Effective protective agents against organ toxicity of deoxynivalenol and their detoxification mechanisms: A review.

Deoxynivalenol (DON) is one of the most prevalent mycotoxins in feed, which causes organ toxicity in animals. Therefore, reducing DON-induced organ toxicity can now be accomplished effectively using protective agents. This review provides an overview of multiple studies on a wide range of protective agents and their molecular mechanisms against DON organ toxicity. Protective agents include plant extracts, yeast products, bacteria, peptides, enzymes, H2, oligosaccharides, amino acids, adsorbents, vitamins and selenium. Among these, biological detoxification of DON using microorganisms to reduce the toxicity of DON without affecting the growth performance of pigs may be the most promising detoxification strategy. This paper also evaluates future developments related to DON detoxification and discusses the detoxification role and application potential of protective agents. This paper provides new perspectives for future research and development of safe and effective feed additives.

Mechanism of testicular injury induced by Di-ethylhexyl phthalate and its protective agents.

Di-ethylhexyl phthalate (DEHP) is used as an important plasticizer in a wide range of products such as paints, food packaging, medical devices and children's toys. In recent years, there has been increasing interest in the toxic effects of DEHP on the male reproductive organs, the testicles. Here, we reviewed the basic pathways of testicular damage caused by DEHP. The mechanism involves oxidative stress, ferroptosis, interfering with hypothalamic-pituitary-gonadal axis (HPGA) and testosterone level. We summarized the protective agents that have been shown to be effective in repairing this type of testicular damage in recent years. This provides a new perspective and direction for future research into the health effects and molecular mechanisms of DEHP.

Peptides from Antarctic krill (Euphausia superba) ameliorate acute liver injury in mice induced by carbon tetrachloride via activating the Nrf2/HO-1 pathway.

This study aimed to evaluate the hepatoprotective effects of peptides from Antarctic krill (AKP) on carbon tetrachloride (CCl4)-induced acute liver injury (ALI) in mice and the underlying molecular mechanisms. ICR mice were pretreated with AKP (500 mg kg-1, i.g.) and silybin (30 mg kg-1, i.g.) for 15 days before CCl4 (0.25 mL per kg BW, i.p.) injection. To assess hepatocellular damage and molecular indices, the serum and liver tissue were evaluated at harvest. The results showed that AKP pretreatment remarkably attenuated CCl4-induced liver injury, which was identified by the decrease in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviation of hepatocyte necrosis, and inhibition of the levels of the pro-inflammatory factors TNF-α and IL-1ß compared to those for silymarin. AKP pretreatment also enhanced the redox balance by reducing the concentrations of MDA and 8-iso-PG and increasing the activities of SOD, GSH and GSH-PX in the liver of mice. In addition, AKP upregulated oxidative stress-related mRNA expressions of Nrf2, Keap1, HO-1, and NQO1 and further activated the protein expression on the Nrf2/HO-1 singling pathway. In summary, AKP might be a promising hepatoprotective nutraceutical against ALI and its underlying mechanisms are associated with activation of the Nrf2/HO-1 pathway.

Evaluation of the hepatoprotective effect of naringenin loaded nanoparticles against acetaminophen overdose toxicity.

Acute liver injury is a common clinical disease, which easily leads to liver failure and endangers life, seriously threatening human health. Naringenin is a natural flavonoid that holds therapeutic potential against various liver injuries; however it has poor water solubility and bioavailability. In this study, we aimed to develop naringenin-loaded bovine serum albumin nanoparticles (NGNPs) and to evaluate their hepatoprotective effect and underlying mechanisms against acetaminophen overdose toxicity. In vitro data indicated that NGNPs significantly increased the drug solubility and also more effectively protected the hepatocyte cells from oxidative damage during hydrogen peroxide exposure or lipopolysaccharide (LPS) stimulation. In vivo results confirmed that NGNPs showed an enhanced accumulation in the liver tissue. In the murine model of acetaminophen-induced hepatotoxicity, NGNPs could effectively alleviate the progression of acute liver injury by reducing drug overdose-induced levels of oxidative stress, inflammation and apoptosis in hepatocytes. In conclusion, NGNPs has strong hepatoprotective effects against acetaminophen induced acute liver injury.

