Hepatic Tissue Research Articles

Synergistic therapeutic effect of Guggul gum resin on antidiabetic activity of saxagliptin

Type 2 Diabetes Mellitus is an endocrine metabolic disorder leading to impaired glucose utilization. This disease is managed by both commercial drugs and herbal products eliciting various interactions. The evaluation of one such interaction between saxagliptin (SAXA, substrate of CYP3A4), and Guggul extract (GE) from Commiphora wightii is done in this present study. The concomitant administration of the SAXA with GE had restored the levels of otherwise increased blood glucose and biochemical parameters and otherwise decreased total glycogen and oxidative stress markers more effectively as compared to the solely consumed SAXA or GE. These results were corroborated by histopathological evaluation where the combination treatment showed better mitigation of hepatic, renal and pancreatic tissue damage that occurred due to induced diabetes. Furthermore, CYP3A11 mRNA (murine homolog to human CYP3A4) expression levels were observed to be reduced to non-diabetic levels in combination therapy which was otherwise unachievable. The molecular docking studies predicted improved interaction between CYP3A4 and bioactive content of GE, i.e., guggulsterone E-Z, possessing binding energy of -9.96 kcal/mol along with SAXA, confirming the co-existence of both the ligands at different binding sites of the metabolizing enzyme. The synergistic interactions of GE and SAXA helped in better restoration of tissue damage and increased CYP3A11 mRNA expression levels caused by induced diabetes.

A 3-Week Ketogenic Diet Increases Skeletal Muscle Insulin Sensitivity in Individuals With Obesity: A Randomized Controlled Crossover Trial.

A ketogenic diet (KD) can induce weight loss and improve glycemic regulation, potentially reducing the risk of developing type 2 diabetes. To elucidate the underlying mechanisms behind these beneficial effects of a KD, we investigated the impact of a KD on organ-specific insulin sensitivity (IS) in skeletal muscle, liver, and adipose tissue. We hypothesized that a KD would increase IS in skeletal muscle. The study included 11 individuals with obesity who underwent a randomized, crossover trial with two three-week interventions: 1) KD and 2) standard diet. Skeletal muscle IS was quantified as the increase in glucose disposal during a hyperinsulinemic-euglycemic clamp (HEC). Hepatic IS and adipose tissue IS were quantified as the relative suppression of endogenous glucose production (EGP) and the relative suppression of palmitate flux during the HEC. The KD led to a 2.2 kg weight loss, increased insulin-stimulated glucose disposal, whereas the relative suppression of EGP during the HEC was similar. In addition, the KD decreased insulin-mediated suppression of lipolysis. In conclusion, a KD increased skeletal muscle IS in individuals with obesity.

A traditional medicinal food <i>Arum rupicola</i> (Kardeh) ameliorates thioacetamide-induced hepatotoxicity in animal model: Role of PCNA/Bax, oxidative stress, and inflammatory cytokines

Nutraceuticals are major contributors to human health because of their modulatory effects on various physiological and pathological processes. Arum rupicola (Kardeh) is a traditional medicinal food used for many gastrointestinal and enzymatic disorders. The present study evaluates the acute toxicity and hepatoprotective effects of methanolic extracts of Arum rupicola (MEAR) in rat with thioacetamide (TAA)-induced liver injury in rat. Thirty Sprague-Dawley rats were divided into five groups: Group A, normal control, and group B, TAA control groups were treated orally with 10% tween 20; group C reference rat received daily of 50 mg/kg silymarin drug; Groups D and E rat received daily doses of 250 mg/kg and 500 mg/kg MEAR, respectively. In addition, group B–E received three injections of 200 mg/kg TAA weekly for 60 days. The safety evaluation of MEAR revealed nontoxic effects at 2,000 and 5,000 mg/kg dosage in rat. TAA inoculation provoked significant hepatotoxic alterations indicated by increased hepatocyte proliferation, endothelial tissue injury, ambiguous nucleus, and elevated cytoplasmic vacuoles. TAA treatment initiated increased inflammatory response and necrosis process in different areas of hepatic tissues. Meanwhile, MEAR treatment showed significant prophylaxis against TAA-induced hepatotoxicity, supported by its suppressing actions on oxidative stress, and apoptotic and inflammatory mediators. MEAR treatment significantly down-regulated proliferating cell nuclear antigen (PCNA) in both liver and spleen parenchymal tissues, lowered pro-apoptotic Bcl-2-associated X (Bax) proteins, reduced inflammatory and redox mediators, lowered transforming growth factor-beta tissue expression and malondialdehyde content, while, increased antioxidants (superoxide dismutase, catalase, and glutathione peroxidase). The outcomes provided significant hepatoprotective potential of MEAR mediated by its modulatory effects on several cellular pathways, making it a viable source of a potent pharmaceutical discovery.

