Gallic acid supplementation partially ameliorates reproductive aging in rooster breeders by improving semen quality, sperm kinetics, hormones, and antioxidant status.

Aging leads to decreased fertility in roosters, which is likely due to increased oxidative stress. This study evaluated the antioxidant effects of gallic acid (GA) supplementation on sperm quality and fertility of aged roosters. This study evaluated whether GA supplementation can mitigate age-related fertility decline. Roosters were randomly assigned to: control, 100 mg/kg GA, or 200 mg/kg GA. Semen parameters, sperm kinetics, hormone levels, fertility rate, and hatchability were assessed. GA increased semen concentration, membrane integrity and viability while decreasing defects versus control (P < 0.01). Testosterone was higher in GA groups (P<0.01) without affecting gonadotropins. Furthermore, 200 mg/kg GA optimized motility, velocity, linearity, and beat cross frequency versus control and 100 mg/kg GA (P < 0.01). Fertility and hatchability were higher in both GA groups. In conclusion, GA supplementation in aged roosters improves sperm quality, antioxidant status, testosterone, and fertility outcomes, likely by mitigating oxidative stress. The 200 mg/kg dose elicited optimal effects on motion parameters.

Gallic acid attenuates torsion/detorsion-induced testicular injury in rats through suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress.

It was aimed to evaluate whether gallic acid (GA) have a beneficial effect in the testicular ischemia/reperfusion injury (IRI) model in rats for the first time. Testicular malondialdehyde, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, catalase, high mobility group box 1 protein, nuclear factor kappa B, tumor necrosis factoralpha, interleukin-6, myeloperoxidase, 78-kDa glucose-regulated protein, activating transcription factor 6, CCAAT-enhancer-binding protein homologous protein and caspase-3 levels were determined using colorimetric methods. The oxidative stress, inflammation, endoplasmic reticulum stress and apoptosis levels increased statistically significantly in the IRI group compared with the sham operated group (p < 0.05). GA application improved these damage significantly (p < 0.05). Moreover, it was found that the results of histological examinations supported the biochemical results to a statistically significant extent. Our findings suggested that GA may be evaluated as a protective agent against testicular IRI.

Combined administration of gallic acid and glibenclamide mitigate systemic complication and histological changes in the cornea of diabetic rats induced with streptozotocin

Purpose: To determine the effect of gallic acid or its combination with glibenclamide on some biochemical markers and histology of the cornea of streptozotocin (STZ) induced diabetic rats. Methods: Following induction of diabetes, 24 male albino rats were divided into four groups of six rats each. Groups 1 and 2 (control and diabetic) received rat pellets and distilled water; group 3 (gallic acid) received rat pellets and gallic acid (10 mg/kg, orally) dissolved in the distilled water; and group 4 (gallic acid + glibenclamide) received rat pellets, gallic acid (10 mg/kg, orally), and glibenclamide (5 mg/kg, orally) dissolved in the distilled water. The treatments were administered for three months after which the rats were sacrificed after an overnight fast. Blood and sera were collected for the determination of biochemical parameters, while their eyes were excised for histology. Results: STZ administration to the rats induced insulin resistance, hyperglycemia, microprotenuria, loss of weight, oxidative stress, inflammation, and alteration of their cornea histology, which was abolished following supplementation with gallic acid or its combination with glibenclamide. Conclusions: The study showed the potentials of gallic acid and glibenclamide in mitigating systemic complication and histological changes in the cornea of diabetic rats induced with STZ.

An UHPLC/LC-MS illustrated the dynamic profiling of balanophorin B, gallic acid, and 4-hydroxycinnamic acid in rat as 3 molecular entities from Balanophora simaoensis.

An UHPLC/LC-MS was founded to detect balanophorin B (B), gallic acid (GA), 4-hydroxycinnamic acid (HC), and their in vivo profiling in rats, after oral administration of the ethanol extract of Balanophora simaoensis S. Y. Chang et Tam. The in vivo dynamic existence of 3 molecular entities in rats and the multistep biotransformation of GA were elucidated by their sensitive mass spectrometry response after efficient UHPLC and/or HPLC separation, through analyzing the bio-samples of rat plasma, bile, liver, kidneys, and excreta. The method was validated with satisfactory calibration curves having correlation coefficients r from 0.996 to 0.999 for concentration scaled from 0.100 nM to 0.100 µM, internal standard normalized matrix factors ranged from 0.923 to 0.993, sextuplicate recoveries valued from 95.0% to 103.6%, as well as accuracy and precision varied from 95.6% to 103.7%. The content of B, GA, and HC in the whole herb was of 4.66, 63.5, and 10.4 µmol/kg in dry weight, respectively. The Cmax for B, GA, and HC in rat systemic circulation was of 76.0 nM, 2.30 µM, and 51.0 µM, with tmax at 3, 2, and 2 h, respectively. B and GA stayed in rat liver over 4 hs to present a material base for the pharmacology and pharmacodynamics of the whole herb. The biotransformation of GA indicated a complicated scheme in rats. As a final metabolite from GA with total biotransformation conversion over 20%, 4-hydroxybenzaldehyde resourced from two steps of dehydroxylation and one step of reduction of GA, but not concerned with HC.

Gallic acid for cancer therapy: Molecular mechanisms and boosting efficacy by nanoscopical delivery.

