Resveratrol-Based Liposomes Improve Cardiac Remodeling Induced by Isoproterenol Partially by Modulating MEF2, Cytochrome C and S100A1 Expression.

Isoproterenol (ISO), a chemically synthesized catecholamine, belongs to ß-adrenoceptor agonist used to treat bradycardia. The ß-adrenergic agonist is an essential regulator of myocardial metabolism and contractility; however, excessive exposure to ISO can initiate oxidative stress and inflammation. This study aims to investigate the molecular mechanisms underlying ISO-induced cardiac remodeling, the protective efficacy of resveratrol (RSVR), and its liposomal formulation (L-RSVR) against such cardiac change. Wistar albino rats were evenly divided into 4 groups. Control group, ISO group received ISO (50 mg/kg, s.c.) twice a week for 2 weeks, and RSVR- and L-RSVR-treated groups in which rats received either RSVR or L-RSVR (20 mg/kg/day, p.o.) along with ISO for 2 weeks. ISO caused a significant elevation of the expression levels of BAX and MEF2 mRNA, S100A1 and cytochrome C proteins, as well as DNA fragmentation in cardiac tissue compared to the control group. Treatment with either RSVR or L-RSVR for 14 days significantly ameliorated the damage induced by ISO, as evidenced by the improvement of all measured parameters. The present study shows that L-RSVR provides better cardio-protection against ISO-induced cardiac injury in rats, most likely through modulation of cardiac S100A1 protein expression and inhibition of inflammation and apoptosis.

Implication of MAPK, Lipocalin-2, and Fas in the protective action of liposomal resveratrol against isoproterenol-induced kidney injury.

Background and Objective: Isoproterenol (ISO) is a non-selective ß-adrenergic receptor agonist. It can be used to treat bradycardia and cardiogenic shock. Despite its usefulness, the overstimulation of ß-receptors by ISO can cause "cardiorenal syndrome," a term used to describe heart and kidney damage. Resveratrol (RES), a natural polyphenol, has marked anti-inflammatory and antioxidant activities. The present work was designed to study the protective efficacy of liposomal resveratrol (L-RES) against ISO-induced kidney injury. Materials and Methods: The kidney injury was induced in rats by administering ISO (50 mg/kg, s.c.) twice a week for 2 weeks. RES and L-RES were administered at a dose (20 mg/kg/ day, p.o.) along with ISO for 2 weeks. Inflammatory and apoptotic biomarkers were analyzed, which were validated using histochemical analysis. Results: ISO caused renal dysfunction, which manifested as elevated urea, creatinine and uric acid, besides cystatin c and MAPK protein overexpression. In addition, ISO induced gene expression of Fas and lipocalin-2 and provoked genomic DNA fragmentation in renal tissues as compared with the control group. Histological examination confirmed morphological alterations of the kidney tissues obtained from the ISO group. Concurrent treatment of either RES or L-RES with ISO significantly ameliorated kidney damage as demonstrated by the improvement of all measured parameters with the best results for L-RES. The histopathological findings were correlated with the above biochemical parameters. Conclusion: L-RES could be a promising approach for the prevention of kidney injury induced by ISO, most likely via the downregulation of MAPK, cystatin c, Fas, and lipocalin-2.

Simvastatin mitigates diabetic nephropathy by upregulating farnesoid X receptor and Nrf2/HO-1 signaling and attenuating oxidative stress and inflammation in rats.