Prenatal stress induces sex- and tissue-specific alterations in insulin pathway of Wistar rats offspring.

Prenatal stress may lead to tissue and sex-specific cardiometabolic disorders in the offspring through imbalances in the insulin signaling pathway. Therefore, we aimed to determine the sex-specific adaptations of prenatal stress on the insulin signaling pathway of cardiac and hepatic tissue of adult offspring Wistar rats. Wistar pregnant rats were divided into control and stress groups. Unpredictable stress protocol was performed from the 14th to the 21st day of pregnancy. After lactation, the dams were euthanized and blood was collected for corticosterone measurement and the offspring were separated into four groups according to sex and intervention (n=8/group). At 90 days old, the offspring were submitted to an oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT). After euthanasia blood collection was used for biochemical analysis and the left ventricle and liver were used for protein expression and histological analysis. Stress increased maternal corticosterone levels, and in the offspring, decreased glucose concentration in both OGTT and ITT, reduced insulin receptor (Irβ) and insulin receptor substrate-1 (IRS1) activation and reduced insulin receptor inhibition (PTP1B) in the liver of male offspring at 90 days old, without repercussions in cardiac tissue. Moreover, female offspring submitted to prenatal stress exhibited reduced fatty acid uptake, with lower hepatic CD36 expression, reduced high density lipoprotein (cHDL) and increased Castelli risk indexes I and II. Unpredictable prenatal stress evoked reduced insulin sensitivity and liver-specific impairment in insulin signaling activation in male while increasing markers of cardiovascular risk in females.

Carbenoxolone upregulates TRAIL\\TRAILR2 expression and enhances the anti-neoplastic effect of doxorubicin in experimentally induced hepatocellular carcinoma in rats

AimsThis study investigates the in vivo anticancer activity of carbenoxolone (CBX) and its role in fighting hepatocellular carcinoma (HCC) progression and alleviating resistance against doxorubicin (DOX). Moreover, the molecular mechanism of action of CBX is explored. MethodsHCC was induced in Sprague Dawley rats via biweekly administration of thioacetamide (TAA) (200 mg/kg) intraperitoneally (i.p.) for 16 weeks after administering a single dose of diethylnitrosamine (DEN) (200 mg/kg, i.p.). A prophylactic model was established by treating rats with i.p. CBX (20 mg/kg/day) for 4 weeks starting on week 13 post-TAA injection. A therapeutic model was established by treating rats with CBX, DOX, or their combination for 7 weeks following 16 weeks of TAA administration. Serum Alpha-fetoprotein (AFP) and biochemical markers of hepatic functions were assessed. Histopathological examinations of hepatic tissues were performed. Immunohistochemical and qRT-PCR analyses were applied to assess the differential expressions of TRAIL/TRAILR2, Bcl-2, TGF-β1, and caspases 3,8, and 9. ResultsCBX markedly improved hepatic functions, reduced serum AFP levels, and alleviated TAA-induced hepatic histopathological alterations. CBX triggered apoptosis as evident by upregulating apoptotic markers: TRAIL/TRAILR2, caspases 3,8, and 9, and downregulating the antiapoptotic protein Bcl-2. CBX downregulated TGF-β1. Interestingly, CBX/DOX combination mitigated hepatic damage and induced apoptosis in a way that surpassed DOX-only treatment. ConclusionThe current study proposes that CBX is a promising anti-tumor compound, which can work effectively under prophylactic and therapeutic modes. Interestingly, CBX enhanced the anti-tumor effect of DOX. CBX exerted these effects via, in part, stimulating TRAIL-induced apoptosis along with attenuating fibrosis.

Alterations of Hepatic Lipidome Occur in a Gouty Model: A Shotgun Lipidomics Study.

