of Cinnamon Zeylanicum on STZ-Induced Diabetic Rats: A Molecular and Histopathological Study

Background: The prevalence of diabetes mellitus has increased over the past few decades, making it a significant public health challenge of the twenty-first century. Cinnamon, as a traditional medicine, has been used in several regions of the world for its anti-diabetic properties. Objectives: The current study was conducted to determine the effect of Cinnamon Zeylanicum extract on blood glucose levels, oxidative stress markers, and antioxidant enzyme gene expression in diabetic rats. Methods: Forty Sprague-Dawley rats were divided into four groups, each containing 10 rats. A single dose of streptozotocin (50 mg/kg, IP) was used to induce diabetes. In this investigation, 40 mg/kg body weight of cinnamon extract was administered orally. After eight weeks, the levels of glucose, malondialdehyde (MDA), and reduced glutathione (GSH) were determined using biochemical methods. Additionally, the expression levels of catalase and glutathione reductase in the rat liver homogenate were evaluated using real-time PCR. The effect of cinnamon extract on histopathological changes in the rats' liver was also investigated. Results: The findings indicated that the administration of cinnamon extract resulted in a considerable reduction in blood glucose (210 ± 29.9 vs. 449 ± 48.4 mg/dL; P &lt; 0.001) and liver MDA levels (2.01 ± 0.35 vs. 3.05 ± 0.47; P &lt; 0.001) in diabetic rats after eight weeks. However, this extract had no significant effect on GSH levels (4.71 ± 0.25 vs. 4.75 ± 0.42; P = 0.79) in diabetic rats compared to diabetic control rats. The mRNA expression of catalase and glutathione reductase genes in the liver of diabetic control rats (0.73 ± 0.23 and 0.90 ± 0.18, respectively) was significantly lower than that of the healthy control group (1.33 ± 0.37 and 1.46 ± 0.54, respectively) (P = 0.001, P = 0.012). Administration of cinnamon extract increased the expression levels of these antioxidant enzyme genes, but these changes were statistically not significant (P = 0.72 and P = 0.48, respectively). Furthermore, the creation of hyperglycemia led to slight hypertrophic degeneration and lymphocyte infiltration in hepatocytes. Notably, the administration of cinnamon extract was unable to reverse these abnormalities. Conclusions: The findings of our study support cinnamon's anti-diabetic and antioxidant properties in diabetic rats. However, the histological abnormalities in the diabetic rats' livers could not be altered by the administration of cinnamon.

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.

Exploring the combined therapeutic efficacy of bexarotene and icariin in type 2 diabetic rats.

The aim of this study was to determine the single and combined antidiabetic activity and side effects of the retinoid X receptor agonist bexarotene and the thioredoxin-interacting protein inhibitor and peroxisome proliferator-activated receptor γ and AMP-activated protein kinase activator icariin. The rats were grouped as healthy (control), diabetes, diabetes + bexarotene (20 mg/kg), diabetes + icariin (60 mg/kg), diabetes + bexarotene (10 mg/kg) + icariin (30 mg/kg) low-dose combination and diabetes + bexarotene (20 mg/kg) + icariin (60 mg/kg) high-dose combination groups. Icariin treatment led to a significant reduction in glucose levels compared with the diabetes control group, a remarkable outcome observed 45 days after the initial application. HbA1c levels of the icariin and low-dose combination treatment groups were significantly lower than in the diabetes group. Notably, icariin treatment also significantly elevated HOMA-β levels, which is indicative of improved β-cell function. Icariin significantly decreased glucose levels at 30 and 120 min in the oral glucose tolerance test. Moreover, it ameliorated hepatocyte degeneration, hepatic cord dissociation, congestion, mononuclear cell infiltration in the liver, and degeneration in the pancreas. Icariin treatment exhibited robust antidiabetic effects with fewer side effects than other treatment options in this study. In future studies, long-term and varying doses of icariin will contribute to the development of novel antidiabetic drugs.