KLF11 Is a Novel Endogenous Protectant against Renal Ischemia-Reperfusion Injury.

Discovering new nephroprotectants may provide therapeutic strategies in AKI.This study provides the first evidence that KLF11, a member of the Krüppel-like factor (KLF) family of proteins, protects against AKI.In the absence of KLF11, exaggerated induction of endothelin-1 and IL-6 occurs after ischemic renal injury and may contribute to worse AKI.

The role of Bax/Bcl-2 and Nrf2-Keap-1 signaling pathways in mediating the protective effect of boric acid on acrylamide-induced acute liver injury in rats.

INTRODUCTION: This study aims to investigate whether boric acid (BA) can protect rats from acrylamide (AA)-induced acute liver injury. MATERIALS AND METHODS: AA was used to induce acute liver injury. Thirty rats were divided into five group including Group 1 (saline), Group 2 (AA), Group 3 (20 mg/kg BA), Group 4 (10 mg/kg BA+AA) and Group 5 (20 mg/kg BA+AA). Their blood and liver were harvested to be kept for analysis. Liver function enzyme activities were performed by spectrophotometric method. Catalase (CAT), superoxide dismutase (SOD) activity, and malondialdehyde levels were determined by colorimetric method. The in-silico studies were performed using the "blind docking" method. RESULTS: Administration AA to rats, biochemical parameters, liver histology, and expression levels of apoptotic markers were negatively affected. However, after the administration of BA, the altered biochemical parameters, liver histology, and expression levels of apoptotic markers were reversed. Moreover, the mechanisms of AA-induced deterioration in the levels of SOD, CAT, and Nrf2-Keap-1 and the mechanisms of the protective effect of BA against these deteriorations were explained by in silico studies. CONCLUSION: Thus, the present study could explain the interactions between AA and thiol-containing amino acid residues of Keap-1, the effect of BA on these interactions, and the biochemical toxicity caused by the AA. In this sense, this work is the first of its kind in the literature. Based on the biochemical, histopathological, and in silico results, it can be suggested that BA has the potential to be used as a protective agent against AA-induced liver injury.

Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential.

Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate (Punica granatum L.) and in wood and bark of some tree species. Structurally, EA is a dilactone of hexahydroxydiphenic acid (HHDP), a dimeric gallic acid derivative, produced mainly by hydrolysis of ellagitannins, a widely distributed group of secondary metabolites. EA is attracting attention due to its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties. EA displayed pharmacological effects in various in vitro and in vivo model systems. Furthermore, EA has also been well documented for its antiallergic, antiatherosclerotic, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties. This review reports on the health-promoting effects of EA, along with possible mechanisms of its action in maintaining the health status, by summarizing the literature related to the therapeutic potential of this polyphenolic in the treatment of several human diseases.

NRF2-mediated SIRT3 induction protects hepatocytes from ER stress-induced liver injury.

Chronic endoplasmic reticulum (ER) stress in hepatocytes plays a role in the pathogenesis of nonalcoholic fatty liver disease. Therefore, given the association between oxidative stress, mitochondrial dysfunction, and ER stress, our study investigated the role of NRF2-mediated SIRT3 activation in ER stress. SIRT3, a sirtuin, was predicted as the target of NRF2 based on bioinformatic analyses and animal experiments. Nrf2 abrogation diminished mitochondrial DNA content in hepatocytes with Ppargc1α and Cpt1a inhibition, whereas its overexpression enhanced oxygen consumption. Further, chromatin immunoprecipitation and luciferase reporter assays indicated that NRF2 induced SIRT3 through the antioxidant responsive element (ARE) sites comprising the -641 to -631 bp and -419 to -409 bp regions. In tunicamycin-induced ER stress conditions and liver injury animal models following ER stress, NRF2 levels were highly correlated with SIRT3. Nrf2 deficiency enhanced the tunicamycin-mediated induction of CHOP, which was attenuated by Sirt3 overexpression. Further, Sirt3 delivery to hepatocytes in Nrf2 knockout mice prevented tunicamycin from increasing mortality by decreasing ER stress. SIRT3 was upregulated in livers of patients with nonalcoholic liver diseases, whereas lower SIRT3 expression coincided with more severe disease conditions. Taken together, our findings indicated that NRF2-mediated SIRT3 induction protects hepatocytes from ER stress-induced injury, which may contribute to the inhibition of liver disease progression.