Liver injury, such as nonalcoholic fatty liver disease, is a common symptom observed in patients with gout/hyperuricaemia. However, the exact mechanisms are still unclear. There is ongoing controversy about whether representative agents like colchicine and febuxostat, commonly used to manage gout, could also help prevent the liver injury. Liver plays a crucial role in uric acid (UA) production and lipid metabolism. Thus, the study aimed to investigate the aberrant lipid metabolism in the liver during injury and the effects of these drugs. An advanced multi-dimensional mass spectrometry-based shotgun lipidomics technology was employed for class-targeted lipid analysis of cellular lipidomes in hepatic tissue of a gouty model induced by a combination of monosodium urate crystals and high-fat diet with or without treatment with colchicine and febuxostat. Serum UA, blood urea nitrogen, creatinine, proinflammatory cytokines, expression of AMP-activated protein kinase protein, footpad histopathology, and footpad swelling and pain threshold of these mice were assessed to evaluate the progression of gout. Lipidomics analysis clearly demonstrated that the ectopic fat accumulation as well as changes in fatty acyls composition in TAG pool, impaired mitochondrial function resulted by decreased tetra 18:2 cardiolipin, and reduced 4-hydroxyalkenal bioavailability in liver tissue could contribute to liver damage to the gouty model. Treatment with colchicine or febuxostat not only ameliorated gouty symptoms but also corrected these abnormal hepatic lipid metabolism patterns. This study shed light on underlying mechanism(s) for liver injury in gout/hyperuricaemia and suggested that administration of drugs like colchicine and febuxostat could prevent liver injury.

Pre-Clinical Study of Hydro-Ethanol (60:40) Extract of <i>Areca catechu</i> (L.) on Testicular Androgenesis in Albino Rat: An Approach for Herbal Male Contraceptive Development

The present study was designed to determine the anti-testicular activity of hydro-ethanol seed extract of Areca catechu (10, 20 and 40 mg) in dose-dependent fashion in albino rats. Seminal vesicular fructose (SVF), oxidative stress sensors, gene expression, somatic weight, reproductive organo-somatic indices, spermiological, hormonal profile, and testicular histological examination for qualitative and quantitative investigations of spermatogenesis were observed. In compared to the placebo treated control (PTC), the exposure of the said doses showed a statistical significant downward deviation in the spermiological, hormonal, SVF profile, kinetics of testicular key androgenic dehydrogenase enzymes, and diameters of seminiferous tubules. Anti-oxidant enzyme kinetics were reduced significantly against PTC, and the quantity of malondialdehyde in male gonad and sperm precipitate was elevated in significant level (p<0.05). Expression of apoptotic promoting gene in testis was increased (p<0.05) and anti-apoptotic Bcl-2 gene expression exhibited a significant decrease (p<0.05) in treated group comparison to the PTC. The alterations in the activities of phosphatases in hepatic tissue was not significant from the background of PTC suggesting that the plant has no systematic undesirable effect in physiological processes. The observation highlighted that 10 mg dose as the threshold dose for imposition of such anti- testicular activity leading to male contraception.

The cytoplasmic-nuclear transport of DDX3X promotes immune-mediated liver injury in mice regulated by endoplasmic reticulum stress

Immune-mediated liver injury is a common characteristic of various liver diseases, including autoimmune and viral hepatitis. Here, we investigated the role of DEAD-box helicase 3, X-linked (DDX3X) in immune-mediated liver injury. Liver injury was induced in C57BL/6J mice via concanavalin A (Con A). DDX3X hepatocyte-specific knockout (DDX3XΔHep) mice and control (DDX3Xfl/fl) mice were utilized to investigate the role of DDX3X in liver injury. Primary hepatocytes were treated with tunicamycin (TM) to induce ER stress in vitro. The expression of DDX3X in patients with various liver diseases was evaluated. Hepatic DDX3X expression increased, and DDX3X translocated from the cytoplasm to the nucleus during Con A-induced liver injury. DDX3X deficiency ameliorated mouse liver injury and reduced ER stress in liver tissue. The inhibition of ER stress with 4-PBA significantly attenuated liver injury while decreasing DDX3X levels in liver tissue. However, the upregulation of hepatic DDX3X expression reversed Con A-induced liver injury and negated the protective effect of 4-PBA. Mechanistically, the nuclear translocation of DDX3X promoted ER stress-induced apoptosis through the transcriptional induction of CHOP. Moreover, DDX3X was elevated and translocated into the nucleus in patients with HBV-LF and AIH. Additionally, serum DDX3X levels markedly increased in patients with HBV-LF, and a consistent decrease in DDX3X was associated with a good prognosis. The cytoplasmic-to-nuclear translocation of DDX3X promotes ER stress-induced apoptosis, which is an obligatory step that drives hepatic necrosis and tissue damage. Notably, DDX3X is a potential therapeutic target for immune-mediated liver injury.