Anti-diabetic activity of aqueous extract of Trichilia prieureana A. Juss leaves in fructose-fed streptozotocin-induced diabetic male Wistar rats

Background and aimEthanolic extract of Trichilia prieureana leaves have been reported to exhibit anti-hyperglycemic activities without detailed information on the anti-diabetic activities. This study investigated the anti-diabetic activity of aqueous extract of T. prieureana leaves (AETPL) in type 2 diabetic (T2DM) male rats. Experimental procedureT2DM rats (induced with 10 % fructose solution ad libitum for 2 weeks and streptozotocin [STZ]; 40 mg/kg body weight {BW}) in groups B, C, D, E, and F were also administered distilled water (DW), metformin (100 mg/kg BW), 11.2, 22.3, and 44.6 mg/kg BW of AETPL, respectively, whilst non-diabetic rats in Group A received DW only (Sham Control, SC) for 14 days. The T2DM-related parameters were then evaluated. ResultsThe fructose-fed streptozotocin-(FSTZ) treatment related significant (p < 0.05) increases in FBS, HbA1c, fructosamine, HOMA-IR, G6P, GP, TC, TG, LDL-C, urea, bilirubin, hepatic and pancreatic MDA levels; decreases in BW, serum insulin, creatinine, albumin, HOMA-β, glycogen, G6PD, HK, HDL-C, hepatic and pancreatic SOD, GPX, RG, catalase, Hb, PCV, MCH, MCHC, MCV, RBC, WBC, differentials and the destruction of the pancreatic β-cells, hepatocyte degeneration, and central hepatic vein congestion were reversed by AETPL, to values that compared well with SC in most cases. In the IpGGT model, the intraperitoneally administered AETPL reduced the blood glucose and elevated the plasma insulin levels. The AETPL at 44.6 mg/kg BW exhibited the most pronounced effects. ConclusionAETPL (44.6 mg/kg BW) restored T2DM-glycemic control and associated biochemical changes via up-regulation of insulin, carbohydrate metabolizing enzymes and restoration of pancreatic and hepatic histoarchitecture.

The Possible Protective Role of Resveratrol against Zinc Oxide Nanoparticles Induced Hepatic Tissue Injury in Adult Albino Rat

Abstract Background Zinc oxide nanoparticles (ZnO NPs) are widely used in industries and medications. This may elevate the probability of their existence in the environment, which may have harmful side effects on different body organs, especially on the liver. So it became mandatory to search for natural hepatoprotective elements such as Resveratrol. Aim of the Work The aim of the present work was to determine the effect of zinc oxide nanoparticles on the histological structure and biochemical markers of the liver of adult male albino rats and to evaluate the possible protective role of Resveratrol. Material and Methods 40 adult male albino rats aged 3-6 months, were divided randomly into four groups; Group I (Control group), which consisted of 10 male albino rats with free access to food (rat chew) and water; Group II (ZnO NPs group), which included 10 male albino rats, which received a dose of 50 mg/kg body weight ZnO NPs through oral gavage daily for 4 weeks; Group III (Resveratrol group) was composed of 10 male albino rats which received a dose of 20 mg/kg body weight Resveratrol through oral gavage daily for 4 weeks, and Group IV (ZnO NPs + Resveratrol group) included 10 male albino rats which were co-administered with a combination of ZnO NPs at a dose of 50mg/kg body weight and Resveratrol at a dose of 20 mg/kg body weight dose through oral gavage daily for 4 weeks. At the end of the experiment, blood samples were collected for serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). All the animals were sacrificed, and the liver was extracted and processed into paraffin blocks for light microscopic examination. A morphometric study and a statistical analysis were done. Results The present work demonstrated that liver sections obtained from adult male albino rats that received ZnO NPs showed disorganized hepatic architecture, severe affection of the hepatocytes, which had small darkly stained nuclei, and deep acidophilic cytoplasm. The hepatocytes sometimes showed extensive cytoplasmic vacuolations. Most hepatocytes had small apoptotic nuclei and were surrounded by clear halos. While some hepatocytes lost their cell boundaries and coalesced together. Central veins were dilated, distorted, and congested with areas of epithelial lining detachment. Most of the blood sinusoids appeared congested with marked inflammatory cell infiltration. The portal tracts showed vascular congestion, dilatation, and proliferation of the bile ducts. There was a marked increase in the collagen deposition around the portal tracts, central veins, and in-between hepatocytes. Marked depletion of glycogen content with sporadic positive PAS reactions within the cytoplasm of the hepatocytes was also noticed. Hepatocyte apoptosis was evident by a significant increase in caspase-3 expression compared to the control group. On the other hand, ZnO NP +Resveratrol group showed the restoration of normal hepatic lobules with few areas of subcapsular haemorrhage. Most hepatocytes appeared polygonal in shape, with acidophilic cytoplasm and central rounded vesicular nuclei. While few hepatocytes appeared degenerated with dark stained pyknotic nuclei and cytoplasm showed hydropic degeneration. Most of the blood sinusoids returned to their normal sizes with flattened endothelial cells. However, sometimes they were congested, dilated, and contained Kupffer cells. Some central veins appeared congested. The portal tract also returned to its normal size with a marked decrease in inflammatory cell infiltration and showed apparent minimal collagen fiber deposition. Another finding in the present work was that Resveratrol restored the glycogen content of the hepatocytes which were depleted in ZnO NPs group. This was marked by a strong PAS positive reaction in the cytoplasm of most hepatocytes, with few hepatocytes with weak PAS reaction. Resveratrol co-treatment with ZnO NPs significantly reduced the degeneration and necrosis of hepatocytes. This was evident in our study by the apparent negative Caspase-3 reaction in the cytoplasm of most hepatocytes. Clear deterioration of liver function tests was observed in ZnO NPs group compared with the control, with marked improvement in the group treated with ZnO NPs and Resveratrol together. Conclusion The present study demonstrated the degenerative and hepatotoxic effects of ZnO NPs on the histological structure and function of the liver and the hepatoprotective role of Resveratrol against these effects.