Glutaredoxin 1 controls monocyte reprogramming during nutrient stress and protects mice against obesity and atherosclerosis in a sex-specific manner.

High-calorie diet-induced nutrient stress promotes thiol oxidative stress and the reprogramming of blood monocytes, giving rise to dysregulated, obesogenic, proatherogenic monocyte-derived macrophages. We report that in chow-fed, reproductively senescent female mice but not in age-matched male mice, deficiency in the thiol transferase glutaredoxin 1 (Grx1) promotes dysregulated macrophage phenotypes as well as rapid weight gain and atherogenesis. Grx1 deficiency derepresses distinct expression patterns of reactive oxygen species and reactive nitrogen species generators in male versus female macrophages, poising female but not male macrophages for increased peroxynitrate production. Hematopoietic Grx1 deficiency recapitulates this sexual dimorphism in high-calorie diet-fed LDLR-/- mice, whereas macrophage-restricted overexpression of Grx1 eliminates the sex differences unmasked by high-calorie diet-feeding and protects both males and females against atherogenesis. We conclude that loss of monocytic Grx1 activity disrupts the immunometabolic balance in mice and derepresses sexually dimorphic oxidative stress responses in macrophages. This mechanism may contribute to the sex differences reported in cardiovascular disease and obesity in humans.

Protective effect of H2S on LPS­induced AKI by promoting autophagy.

The present study explored the protective effect of exogenous hydrogen sulfide (H2S) on lipopolysaccharide (LPS)­induced acute kidney injury (AKI) and the underlying mechanisms. To establish an AKI injury mouse model, LPS (10 mg/kg) was intraperitoneally injected into mice pretreated with 0.8 mg/kg sodium hydrosulfide hydrate (NaHS), an H2S donor. The mouse survival rate and the degree of kidney injury were examined. To construct a cell damage model, HK­2 cells were pretreated with different concentrations (0.1, 0.3 and 0.5 mM) of NaHS, and then the cells were stimulated with LPS (1 µg/ml). The cell viability, autophagy, apoptosis levels and the release of inflammatory factors were examined in mouse kidney tissue and HK­2 renal tubular epithelial cells. It was found that pretreatment with NaHS significantly improved the survival rate of septic AKI mice, and reduced the renal damage, release of inflammatory factors and apoptosis. In HK­2 cells, NaHS protected cells from LPS caused damage via promoting autophagy and inhibiting apoptosis and the release of inflammatory factors. In order to clarify the relationship between autophagy and apoptosis and inflammatory factors, this study used 3­methyladenine (3­MA) to inhibit autophagy. The results revealed that 3­MA eliminated the protective effect of NaHS in HK­2 cells and AKI mice. Overall, NaHS can protect from LPS­induced AKI by promoting autophagy and inhibiting apoptosis and the release of inflammatory factors.

PGC-1α inhibits the NLRP3 inflammasome via preserving mitochondrial viability to protect kidney fibrosis.