Hepatotoxicity induced by subacute exposure of Mancozeb and Arsenic in Wistar rats: Mitigating effect of quercetin and catechin

BackgroundWidespread use of Mancozeb (MZ) fungicide in endemic areas having high levels of arsenic (As+3) in the groundwater is likely to cause toxicosis in humans and animals. Therefore, the present study aimed to determine the hepatotoxic effect of MZ and As+3 interaction in Wistar rats and mitigating potential of quercetin and catechin on such toxicity. MethodsSixty adult rats were randomly divided into 10 groups of 6 animals each. Group I served as control and group II was exposed to MZ (800 mg kg-1, PO). Groups III, IV, and V were provided drinking water containing As+3 at the rate of 10, 50 and 100 µg L-1, respectively. Groups VI, VII, and VIII were given drinking water containing As+3 at 10, 50 and 100 µg L-1, respectively, along with MZ. Groups IX and X received drinking water contaminated with 100 µg L-1, As+3 and MZ along with quercetin or catechin (50 mg kg-1 each), respectively. ResultsSignificant (p <0.05) alterations in hepatic biomarkers in blood, liver antioxidant status and hepatic histoarchitecture were observed in animals treated with individual toxicants in a dose-dependent manner, however, such toxicity-induced changes were more severe in co-exposed rats. The administration of quercetin or catechin significantly mitigated the dual toxicant administration-driven changes in biochemical markers of hepatic damage, hepatic antioxidant profile and liver histomorphology. ConclusionsBoth quercetin and catechin proved beneficial in reducing toxicant-induced oxidation-mediated hepatic damage as demonstrated by alleviation in altered levels of determinants of hepatic biochemical and oxidative stress parameters in addition to restoration of toxicant-induced histological alterations of hepatic tissue.

Exploring the hepatoprotective potential of the probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide-postbiotic on ibuprofen-induced acute liver injury in rats.

The present study investigates the hepatoprotective effect of a probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide (EPS) against ibuprofen-induced acute liver injury, and to explore the involved underlying mechanisms. Hepatotoxicity was induced by administration of a single dose of ibuprofen (200 mg/kg body weight). The Lpb. plantarum E1K2R2 (109 CFU) and its EPS (200 mg/kg bw) were separately used to feed rats for seven consecutive days before ibuprofen administration. Liver toxicity was assessed by monitoring levels of serum liver enzymes, liver relative weight, oxidative stress and inflammatory markers, and through histopathological analysis. The results showed that ibuprofen administration significantly increased (P < 0.05) liver relative weight, elevated levels of alanine-amino transferase (ALT), aspartate-amino transferase (AST), decreased hepatic gluthatione (GSH) and endogenous antioxidant enzymes including, superoxide dismutase (SOD), catalase (CAT) and increased malondialdehyde (MDA) levels, nitric oxide (NO) and myeloperoxidase (MPO) in hepatic tissues. However, pre-treatment with Lpb. plantarum E1K2R2 and its EPS significantly attenuated these toxicity manifestations. Both pre-treatments restored liver weight, normalized transaminase enzyme levels, enhanced the activity of liver antioxidant enzymes (SOD and CAT), increased GSH content, and significantly reduced NO, MPO and MDA levels (P < 0.05), indicating their protective role against oxidative stress and inflammatory response induced by ibuprofen. Furthermore, histopathological analysis confirmed regular liver morphology in rats pre-treated with the probiotic and its EPS. These findings highlight the potential effectiveness of the probiotic Lpb. plantarum E1K2R2 and its EPS in mitigating ibuprofen-induced liver toxicity.

The processing mechanism of vinegar-processed Curcumae Rhizome enhances anti hepatic fibrotic effects through regulation of PI3K/Akt/mTOR signaling pathway