Incidence and pathological effects during encysted progenetic Euclinostomum heterostomum metacercariae infection in the freshwater fish spotted snakehead (Channa punctatus)

Aim: To assess the incidence and pathological effects during encysted progenetic Euclinostomum heterostomum metacercariae infestation in the freshwater fish spotted snakehead (Channa punctatus). Methodology: Samples of Channa punctatus were collected from Tilaiya Reservoir, Koderma, Jharkhand, India, during pre-monsoon, monsoon, and post-monsoon seasons. The encysted metacercariae trematodes were isolated from Channa punctatus. Characterization was performed based on the morphology and sequencing analysis of a partial 18S rRNA gene. Further, the kidney and liver samples from infected fish were subjected to histopathological studies. Prevalence, abundance, and Intensity of infection were further determined. Results: Morphological identification suggests that the encysted metacercariae belonged to Digenean trematodes of genera Euclinostomum, and amplification of partial sequence of 18S rRNA, and phylogenetic analysis revealed the isolated metacercariae were Euclinostomum heterostomum. The histopathological study of the kidney showed hepatocyte degeneration, cytoplasmic vacuolation, and nuclear transformations. Liver fibrosis was observed in Channa punctatus. The prevalence during pre-monsoon, monsoon, and post-monsoon season ranged from 66.1% to 81.1%, abundance from 0.74 to 0.92, and intensity ranged from 1 to 1.14 using the Margolis formula. Interpretation: The study highlights the infestation of Euclinostomum heterostomum in Channa punctatus during the pre- monsoon climate appears favorable for the abundance of parasites. Hence, a proper inspection before consumption is necessary. Key words: Euclinostomum heterostomum, Infestation, Metacercariae, Parasites, Progenetic infection

Pathological and biochemical investigation of the effects of Silybum marianum against Methomyl damage in broiler liver