The NLRP3 inflammasome is activated by mitochondrial damage and contributes to kidney fibrosis. However, it is unknown whether PGC-1α, a key mitochondrial biogenesis regulator, modulates NLRP3 inflammasome in kidney injury. Primary renal tubular epithelial cells (RTECs) were isolated from C57BL/6 mice. The NLRP3 inflammasome, mitochondrial dynamics and morphology, oxidative stress, and cell injury markers were examined in RTECs treated by TGF-ß1 with or without Ppargc1a plasmid, PGC-1α activator (metformin), and siPGC-1α. In vivo, adenine-fed and unilateral ureteral obstruction (UUO) mice were treated with metformin. In vitro, TGF-ß1 treatment to RTECs suppressed the expressions of PGC-1α and mitochondrial dynamic-related genes. The NLRP3 inflammasome was also activated and the expression of fibrotic and cell injury markers was increased. PGC-1α induction with the plasmid and metformin improved mitochondrial dynamics and morphology and attenuated the NLRP3 inflammasome and cell injury. The opposite changes were observed by siPGC-1α. The oxidative stress levels, which are inducers of the NLRP3 inflammasome, were increased and the expression of TNFAIP3, a negative regulator of NLRP3 inflammasome regulated by PGC-1α, was decreased by TGF-ß1 and siPGC-1α. However, PGC-1α restoration reversed these alterations. In vivo, adenine-fed and UUO mice models showed suppression of PGC-1α and TNFAIP3 and dysregulated mitochondrial dynamics. Moreover, the activation of oxidative stress and NLRP3 inflammasome, and kidney fibrosis were increased in these mice. However, these changes were significantly reversed by metformin. This study demonstrated that kidney injury was ameliorated by PGC-1α-induced inactivation of the NLRP3 inflammasome via modulation of mitochondrial viability and dynamics.

A gliclazide complex based on palladium towards Alzheimer's disease: promising protective activity against Aß-induced toxicity in C. elegans.

A new palladium coordination compound based on gliclazide with the chemical formula [Pd(glz)2] (where glz = gliclazide) has been synthesized and characterised. The structural characterization reveals that this material consists of mononuclear units formed by a Pd2+ ion coordinated to two molecules of the glz ligand, in which palladium ions exhibit a distorted plane-square coordination sphere. This novel material behaves like a good and selective inhibitor of butyrylcholinesterase, one of the most relevant therapeutic targets against Alzheimer's disease. Analysis of the enzyme kinetics showed a mixed mode of inhibition, the title compound being capable of interacting with both the free enzyme and the enzyme-substrate complex. Finally, the palladium compound shows promising protective activity against Aß-induced toxicity in the Caenorhabditis elegans model, which has never been reported.

Neuron-derived neurotrophic factor protects against dexamethasone-induced skeletal muscle atrophy.

Skeletal muscle atrophy caused by various conditions including aging, nerve damage, and steroid administration, is a serious health problem worldwide. We recently reported that neuron-derived neurotrophic factor (NDNF) functions as a muscle-derived secreted factor, also known as myokine, which exerts protective actions on endothelial cell and cardiomyocyte function. Here, we investigated whether NDNF regulates skeletal muscle atrophy induced by steroid administration and sciatic denervation. NDNF-knockout (KO) mice and age-matched wild-type (WT) mice were subjected to continuous dexamethasone (DEX) treatment or sciatic denervation. NDNF-KO mice exhibited decreased gastrocnemius muscle weight and reduced cross sectional area of myocyte fiber after DEX treatment or sciatic denervation compared with WT mice. Administration of an adenoviral vector expressing NDNF (Ad-NDNF) or recombinant NDNF protein to gastrocnemius muscle of WT mice increased gastrocnemius muscle weight after DEX treatment. NDNF-KO mice showed increased expression of ubiquitin E3-ligases, including atrogin-1 and MuRF-1, in gastrocnemius muscle after DEX treatment, whereas Ad-NDNF reduced expression of atrogin-1 and MuRF-1 in gastrocnemius muscle of WT mice after DEX treatment. Pretreatment of cultured C2C12 myocytes with NDNF protein reversed reduced myotube diameter and increased expression of atrogin-1 and MuRF-1 after DEX stimulation. Treatment of C2C12 myocytes increased Akt phosphorylation. Pretreatment of C2C12 myotubes with the PI3-kinase/Akt inhibitor reversed NDNF-induced increase in myotube fiber diameter after DEX treatment. In conclusion, our findings indicated that NDNF prevents skeletal muscle atrophy in vivo and in vitro through reduction of ubiquitin E3-ligases expression, suggesting that NDNF could be a novel therapeutic target of muscle atrophy.