BackgroundHepatic fibrosis, a chronic pathological condition resulting from various forms of persistent liver injury, in the later stage, it can evolve into cirrhosis and even liver cancer. Curcumae Rhizoma (CR), traditionally recognized for its properties in line qi break blood, eliminate accumulation and relieve pain. According to traditional Chinese medicine (TCM) principles, vinegar-processing enhances CR's ability to enter the liver meridian and act on the blood level, potentially augmenting its therapeutic effects on hepatic diseases. Therefore, vinegar-processed Curcumae Rhizoma (VCR) is frequently employed in treating liver fibrosis and related hepatic conditions. However, the underlying mechanisms of vinegar processing in enhancing its therapeutic efficacy remain unclear. MethodsThe anti-liver fibrosis effects of CR and VCR were verified at individual and cellular levels. Subsequently, HPLC-Q-TOFMS and pharmacokinetic analysis were utilized to elucidate the potential bioactive substances underlying the enhanced anti-fibrotic efficacy of VCR. Building upon these findings, network pharmacology and metabolomics were integrated to screen for key effect components and regulatory pathways. Finally, the mechanisms of action were further analyzed and validated at the tissue and cellular levels through Western blotting (WB) and molecular docking studies. ResultsBoth CR and VCR exhibited therapeutic effects against hepatic fibrosis, with VCR demonstrating enhanced efficacy after vinegar processing. 6 sesquiterpenes including furanodiene and curdione, showed significant alterations in plasma exposure and hepatic distribution post-processing. VCR significantly improved pathological liver conditions, lipid accumulation, and fibrosis severity. Additionally, VCR markedly reduced the expression of α-SMA in the liver and attenuated the elevations in liver function markers such as ALT and AST. Combined network pharmacology, metabolomics, and hepatic tissue WB analysis revealed that the reduced phosphorylation of the PI3K/Akt/mTOR pathway is a critical mechanism in VCR's anti-fibrotic effects. Experiments on LX-2 cells demonstrated that four sesquiterpenes, including furanodiene and curdione, effectively inhibited the proliferation of activated hepatic stellate cells (HSCs). Furanodiene, in particular, promoted apoptosis in activated HSCs by reducing phosphorylation levels of the PI3K/Akt/mTOR pathway proteins, increasing BAX expression, and activating downstream caspase-3 to achieve the effect of anti-liver fibrosis. ConclusionVinegar-processing significantly increases the plasma exposure and hepatic distribution of components such as furanodiene in VCR, enhancing anti-fibrotic efficacy by downregulating the phosphorylation levels of the PI3K/Akt/mTOR pathway and promoting HSC apoptosis. This study provides a comprehensive explanation of the vinegar-processing mechanism and its role in enhancing the anti-fibrotic effects of VCR, offering insights for its clinical application in liver fibrosis treatment and reference for the mechanistic study of other vinegar-processed herbal medicines.

Evaluation of the hepatoprotective effect of curcumin alone or in combination with vitamin C in methotrexate-induced hepatotoxicity in mice.

To assess the hepatoprotective effect of curcumin and/or vitamin C in methotrexate-induced hepatotoxicity. The experimental study was conducted at the Department of Pharmacology, College of Medicine, and the Iraqi Centre for Cancer and Medical Genetic Research, Mustansiriya University, Baghdad, Iraq, from Nov 12, 2020, to June 1, 2021, and comprised Swiss albino female mice aged 3-4 months and weighing 30-40g each. The mice were divided into 5 groups and treated for 10 days. Group 1 received distilled water, group 2 received single-dose methotrexate on the 10th day of the trial, group 3 was treated with curcumin plus methotrexate, group 4 was treated with vitamin C plus methotrexate, and group 5 was treated with curcumin and vitamin C plus methotrexate. Parameters measured were serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase, as well as hepatic tissue malondialdehyde, superoxide dismutase and glutathione. Data was analysed using SPSS 16. There were 35 mice; 7(20%) in each of the 5 groups. Hepatoprotection produced by curcumin as reflected by a decrease in lactate dehydrogenase and malondialdehyde levels was significant (p<0.05). Vitamin C also produced a significant hepatoprotection, demonstrated by a decrease in alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase and malondialdehyde levels. The combination of curcumin and vitamin C reflected an additive effect demonstrated by a significant decrease in malondialdehyde (p<0.05). Curcumin and/or vitamin C provided hepatoprotection against methotrexate-induced hepatotoxicity through modulation of oxidative stress biomarkers.

Mesenchymal Stem Cell-Derived Exosomes Attenuate Hepatic Steatosis and Insulin Resistance in Diet-Induced Obese Mice by Activating the FGF21-Adiponectin Axis.