This study was aimed to investigate the protective/preventive and/or curative effects of Silybum marianum seed powder against Methomyl toxication by examining some biochemical parameters and pathological changes hepatic in broiler chicks fed with feeds supplemented with Methomyl and S. marianum seed powder. For this purpose, 4 different groups, each containing 32 animals, were used; Control group (CONT), Methomyl group (MET), S. marianum seed powder group (SMT) and Methomyl + S. marianum seed powder group (MET+SMT). In the study, Methomyl was added to the feeds as 20 ppm and S. marianum seed powder as 10 g·kg-1. The trial period was planned as 28 days, and necropsies of animals from each group were performed daily, and samples were taken for histopathology and biochemistry. In the study, liver enzyme activities and liver tissue oxidative stress markers GPx, MDA and SOD values were found to be similar in the CONT and SMT groups, but statistically higher in the MET group. In the MET+SMT group, the increased parameters were lower than the MET group. The histopathological examinations of liver sections, hyperemia, hemorrhage, hydropic degeneration and fatty changes of hepatocytes, focal necrosis, dissociation of remark cords, mononuclear cell infiltration in the portal area and bile ducts hyperplasia were detected. It has been observed that S. marianum given for preventive/healing purposes reduces histopathological damage and contributes positively in all groups. It has been concluded that S. marianum can be added to poultry diets against Methomyl residues or contamınatıons according to thıs study.

Preventing High Fat Diet-Induced Obesity and Related Hepatic Steatosis by Chlorin e6-Mediated Photodynamic Therapy.

Obesity and its associated hepatic steatosis have become a global concern, posing numerous health hazards. Photodynamic therapy (PDT) is a unique approach that promotes anti-obesity by releasing intracellular fat. Chlorin e6 (Ce6)-PDT was tested for its anti-obesity properties in male ovariectomized (OVX) beagle dogs, as well as male C57BL/6 and Balb/c mice. The 12 OVX beagles were randomly assigned to one of four groups: high-fat diet (HFD) only, Ce6 only, Ce6 + 10 min of light-emitting diode light (LED) treatment, and Ce6 + 15 min of light treatment. We assessed several parameters, such as body weight, adipose tissue morphology, serum biochemistry, and body fat content analysis by computed tomography (CT) scan in HFD-fed beagle dogs. At the end of the study period, dogs that were treated for 35 days with Ce6 and exposed to LED irradiation (660 nm) either for 10 min (Ce6 + 10 min of light) or for 15 min (Ce6 + 15 min of light) had decreased body weight, including visceral and subcutaneous fats, lower aspartate transaminase (AST)/alanine transaminase (ALT) ratios, and a reduction in the area of individual adipocytes with a concomitant increase in the number of adipocytes. Furthermore, C57BL/6 male mice following an HFD diet were effectively treated by Ce6-PDT treatment through a reduction in weight gain and fat accumulation. Meanwhile, Ce6-PDT attenuated hepatocyte steatosis by decreasing the epididymal adipose tissue and balloon degeneration in hepatocytes in HFD-fed Balb/c mice. Taken together, our results support the idea that Ce6-PDT is a promising therapeutic strategy for the recovery of obesity and obesity-related hepatic steatosis.

Cardiometabolic risk factors in MASLD patients with HCC: the other side of the coin

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) constitutes the commonest cause of chronic liver disorder worldwide, whereby affecting around one third of the global population. This clinical condition may evolve into Metabolic Dysfunction-Associated Steatohepatitis (MASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC), in a predisposed subgroup of patients. The complex pathogenesis of MASLD is severely entangled with obesity, dyslipidemia and type 2 diabetes (T2D), so far so nutritional and lifestyle recommendations may be crucial in influencing the risk of HCC and modifying its prognosis. However, the causative association between HCC onset and the presence of metabolic comorbidities is not completely clarified. Therefore, the present review aimed to summarize the main literature findings that correlate the presence of inherited or acquired hyperlipidemia and metabolic risk factors with the increased predisposition towards liver cancer in MASLD patients. Here, we gathered the evidence underlining the relationship between circulating/hepatic lipids, cardiovascular events, metabolic comorbidities and hepatocarcinogenesis. In addition, we reported previous studies supporting the impact of triglyceride and/or cholesterol accumulation in generating aberrancies in the intracellular membranes of organelles, oxidative stress, ATP depletion and hepatocyte degeneration, influencing the risk of HCC and its response to therapeutic approaches. Finally, our pursuit was to emphasize the link between HCC and the presence of cardiometabolic abnormalities in our large cohort of histologically-characterized patients affected by MASLD (n=1538), of whom 86 had MASLD-HCC by including unpublished data.