Membrane-delimited signaling and cytosolic action of MG53 preserve hepatocyte integrity during drug-induced liver injury.

BACKGROUND & AIMS: Drug-induced liver injury (DILI) remains challenging to treat and is still a leading cause of acute liver failure. MG53 is a muscle-derived tissue-repair protein that circulates in the bloodstream and whose physiological role in protection against DILI has not been examined. METHODS: Recombinant MG53 protein (rhMG53) was administered exogenously, using mice with deletion of Mg53 or Ripk3. Live-cell imaging, histological, biochemical, and molecular studies were used to investigate the mechanisms that underlie the extracellular and intracellular action of rhMG53 in hepatoprotection. RESULTS: Systemic administration of rhMG53 protein, in mice, can prophylactically and therapeutically treat DILI induced through exposure to acetaminophen, tetracycline, concanavalin A, carbon tetrachloride, or thioacetamide. Circulating MG53 protects hepatocytes from injury through direct interaction with MLKL at the plasma membrane. Extracellular MG53 can enter hepatocytes and act as an E3-ligase to mitigate RIPK3-mediated MLKL phosphorylation and membrane translocation. CONCLUSIONS: Our data show that the membrane-delimited signaling and cytosolic dual action of MG53 effectively preserves hepatocyte integrity during DILI. rhMG53 may be a potential treatment option for patients with DILI. LAY SUMMARY: Interventions to treat drug-induced liver injury and halt its progression into liver failure are of great value to society. The present study reveals that muscle-liver cross talk, with MG53 as a messenger, serves an important role in liver cell protection. Thus, MG53 is a potential treatment option for patients with drug-induced liver injury.

Discovery of novel ketamine-inspired derivatives as a protective agent against renal ischemic/reperfusion injury in Wistar rats.

Renal ischemia-reperfusion (I/R) injury is a limiting factor for the success of renal grafts and is deemed greatly responsible for the mortality. A novel series of ketamine-inspired compounds was synthesized and subjected to NF-ĸB transcriptional inhibitory activity in LPS-stimulated RAW264.7 cells, where entire set of compounds showed mild-to-moderate significant NF-ĸB transcriptional inhibitory activity (IC50 6.53-67.52 µM). Compound 6d showed highest inhibitory activity among the tested series (IC50 2.62 µM) and found more potent as compared to ketamine as standard. The effect of compound 6d was further quantified in I/R injury in Wistar rats, where it dose-dependently improves kidney function of rats with significant amelioration of kidney injury as suggested by histopathologic examination of renal tissues. It further showed reduction in the generation of pro-inflammatory cytokines and improves the antioxidant status of experimental rats. Compound 6d inhibited apoptosis and increases the expression of Bcl2 and decreases Bax, and cleaved caspase-3 level. It further reduces TLR-4 and NF-κB expression in renal cells of rats, with increases in IκB-α level in Western blot analysis as compared to I/R group. In summary, our current study showed the development of a novel class of ketamine-inspired derivatives against renal ischemia/reperfusion injury.

Expression and role of microRNA-212/nuclear factor I-A in depressive mice.