Exosomes derived from mesenchymal stem cells have shown promise in treating metabolic disorders, yet their specific mechanisms remain largely unclear. This study investigates the protective effects of exosomes from human umbilical cord Wharton's jelly mesenchymal stem cells (hWJMSCs) against adiposity and insulin resistance in high-fat diet (HFD)-induced obese mice. HFD-fed mice treated with hWJMSC-derived exosomes demonstrated improved gut barrier integrity, which restored immune balance in the liver and adipose tissues by reducing macrophage infiltration and pro-inflammatory cytokine expression. Furthermore, these exosomes normalized lipid metabolism including lipid oxidation and lipogenesis, which alleviate lipotoxicity-induced endoplasmic reticulum (ER) stress, thereby decreasing fat accumulation and chronic tissue inflammation in hepatic and adipose tissues. Notably, hWJMSC-derived exosomes also promoted browning and thermogenic capacity of adipose tissues, which was linked to reduced fibroblast growth factor 21 (FGF21) resistance and increased adiponectin production. This process activated the AMPK-SIRT1-PGC-1α pathway, highlighting the role of the FGF21-adiponectin axis. Our findings elucidate the molecular mechanisms through which hWJMSC-derived exosomes counteract HFD-induced metabolic dysfunctions, supporting their potential as therapeutic agents for metabolic disorders.

Tasar Silkworm Pupae oil: A potential therapeutic and edible lipid source to mitigate the oxidative stress and cholesterol complications associated with diabetes

The anti-oxidant and cholesterol-lowering activity of tasar pupae oil (TPO), loaded with α-linolenic acid in streptozotocin-induced diabetic Wistar rats was studied. The suitability of TPO as an edible oil was investigated through characterizations including refractive index, specific gravity, rheological profile, and NMR spectroscopy. The in vitro radical-scavenging activity of TPO was tested using ABTS assay. The diabetic rats were orally supplemented with two different doses of TPO (high or low) for seven days. The physical parameters, including a refractive index, a specific gravity, and a rheological profile are indicated as favorable attributes of TPO as edible oil. The NMR analysis suggested that TPO contains stearic acid and linolenyl chain compounds. TPO exhibited robust in vitro radical-scavenging activity, with an IC50 of 1.33 µl/ml. In vivo study showed that the total serum lipid content was significantly lower in the TPO treated groups compared to other groups. However, blood glucose level did not reduced in TPO treated groups. The levels of anti-oxidant enzymes CAT and SOD were enhanced by both doses of TPO in diabetic rats indicating the significant anti-oxidant activity of TPO. In addition, Histopathological evaluations indicated no signs of toxicity in hepatic and renal tissues of TPO-treated diabetic rats. Hence, taking into consideration these activities, the tasar pupae oil can be further investigated for its therapeutic and edible properties.

Comparison of Protective Effects of Polyphenol-Enriched Extracts from Thinned Immature Kiwifruits and Mature Kiwifruits against Alcoholic Liver Disease in Mice.

Alcoholic liver disease (ALD) is regarded as one of the main global health problems. Accumulated evidence indicates that fruit-derived polyphenols can lower the risk of ALD, this attributed to their strong antioxidant capacities. Thinned immature kiwifruits (TIK) are the major agro-byproducts in the production of kiwifruits, which have abundantly valuable polyphenols. However, knowledge about the protective effects of polyphenol-enriched extract from TIK against ALD is still lacking, which ultimately restricts their application as value-added functional products. To promote their potential applications, phenolic compounds from TIK and their corresponding mature fruits were compared, and their protective effects against ALD were studied in the present study. The findings revealed that TIK possessed extremely high levels of total phenolics (116.39 ± 1.51 mg GAE/g DW) and total flavonoids (33.88 ± 0.59 mg RE/g DW), which were about 7.4 times and 4.8 times greater than those of their corresponding mature fruits, respectively. Furthermore, the level of major phenolic components in TIK was measured to be 29,558.19 ± 1170.58 μg/g DW, which was about 5.4 times greater than that of mature fruits. In particular, neochlorogenic acid, epicatechin, procyanidin B1, and procyanidin B2 were found as the predominant polyphenols in TIK. In addition, TIK exerted stronger in vitro antioxidant and anti-inflammatory effects than those of mature fruits, which was probably because of their higher levels of polyphenols. Most importantly, compared with mature fruits, TIK exhibited superior hepatoprotective effects on alcohol-induced liver damage in mice. The administration of polyphenol-enriched extract from TIK (YK) could increase the body weight of mice, reduce the serum levels of ALP, AST, and ALT, lower the levels of hepatic TG and TC, and diminish lipid droplet accumulation and hepatic tissue damage. In addition, the treatment of YK could also significantly restore the levels of antioxidant enzymes (e.g., SOD and CAT) in the liver and lower the levels of hepatic proinflammatory cytokines (e.g., IL-6, IL-1β, and TNF-α), indicating that YK could effectively ameliorate ALD in mice by reducing hepatic oxidative stress and hepatic inflammation. Collectively, our findings can provide sufficient evidence for the development of TIK and their extracts as high value-added functional products for the intervention of ALD.