Diabetic nephropathy is one of the complications of diabetes that affects the kidney and can result in renal failure. The cholesterol-lowering drug simvastatin (SIM) has shown promising effects against diabetic nephropathy (DN). This study evaluated the protective role of SIM on DN, pointing to the involvement of farnesoid X receptor (FXR) and Nrf2/HO-1 signaling in attenuating inflammatory response, oxidative injury, and tissue damage in streptozotocin-induced diabetic rats. SIM was supplemented orally for 8 weeks, and samples were collected for analysis. SIM effectively ameliorated hyperglycemia, kidney hypertrophy, body weight loss, and tissue injury and fibrosis in diabetic animals. SIM mitigated oxidative stress (OS), inflammatory response, and cell death, as evidenced by the suppressed malondialdehyde, nitric oxide, myeloperoxidase, NF-kB, TNF-α, IL-1ß, CD68, Bax, and caspase-3 in the diabetic kidney. These effects were linked to suppressed Keap1, upregulated FXR, Nrf2, and HO-1, and enhanced antioxidant defenses and Bcl-2. The in silico findings revealed the binding affinity of SIM with NF-kB, caspase-3, Keap1, HO-1, and FXR. In conclusion, SIM protects against DN by attenuating hyperglycemia, kidney injury, fibrosis, inflammation, and OS, and upregulating antioxidants, FXR, and Nrf2/HO-1 signaling.

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

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

Formulation and In Vivo Evaluation of Biofilm Loaded with Silver Sulfadiazine for Burn Healing.

Infected burned skin is a life-threatening condition, which may lead to sepsis. The aims of this work are to formulate a biofilm composed of silver sulfadiazine (SSD), chitosan (CS), and sodium alginate (SA), and to evaluate its wound-healing effectiveness. A full factorial design was used to formulate different matrix formulations. The prepared biofilm was tested for physicochemical, and in vitro release. The optimized formulation is composed of 0.833% of CS and 0.75% of SA. The release of SSD almost reached 100% after 6 h. The mechanical properties of the optimized formula were reasonable. The antibacterial activity for the optimized biofilm was significantly higher than that of blank biofilm, which is composed of CS and SA, p = 1.53922 × 10-12. Moreover, the in vivo study showed a 75% reduction in wound width when using the formulated SSD biofilm compared to standard marketed cream (57%) and the untreated group (0%).

The implication of LPS/TLR4 and FXR receptors in hepatoprotective efficacy of indole-3-acetic acid and chenodeoxycholic acid.

AIM: Valproic acid (VPA) belongs to the first-generation antiepileptic drugs, yet its prolonged use can cause life-threatening liver damage. The importance of our study is to investigate the protective effect of indole-3-acetic acid (IAA), chenodeoxycholic acid (CDCA) and their combination on VPA-induced liver injury focusing on lipopolysaccharides (LPS)/toll-like receptor 4 (TLR4) pathway and farnesoid X receptor (FXR). METHODS: Thirty rats were randomly assigned into five groups, normal control group, VPA group received 500 mg/kg of VPA intraperitoneally. The remaining groups were orally treated with either 40 mg/kg of IAA, 90 mg/kg of CDCA, or a combination of both, along with VPA. All treatments were administered one hour after the administration of VPA for three weeks. KEY FINDINGS: VPA group showed significant elevations in the liver weight/body weight ratio, serum aminotransferases, triglyceride, and total cholesterol levels. Hepatic glutathione (GSH) level and superoxide dismutase (SOD) activity were significantly decreased, while malondialdehyde (MDA) level, tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1ß), lipopolysaccharide (LPS) and caspase 3 were significantly increased. Likewise, immunohistochemical analysis revealed that TLR4 expression was elevated, whereas FXR expression was downregulated in hepatocytes. IAA substantially ameliorated all previously altered parameters, whereas CDCA treatment showed a partial improvement compared to IAA. Surprisingly, combination therapy of IAA with CDCA showed an additive effect only in the hepatic expression of TLR4 and FXR proteins. SIGNIFICANCE: IAA could be a promising protective agent against VPA-induced liver injury.

Involvement of Nrf2, JAK and COX pathways in acetaminophen-induced nephropathy: Role of some antioxidants.