Depression is characterized by persistent depressed mood and cognitive dysfunction, severely impacting human health. In the present study, we aimed to explore the role and mechanism of microRNA (miR)-212 in depression in vivo. Chronic unpredictable mild stress (CUMS) mice were established, and depression-like behaviors were confirmed using the forced swimming test (FST), sucrose preference test (SPT), and the tail suspension test (TST). Next, the expression of miR-212 and its potential target, i.e., nuclear factor I-A (NFIA), was verified using quantitative reverse transcription (qRT)-PCR analysis and Western blotting in CUMS mice. The effects of miR-212 and NFIA on depression-like behaviors, inflammatory response, and neuronal apoptosis were examined using FST, TST, SPT, enzyme-linked immunosorbent assay (ELISA) assay, and flow cytometry analysis. Finally, the relationship between miR-212 and NFIA was examined using a dual-luciferase reporter assay. Based on our findings, miR-212 was significantly upregulated, while NFIA was downregulated in CUMS mice. miR-212 overexpression could suppress the CUMS-induced weight loss, immobility time in FST and TST, and increased hippocampal neuronal apoptosis and pro-inflammatory cytokines levels. In addition, NFIA upregulation could partially reverse the effects of miR-212 mimic in CUMS mice. Accordingly, miR-212 could ameliorate CUMS-induced depression-like behavior in mice by targeting NFIA, indicating its protective role in depression.

Mechanism of M2 macrophage-derived extracellular vesicles carrying lncRNA MEG3 in inflammatory responses in ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. M2 macrophages possess certain anti-inflammation activity. Accordingly, the current study set out to investigate the potential mechanism of M2 macrophage-derived extracellular vesicles (M2-EVs) in UC inflammation. Firstly, mouse peritoneal macrophages were induced to M2 phenotype, and M2-EVs were isolated. , the murine model of UC was established, and the length and weight of the colon, disease activity index (DAI), apoptosis, and inflammatory response of UC mice were measured. Young adult mouse colon (YAMC) cells were induced with the help of lipopolysaccharide. LncRNA maternally expressed 3 (LncRNA MEG3), miR-20b-5p, and cAMP responsive element binding protein 1 (CREB1) expression patterns were detected in UC models. In addition, we analyzed the binding relationship among MEG3, miR-20b-5p, and CREB1. UC mice presented with shortened colon length, lightened weight, increased DAI score, enhanced apoptosis, and significant inflammatory cell infiltration, while M2-EVs reversed these trends. In vitro, M2-EVs increased UC cell viability and reduced inflammation. Mechanistic experimentation revealed that M2-EVs transferred MEG3 into YAMC cells to up-regulate MEG3 expression and promote CREB1 transcription by competitively binding to miR-20b-5p. Moreover, up-regulation of MEG3 in M2-EVs enhanced the protective effect of M2-EVs on UC cells, while over-expression of miR-20b-5p attenuated the aforementioned protective effect of M2-EVs on UC mice and cells. Collectively, our findings revealed that M2-EVs carrying MEG3 enhanced UC cell viability and reduced inflammatory responses via the miR-20b-5p/CREB1 axis, thus alleviating UC inflammation.

Secondary Metabolite Profiling, Anti-Inflammatory and Hepatoprotective Activity of Neptunia triquetra (Vahl) Benth.

The present study aimed to analyze the phytoconstituents of Neptunia triquetra (Vahl) Benth. Anti-inflammatory and hepatoprotective activities of ethanol (EE), chloroform (CE) and dichloromethane (DCME) of stem extracts were evaluated using in vivo experimental models. The extracts were analyzed for phytoconstituents using GC-HRMS. Anti-inflammatory activity of CE, EE and DCME was accessed using carrageenan-induced paw oedema, cotton pellet-induced granuloma and the carrageenan-induced air-pouch model in Wistar albino rats. The hepatotoxicity-induced animal models were investigated for the biochemical markers in serum (AST, ALT, ALP, GGT, total lipids and total protein) and liver (total protein, total lipids, GSH and wet liver weight). In the in vivo study, animals were divided into different groups (six in each group) for accessing the anti-inflammatory and hepatoprotective activity, respectively. GC-HRMS analysis revealed the presence of 102 compounds, among which 24 were active secondary metabolites. In vivo anti-inflammatory activity of stem extracts was found in the order: indomethacin > chloroform extract (CE) > dichloromethane extract (DCME) > ethanolic extract (EE), and hepatoprotective activity of stem extracts in the order: CE > silymarin > EE > DCME. The results indicate that N. triquetra stem has a higher hepatoprotective effect than silymarin, however the anti-inflammatory response was in accordance with or lower than indomethacin.