Biochemical Studies on Efficiency of Natural Gum in Chronic Kidney Failure and Liver Cirrhosis in Rats

It is well-established that apoptosis, oxidative stress, and inflammation are associated with several disorders, including chronic renal disease and hepatic disease. Oxidative stress (OS) is a major cause of death from end-stage renal disease which also contributes to atherosclerosis and cardiac issues. The present study aimed to assess the efficacy of Gum Arabic (GA) in mitigating renal damage and hepatotoxicity in rats induced by Chloropyrifos-methyl (CPM). A total of 42 male Wistar rats were divided into seven groups, with four groups (group 2 [IC], group 5 [GA1+IC]a, group 6 [GA2+IC], and group 7 [GA1+IC]b treated with CPM for eight weeks to induce hepatic and renal damage. Two models of GA administration, including the standard oral model in drinking water (15% w/v) and the oral model by gavage at a dose of 1 g/kg body weight were administered. Physiological parameters of kidney and liver functions, including urea, creatinine, AST, and ALT along with anti-oxidant factors (Melaodialdehyde, superoxide dismutase, reduced glutathione, and catalase) were measured in plasma, and homogenates of renal and hepatic tissues on day 57 of the experiment. In addition, histopathological examination was conducted on liver and kidney tissues using hematoxylin and eosin stain to evaluate the efficacy of GA on damaged tissues. Gum Arabic was found to significantly reduce CPM toxic effects in the liver and kidney in groups treated with CPM as liver and kidney parameters were reduced to normal levels. Furthermore, GA reduced histological indicators of inflammation, fibrosis, and apoptosis, as well as renal morphological damage. Additionally, it reduced OS in liver and kidney homogenates. In conclusion, GA effectively reduced the damage that CPM inflicted on liver and kidney tissue by stabilizing physiological parameters to normal levels and repairing cellular structures damaged by OS. Keywords: Antioxidant, Anti-inflammatory, Gum Arabic, Kidney, Liver, Oxidative stress

Comparative Assessment of Beeswax Alcohol and Coenzyme Q10 (CoQ10) to Prevent Liver Aging, Organ Damage, and Oxidative Stress in Hyperlipidemic Zebrafish Exposed to D-Galactose: A 12-Week Dietary Intervention.

The current study was designed to compare in vivo efficacy between beeswax alcohol (BWA) and coenzyme Q10 (CoQ10) to treat fatty liver changes, oxidative stress, and damages in major organs of zebrafish by 12 weeks with high-cholesterol (HC) and galactose (Gal) supplementation. At week 12, the HC control and HC+Gal control groups showed 96% and 92% survivability, respectively, while co-supplementation of the 0.5% BWA and 1.0% BWA groups exhibited 96% and 100% survivability. However, co-supplementation of the 0.5% CoQ10 and 1.0% CoQ10 groups revealed the lowest survivability, around 92% and 89%, respectively. The 0.5% BWA and 1.0% BWA groups showed 21% (p < 0.001) and 41% (p < 0.001), respectively, lower total cholesterol (TC) than the HC+Gal control, while the 1.0% CoQ10 group showed only 15% lower TC than the control. Interestingly, the 0.5% BWA and 1.0% BWA groups showed 22% (p < 0.001) and 38% (p < 0.001), respectively, lower triglyceride (TG) than the HC+Gal control. However, both the 0.5% CoQ10 and 1.0% CoQ10 groups showed similar TG levels as the control, suggesting that CoQ10 supplementation had no effect on lowering serum TG. The 1.0% BWA group showed the highest plasma HDL-C and HDL-C/TC (%) up to 3.2-fold and 5.5-fold, respectively, higher than those of the HC+Gal control, while the 1.0% CoQ10 group showed 2.4-fold and 2.8-fold higher plasma HDL-C and HDL-C/TC (%), respectively, than the control. The plasma aspartate transaminase (AST) and alanine transaminase (ALT) levels were lowest in the 1.0% BWA group, 51% and 72%, respectively, lower than HC+Gal control, suggesting the lowest extent of hepatic damage. In hepatic tissue, neutrophil infiltration and interleukin (IL)-6 production were the lowest in the 1.0% BWA group, around 67% and 85%, respectively, lower than the HC+Gal control. Fatty liver change, cellular apoptosis, and cell senescence in hepatic tissue were remarkably lowered in the 1.0% BWA group, while the CoQ10 group showed much less effect than the BWA group. In kidney, ovary, and testis tissue, the 1.0% BWA group showed the lowest production of reactive oxygen species, the extent of cellular senescence, and cellular apoptosis with the healthiest cell morphology. In conclusion, supplementation of BWA remarkably protected the liver, kidney, ovary, and testis from oxidative damage by cholesterol and galactose consumption, with the least serum AST and ALT levels, inflammatory parameters, and senescence markers.