Objectives: Acetaminophen (APAP)-induced nephrotoxicity is detrimental consequence for which there has not been a standardized therapeutic regimen. Although, N-acetylcysteine (NAC) is a well-known antidote used in APAP-induced hepatotoxicity, its benefit in nephrotoxicity caused by APAP is almost lacking. This study aimed to compare the possible protective effect of thymoquinone (TQ), curcumin (CR), and α-lipoic acid (α-LA), either in solo or in combination regimens with that of NAC against APAP-induced renal injury. Design and method: Rats were divided into nine groups; control group, APAP intoxicated group (1000 mg/kg; orally), and the remaining seven groups received, in addition to APAP, oral doses of NAC, TQ, CR, α-LA, CR plus TQ, TQ plus α-LA, or CR plus α-LA. The first dose of the aforementioned antioxidants was given 24 h before APAP, and then the second dose was given 2 h after APAP, whereas the last dose was given 10 h after administration of APAP. Results: Treatment with APAP elevated kidney markers like serum uric acid, urea, and creatinine. In addition, it increased the serum level of tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß) and thiobarbituric acid reactive species (TBARS). Also, the protein expression of renal janus kinase (JAK) and cyclooxygenase (COX)-2 were all upregulated by APAP. In contrast, the expression of Nrf2 and the renal levels of superoxide dismutase and glutathione were downregulated. Treatment with the indicated natural antioxidants resulted in amelioration of the aberrated parameters through exhibiting anti-inflammatory, antioxidant and free radical-scavenging effects with a variable degree. Conclusion: The combined administration of CR and TQ exerted the most potent protection against APAP-induced nephrotoxicity through its anti-inflammatory and free radical-scavenging effects (antioxidant) which were comparable to that of NAC-treatment.

Roles of Nrf2/HO-1 and ICAM-1 in the Protective Effect of Nano-Curcumin against Copper-Induced Lung Injury.

Copper (Cu) is an essential trace element for maintaining normal homeostasis in living organisms. Yet, an elevated level of Cu beyond homeostatic capacity may lead to oxidative damage of cellular components in several organs, including the lungs. This work investigated the effects of curcumin (Curc) and nano-curcumin (nCurc) against Cu-induced lung injury, accenting the roles of oxidative stress, inflammation, and the nuclear factor erythroid 2-related factor/heme oxygenase-1 Nrf2/HO-1 pathway. Rats were challenged with 100 mg/kg of copper sulfate (CuSO4) while being treated with Curc or nCurc for 7 days. Cu-triggered lung oxidative stress detected as dysregulation of oxidative/antioxidant markers, a downregulation of Nrf-2/HO-1 signaling, and an increase in the inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and intracellular adhesion molecule-1 (ICAM-1). Additionally, it decreased the expression of lung-specific proteins, surfactant protein-C (SP-C), and mucin-1 (MUC-1), induced apoptosis, and caused changes in lung histology. Curc and nCurc alleviated CuSO4-induced lung injury by suppressing oxidative damage and inflammation and activating Nrf-2/HO-1. They also prevented apoptosis and restored the normal expression of SP-C and MUC-1. We concluded that nCurc exhibited superior efficacy compared with Curc in mitigating CuSO4-induced lung injury. This was associated with reduced oxidative stress, inflammation, and apoptotic responses and increased Nrf2/HO-1 signaling and expression of SP-C and MUC-1.

The Association between Cardiovascular Risk Factors and Carotid Intima-Media Thickness in 42,726 Adults in UK Biobank: A Cross-Sectional Study.