Nano-Structured Lipid Carrier-Based Oral Glutathione Formulation Mediates Renoprotection against Cyclophosphamide-Induced Nephrotoxicity, and Improves Oral Bioavailability of Glutathione Confirmed through RP-HPLC Micellar Liquid Chromatography.

The study aimed to develop a new glutathione (GSH) oral formulation to enhance the delivery of GSH and counter the nephrotoxicity of the anticancer drug, cyclophosphamide (CP). A nanostructured lipid carrier glutathione formulation (GSH-NLCs) composed of glutathione (500 mg), stearic and oleic acid (300 mg, each), and Tween® 80 (2%, w/v) was prepared through the emulsification-solvent-evaporation technique, which exhibited a 452.4 ± 33.19 nm spheroidal-sized particulate material with narrow particle size distributions, -38.5 ± 1.4 mV zeta potential, and an entrapment efficiency of 79.8 ± 1.9%. The GSH formulation was orally delivered, and biologically tested to ameliorate the CP-induced renal toxicity in a rat model. Detailed renal morphology, before and after the GSH-NLCs administration, including the histopathological examinations, confirmed the ameliorating effects of the prepared glutathione formulation together with its safe oral delivery. CP-induced oxidative stress, superoxide dismutase depletion, elevation of malondialdehyde levels, depletion of Bcl-2 concentration levels, and upregulated NF-KB levels were observed and were controlled within the recommended and near normal/control levels. Additionally, the inflammatory mediator marker, IL-1ß, serum levels were marginally normalized by delivery of the GHS-NLCs formulation. Oral administration of the pure glutathione did not exhibit any ameliorating effects on the renal tissues, which suggested that the pure glutathione is reactive and is chemically transformed during the oral delivery, which affected its pharmacological action at the renal site. The protective effects of the GSH-NLCs formulation through its antioxidant and anti-inflammatory effects suggested its prominent role in containing CP-induced renal toxicity and renal tissue damage, together with the possibility of administrating higher doses of the anticancer drug, cyclophosphamide, to achieve higher and effective anticancer action in combination with the GSH-NLCs formulation.

Hepatoprotective Effects of Bioflavonoid Luteolin Using Self-Nanoemulsifying Drug Delivery System.

Luteolin (LUT) is a natural pharmaceutical compound that is weakly water soluble and has low bioavailability when taken orally. As a result, the goal of this research was to create self-nanoemulsifying drug delivery systems (SNEDDS) for LUT in an attempt to improve its in vitro dissolution and hepatoprotective effects, resulting in increased oral bioavailability. Using the aqueous phase titration approach and the creation of pseudo-ternary phase diagrams with Capryol-PGMC (oil phase), Tween-80 (surfactant), and Transcutol-HP (co-emulsifier), various SNEDDS of LUT were generated. SNEDDS were assessed for droplet size, polydispersity index (PDI), zeta potential (ZP), refractive index (RI), and percent of transmittance (percent T) after undergoing several thermodynamic stability and self-nanoemulsification experiments. When compared to LUT suspension, the developed SNEDDS revealed considerable LUT release from all SNEDDS. Droplet size was 40 nm, PDI was <0.3, ZP was -30.58 mV, RI was 1.40, percent T was >98 percent, and drug release profile was >96 percent in optimized SNEDDS of LUT. For in vivo hepatoprotective testing in rats, optimized SNEDDS was chosen. When compared to LUT suspension, hepatoprotective tests showed that optimized LUT SNEDDS had a substantial hepatoprotective impact. The findings of this investigation suggested that SNEDDS could improve bioflavonoid LUT dissolution rate and therapeutic efficacy.