Haematological and Histological Effects of Nanoplastics Released from Nonfood-grade Nonwoven Polyethene Bags on Mice

Nonfood-grade nonwoven polyethene (NFWP) bags which are frequently used in microwave cooking or carrying hot foods have been reported for releasing large amount of nanoplastics. Hence, the present study was designed to investigate the harmful effects of nanoplastics released from NFWP bags on mice. NFWP bags were cut into small pieces which were then boiled in water for 5 minutes. Then the boiled water was used as nanoplastic-contaminated drinking water for treated mice for 50 days. Surprisingly, the body weights and organ weight were increased remarkably for treated mice than control mice. The total Red Blood Cell (RBC) count decreased remarkably while total WBC count increased significantly in treated mice than in control. The percentage of neutrophils decreased remarkably while percentage of Monocytes increased significantly in treated mice as compared with control. The consumption of nanoplastics caused histological damage to intestine, heart, lung, kidney and liver of treated mice. The layers of intestinal muscles in the villi of treated mice were disrupted and infiltrated with foam cells. Destruction of alveoli and fibrosis was observed in the lungs of the treated mice. The heart muscles of treated mice were also disrupted and irregularly arranged with fibrosis. In the kidney of treated mouse, enhancement of renal spaces, shrinkage of glomeruli, eroded Bowman’s capsule, deleted and congested glomeruli along with blood vessel were found. The liver of the treated mice was affected by apoptosis, fibrosis, vacuole formation in hepatocyte, congested in hepatic tissue and dilation of blood vessel. Therefore, it can be concluded that consumption of nanoplastics released from hot NFWP bags has serious deleterious effect on haematopoiesis and tissue integrity of different organs of Mice.

Development of mRNA Lipid Nanoparticles: Targeting and Therapeutic Aspects.

Lipid nanoparticles (LNPs) have emerged as leading non-viral carriers for messenger RNA (mRNA) delivery in clinical applications. Overcoming challenges in safe and effective mRNA delivery to target tissues and cells, along with controlling release from the delivery vehicle, remains pivotal in mRNA-based therapies. This review elucidates the structure of LNPs, the mechanism for mRNA delivery, and the targeted delivery of LNPs to various cells and tissues, including leukocytes, T-cells, dendritic cells, Kupffer cells, hepatic endothelial cells, and hepatic and extrahepatic tissues. Here, we discuss the applications of mRNA-LNP vaccines for the prevention of infectious diseases and for the treatment of cancer and various genetic diseases. Although challenges remain in terms of delivery efficiency, specific tissue targeting, toxicity, and storage stability, mRNA-LNP technology holds extensive potential for the treatment of diseases.

Effect of senolytic drugs in young female mice chemically induced to estropause

AimsThis study aimed to assess metabolic responses and senescent cell burden in young female mice induced to estropause and treated with senolytic drugs. Main methodsEstropause was induced by 4-vinylcyclohexene diepoxide (VCD) injection in two-month-old mice. The senolytics dasatinib and quercetin (D + Q) or fisetin were given by oral gavage once a month from five to 11 months of age. Key findingsVCD-induced estropause led to increased body mass and reduced albumin concentrations compared to untreated cyclic mice, without affecting insulin sensitivity, lipid profile, liver enzymes, or total proteins. Estropause decreased catalase activity in adipose tissue but had no significant effect on other redox parameters in adipose and hepatic tissues. Fisetin treatment reduced ROS levels in the hepatic tissue of estropause mice. Estropause did not influence senescence-associated beta-galactosidase activity in adipose and hepatic tissues but increased senescent cell markers and fibrosis in ovaries. Senolytic treatment did not decrease ovarian cellular senescence induced by estropause. SignificanceOverall, the findings suggest that estropause leads to minor metabolic changes in young females, and the senolytics D + Q and fisetin had no protective effects despite increased ovarian senescence.