BACKGROUND: Traditional modifiable cardiovascular risk factors, such as high blood pressure, have long been positively correlated with high carotid intima-media thickness (cIMT). However, traditional cardiovascular risk factors made a minor contribution to cIMT variance, meaning that other markers may be regarded as independent markers for increasing cIMT. AIMS: To investigate the simple demographic patterns of carotid intima-media thickness (cIMT) in the UK Biobank and to identify which upstream cardiovascular disease (CVD) risk factors are independently associated with cIMT. METHODS AND RESULTS: A cross-sectional-based study of healthy middle-aged people recruited in the UK between 2006 and 2010 (n = 42,726). RESULTS: This study showed that the cardiovascular risk profile generally worsened across the cIMT quantiles from lowest to highest. The lowest cIMT quartile was defined as having a mean cIMT < 588 µm, while the highest cIMT quartile was defined as having a mean cIMT > 748 µm. Specifically, the highest cIMT quantile group had a worse CVD risk factors profile compared to the lowest cIMT quantile group. It was found that, for every one SD increase in age and systolic blood pressure, the mean cIMT increased by 0.357 SD and 0.115 SD, respectively. CONCLUSION: Systolic blood pressure and age were the strongest independent risk factors for a high cIMT value compared to other risk factors.

Acetyl-L-Carnitine and Liposomal Co-Enzyme Q10 Attenuate Hepatic Inflammation, Apoptosis, and Fibrosis Induced by Propionic Acid.

Propionic acid (PRA) is a metabolic end-product of enteric bacteria in the gut, and it is commonly used as a food preservative. Despite the necessity of PRA for immunity in the body, excessive exposure to this product may result in disruptive effects. The purpose of this study is to examine the hepatoprotective effects of acetyl-L-carnitine (A-CAR) and liposomal-coenzyme Q10 (L-CoQ10) against PRA-induced injury. Liver injury in rats was induced by oral administration of PRA, and A-CAR and L-CoQ10 were administered concurrently with PRA for 5 days. Oxidative stress, inflammatory, apoptotic, and fibrotic biomarkers were analyzed; the histology of liver tissue was assessed as well to further explore any pathological alterations. PRA caused significant increases in the levels of serum liver enzymes and hepatic oxidative stress, inflammatory, and apoptotic biomarker levels, along with histopathological alterations. Concurrent treatment with A-CAR and/or L-CoQ10 with PRA prevented tissue injury and decreased the levels of oxidative stress, proinflammatory cytokines, and apoptotic markers. Additionally, A-CAR and/or L-CoQ10 modulated the expression of high-mobility group box-1, cytokeratin-18, transforming growth factor-beta1, and SMAD3 in liver tissue. In conclusion, A-CAR and/or L-CoQ10 showed hepatoprotective efficacy by reducing oxidative stress, the inflammatory response, apoptosis, and fibrosis in liver tissue.

Cross-Regulation between Autophagy and Apoptosis Induced by Vitamin E and Lactobacillus Plantarum through Beclin-1 Network.

Autophagy and apoptosis are two important regulatory mechanisms for how the body can respond to diseases. This study was designed to investigate the protective actions of vitamin E (Vit-E) and lactobacillus plantarum (Lac-B) against mercuric chloride (HgCl2)-induced kidney injury. Thirty albino rats were divided into five groups: group 1 served as the normal group; rats in group 2 received high doses of HgCl2; rats in groups 3, 4 and 5 were given Vit-E, Lac-B and the combination of Vit-E and Lac-B, respectively along with HgCl2 for two weeks. HgCl2 provoked renal injury, manifested by elevation in serum urea, urea nitrogen and creatinine. Kidney levels of oxidative stress and inflammation were markedly increased post HgCl2 administration. Moreover, HgCl2 significantly elevated the gene expression levels of VCAM-1 and cystatin C, while podocin was downregulated. Additionally, it markedly decreased the protein expression of Beclin-1 and Bcl-2. Histopathological examination revealed massive degeneration with congested blood vessels following HgCl2 administration. Treatment with Vit-E or/and Lac-B restored the normal levels of the previously mentioned parameters, as well as improved the morphology of kidney tissues. Both Vit-E and Lac-B provided a protective effect against HgCl2-induced kidney damage by regulating autophagy and apoptosis.

Acetyl-L-carnitine and/or liposomal co-enzyme Q10 prevent propionic acid-induced neurotoxicity by modulating oxidative tissue injury, inflammation, and ALDH1A1-RA-RARα signaling in rats.

Propionic acid (PPA) is a short-chain fatty acid produced endogenously by gut microbiota and found in foodstuffs and pharmaceutical products as an additive. Exposure to PPA has been associated with the development of autism spectrum disorder (ASD). The purpose of this study was to investigate the protective effect of acetyl-L-carnitine (ALCAR) and liposomal Co-enzyme Q10 (CoQ10) against cerebral and cerebellar oxidative injury, inflammation, and cell death, and alterations in ALDH1A1-RA-RARα signaling in an autism-like rat model induced by PPA. The rats were treated with PPA and concurrently received ALCAR and/or CoQ10 for 5 days. The animals were sacrificed, and the cerebral cortex and cerebellum were collected for analysis. PPA caused histopathological alterations along with increased malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 in the cerebrum and cerebellum of rats. Reduced glutathione (GSH) and antioxidant enzymes were declined in the brain of rats that received PPA. Concurrent treatment with ALCAR and/or CoQ10 prevented tissue injury, decreased MDA, NF-κB p65, and pro-inflammatory cytokines, and enhanced cellular antioxidants in PPA-administered rats. ALCAR and/or CoQ10 upregulated Bcl-2 and decreased Bax and caspase-3 in the brain of rats. In addition, ALCAR and/or CoQ10 upregulated cerebral and cerebellar ALDH1A1 and RARα in PPA-treated rats. The combination of ALCAR and CoQ10 showed more potent effects when compared with the individual treatments. In conclusion, ALCAR and/or CoQ10 prevented tissue injury, ameliorated oxidative stress, inflammatory response, and apoptosis, and upregulated ALDH1A1-RA-RARα signaling in the brain of autistic rats.

Nano-Curcumin Prevents Copper Reproductive Toxicity by Attenuating Oxidative Stress and Inflammation and Improving Nrf2/HO-1 Signaling and Pituitary-Gonadal Axis in Male Rats.

Copper is essential for several cellular processes and is an important catalytic factor for many proteins. However, excess copper can provoke oxidative stress and reproductive toxicity. This study evaluated the effect of liposomal nano-curcumin (N-CUR) and CUR on testicular oxidative injury, inflammation, and apoptosis, and altered steroidogenesis and Nrf2/HO-1 signaling induced by copper sulfate (CuSO4). Rats received CuSO4 and N-CUR or CUR via oral gavage for 7 days. CuSO4 induced histopathological changes and altered pituitary-gonadal axis manifested by decreased serum gonadotropins and testosterone. Testicular steroidogenesis genes (StAR, 3ß-HSD, CYP17A1, and 17ß-HSD) and androgen receptor (AR) were downregulated in rats that received CuSO4. N-CUR and CUR prevented testicular tissue injury, increased circulating FSH, LH, and testosterone, and upregulated testicular steroidogenesis genes and AR. Additionally, N-CUR and CUR decreased testicular MDA, NO, NF-κB, iNOS, TNF-α, Bax, and caspase-3 while enhanced Bcl-2, Nrf2, and the antioxidants GSH, HO-1, SOD, and catalase. In conclusion, N-CUR and CUR prevented CuSO4-induced reproductive toxicity in male rats by suppressing oxidative injury and inflammatory response and boosting steroidogenesis, sex hormones, and Nrf2/HO-1 signaling. N-CUR was more effective in ameliorating tissue injury, oxidative stress, inflammation, and apoptosis and enhancing steroidogenesis and Nrf2/HO-1 than the native form.

Transdermal Glipizide Delivery System Based on Chitosan-Coated Deformable Liposomes: Development, Ex Vivo, and In Vivo Studies.

The current study aimed to develop and evaluate a sustained-release transdermal Glipizide (GLP) film to overcome its oral administration problems. Chitosan (CS)-coated deformable liposomes (DLs) were utilized to enhance the drug transdermal delivery. The formulations were characterized in terms of particle size, zeta potential, entrapment efficiency (EE%), vesicle deformability, morphology, stability, and in vitro release. Transdermal films of chosen formulations were prepared by the solvent casting technique, and an ex vivo study throughout rat skin was also performed. Moreover, a pharmacokinetics (PK) study was carried out and blood glucose levels were estimated. All the liposomes were in the nanometer range and a high EE% was obtained from DLs compared to conventional liposomes (CL). The prepared formulations showed a high stability and the DLs exhibited a high deformability compared to CL. The in vitro release study confirmed the sustained release of GLP from both CL and DL and a more pronounced sustained release of GLP was detected after coating with CS. Moreover, GLP was shown to efficiently permeate through the rat skin from transdermal films by an ex vivo permeation test. The transdermal films showed a promising PK profile in the rat as compared with oral GLP. Most importantly, GLP-CS-DL1 demonstrated a higher hypoglycemic effect, confirming the possibility of systemic action by the local topical delivery of GLP.

A promising antifibrotic drug, pyridoxamine attenuates thioacetamide-induced liver fibrosis by combating oxidative stress, advanced glycation end products, and balancing matrix metalloproteinases.

Liver fibrosis is a common chronic hepatic disease. This study was done to examine the effect of pyridoxamine against thioacetamide-induced hepatic fibrosis. Animals were divided into four groups (1) control group; (2) Thioacetamide group (200 mg/kg, i.p.) twice a week for eight weeks; (3) Pyridoxamine-treated group treated with pyridoxamine (100 mg/kg/day, i.p.) for eight weeks; (4) Thioacetamide and pyridoxamine group, in which pyridoxamine was given (100 mg/kg/day, i.p.) during thioacetamide injections. Thioacetamide treatment resulted in hepatic dysfunction manifested by increased serum levels of bilirubin, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Oxidative stress was noted by increased hepatic lipid peroxidation and decreased glutathione (GSH). Increased concentrations of total nitrite/nitrate, advanced glycation end products (AGEs), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), matrix metalloproteinases (MMP-2&9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were noticed in hepatic tissues. Immunostaining sections also revealed overexpression of MMP-2, MMP-9 and collagen IV. Liver fibrosis was confirmed by severe histopathological changes. Pyridoxamine improved the assessed parameters. Moreover, histopathological and immunohistological studies supported the ability of pyridoxamine to reduce liver fibrosis. The findings of the present study provide evidence that pyridoxamine is a novel target for the treatment of liver fibrosis.

Nano-Resveratrol: A Promising Candidate for the Treatment of Renal Toxicity Induced by Doxorubicin in Rats Through Modulation of Beclin-1 and mTOR.

Background: Although doxorubicin (DXR) is one of the most used anticancer drugs, it can cause life-threatening renal damage. There has been no effective treatment for DXR-induced renal damage until now. Aim: This work aims at examining the potential impact of nano-resveratrol (N-Resv), native resveratrol (Resv), and their combination with carvedilol (Card) against DXR-induced renal toxicity in rats and to investigate the mechanisms through which these antioxidants act to ameliorate DXR nephrotoxicity. Method: DXR was administered to rats (2 mg/kg, i.p.) twice weekly over 5 weeks. The antioxidants in question were taken 1 week before the DXR dose for 6 weeks. Results: DXR exhibited an elevation in serum urea, creatinine, renal lipid peroxide levels, endoglin expression, kidney injury molecule-1 (KIM-1), and beclin-1. On the other hand, renal podocin and mTOR expression and GSH levels were declined. In addition, DNA fragmentation was markedly increased in the DXR-administered group. Treatment with either Resv or N-Resv alone or in combination with Card ameliorated the previously measured parameters. Conclusion: N-Resv showed superior effectiveness relative to Resv in most of the measured parameters. Histopathological examination revealed amelioration of renal structural and cellular changes after DXR by Card and N-Resv, thus validating the previous biochemical and molecular results.

The beneficial effects of antioxidants combination on cardiac injury induced by tetrachloromethane.

The purpose of this research was to evaluate the efficacy of carsil (CAR) either alone or in combination with α-tocopherol (α-TOCO) and/or turmeric (TUMR) against tetrachloromethane (TCM)-induced cardiomyocyte injury in rats. Administration of CAR either alone or in combination with α-TOCO and/or TUMR post-TCM injection, significantly mitigated the increases in serum troponin T, creatine kinase-MB (CK-MB) as well as interleukin-6 (IL-6), interferon γ (IFN-γ), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP). They also decline the elevation of caspase-3, vascular endothelial growth factor (VEGF) protein expression as well as DNA damage in cardiac tissues induced by TCM. The biochemical results were confirmed by histopathological investigation. Conclusion: The combination of the three antioxidants showed greater cardioprotective potential, compared to individual drugs. Therefore, this combination may be recommended as a complementary therapy to antagonize cardiac injury induced by different insults.

L-Ascorbic Acid and Curcumin Prevents Brain Damage Induced via Lead Acetate in Rats: Possible Mechanisms.

Lead acetate (lead ac.) is a widespread ecological toxicant that can cause marked neurotoxicity and decline in brain functions. This study aimed to evaluate the possible neuroprotective role of L-ascorbic acid (ASCR) and curcumin (CRCM) alone or together against lead ac.-induced neurotoxicity. Rats were injected with lead ac. then treated orally with ASCR and CRCM alone or in combination for 7 days. Lead ac. caused elevation in brain tumor necrosis factor-α, interleukin-6, caspase-3, and malondialdehyde levels, while superoxide dismutase, reduced glutathione as well as the expression of brain-derived neurotrophic factor, cAMP response element-binding, and Beclin1 were downregulated. Expressions of C/EBP homologous protein and mammalian Target of rapamycin kinase were upregulated in brain tissues matched with the control group. Histopathological examination supported the previously mentioned parameters, the administration of the antioxidants in question modulated all the altered previous parameters. The combination regimen achieved the superlative results in the antagonizing lead ac.-induced neurotoxicity via its antioxidant and antiapoptotic activities.

Curcumin and Nano-Curcumin Mitigate Copper Neurotoxicity by Modulating Oxidative Stress, Inflammation, and Akt/GSK-3ß Signaling.

Copper (Cu) is essential for multiple biochemical processes, and copper sulphate (CuSO4) is a pesticide used for repelling pests. Accidental or intentional intoxication can induce multiorgan toxicity and could be fatal. Curcumin (CUR) is a potent antioxidant, but its poor systemic bioavailability is the main drawback in its therapeutic uses. This study investigated the protective effect of CUR and N-CUR on CuSO4-induced cerebral oxidative stress, inflammation, and apoptosis in rats, pointing to the possible involvement of Akt/GSK-3ß. Rats received 100 mg/kg CuSO4 and were concurrently treated with CUR or N-CUR for 7 days. Cu-administered rats exhibited a remarkable increase in cerebral malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 associated with decreased GSH, SOD, and catalase. Cu provoked DNA fragmentation, upregulated BAX, caspase-3, and p53, and decreased BCL-2 in the brain of rats. N-CUR and CUR ameliorated MDA, NF-κB p65, and pro-inflammatory cytokines, downregulated pro-apoptotic genes, upregulated BCL-2, and enhanced antioxidants and DNA integrity. In addition, both N-CUR and CUR increased AKT Ser473 and GSK-3ß Ser9 phosphorylation in the brain of Cu-administered rats. In conclusion, N-CUR and CUR prevent Cu neurotoxicity by attenuating oxidative injury, inflammatory response, and apoptosis and upregulating AKT/GSK-3ß signaling. The neuroprotective effect of N-CUR was more potent than CUR.