Cancer is the second leading cause of death worldwide. Majority of recent research efforts in the field aim to address why cancer resistance to therapy develops and how to overcome or prevent it. In line with this, novel anti-cancer compounds are desperately needed for chemoresistant cancer cells. Phytochemicals, in view of their pharmacological activities and capacity to target various molecular pathways, are of great interest in the development of therapeutics against cancer. Plant-derived-natural products have poor bioavailability which restricts their anti-tumor activity. Gallic acid (GA) is a phenolic acid exclusively found in natural sources such as gallnut, sumac, tea leaves, and oak bark. In this review, we report on the most recent research related to anti-tumor activities of GA in various cancers with a focus on its underlying molecular mechanisms and cellular pathwaysthat that lead to apoptosis and migration of cancer cells. GA down-regulates the expression of molecular pathways involved in cancer progression such as PI3K/Akt. The co-administration of GA with chemotherapeutic agents shows improvements in suppressing cancer malignancy. Various nano-vehicles such as organic- and inorganic nano-materials have been developed for targeted delivery of GA at the tumor site. Here, we suggest that nano-vehicles improve GA bioavailability and its ability for tumor suppression.

Intratumoral synthesis of nano-metalchelate for tumor catalytic therapy by ligand field-enhanced coordination.

The iron gall ink-triggered chemical corrosion of hand-written documents is a big threat to Western cultural heritages, which was demonstrated to result from the iron gall (GA-Fe) chelate-promoted reactive oxygen species generation. Such a phenomenon has inspired us to apply the pro-oxidative mechanism of GA-Fe to anticancer therapy. In this work, we construct a composite cancer nanomedicine by loading gallate into a Fe-engineered mesoporous silica nanocarrier, which can degrade in acidic tumor to release the doped Fe3+ and the loaded gallate, forming GA-Fe nanocomplex in situ. The nanocomplex with a highly reductive ligand field can promote oxygen reduction reactions generating hydrogen peroxide. Moreover, the resultant two-electron oxidation form of GA-Fe is an excellent Fenton-like agent that can catalyze hydrogen peroxide decomposition into hydroxyl radical, finally triggering severe oxidative damage to tumors. Such a therapeutic approach by intratumoral synthesis of GA-Fe nano-metalchelate may be instructive to future anticancer researches.

Chemoprotective Effect of Syringic Acid on Cyclophosphamide Induced Ovarian Damage via Inflammatory Pathway.

Cyclophosphamide (CP) is very well-known anticancer drug and commonly used against various cancers. CP therapy is related to female ovarian cancer and causes female infertility. The ovarian cancer associated with the increase oxidative stress and inflammatory reaction. Syringic acid (SA) is very well phyto-constituent and already proof antioxidant and anti-inflammatory effects on various diseases. We investigated the chemoprotective impact of SA on CP mediated ovarian damage, and the underlying mechanism. CP (75 mg/kg) was used to cause ovarian damage and rats were randomly divided into separate groups and received a different dose of SA for 14-day. Body weight, food and water intake were determined. Ovarian weight and tumor index was measured. Antioxidant parameters were determined in the serum and ovarian tissue. Pro-inflammatory cytokines, apoptosis parameters and inflammatory mediators were estimated in the serum. Hormonal parameters and Histomorphometry were estimated. Dose dependently treatment of SA significantly (p < 0.001) decreased the levels of biochemical parameter such as nitric oxide (NO), myeloperoxidase (MPO) and augmented the antioxidant parameters include catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and reduced malondialdehyde (MDA) level in serum and ovarian tissue. SA treatment significantly (p < 0.001) suppressed the level of luteinizing hormones (LH), anti-mullerian hormone (AMH), estradiol (E2) and folliclestimulating hormone (FSH) as well as ovarian follicles. SA significantly (p < 0.001) down-regulated cytokines, inflammatory mediator and caspase-3 parameters. Taken altogether, we conclude that SA considerably reduced ovarian damage via reduced oxidative stress and inflammatory reaction.

The benzoate plant metabolite ethyl gallate prevents cellular- and vascular-lipid accumulation in experimental models of atherosclerosis.

Ethyl gallate (EG) is a well-known constituent of medicinal plants, but its effects on atherosclerosis development are not clear. In the present study, the anti-atherosclerosis effects of EG and the underlying mechanisms were explored using macrophage cultures, zebrafish and apolipoprotein (apo) E deficient mice. Treatment of macrophages with EG (20 µM) enhanced cellular cholesterol efflux to HDL, and reduced net lipid accumulation in response to oxidized LDL. Secretion of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) from activated macrophages was also blunted by EG. Fluorescence imaging techniques revealed EG feeding of zebrafish reduced vascular lipid accumulation and inflammatory responses in vivo. Similar results were obtained in apoE-/- mice 6.5 months of age, where plaque lesions and monocyte infiltration into the artery wall were reduced by 70% and 42%, respectively, after just 6 weeks of injections with EG (20 mg/kg). HDL-cholesterol increased 2-fold, serum cholesterol efflux capacity increased by ∼30%, and the levels of MCP-1 and IL-6 were reduced with EG treatment of mice. These results suggest EG impedes early atherosclerosis development by reducing the lipid and macrophage-content of plaque. Underlying mechanisms appeared to involve HDL cholesterol efflux mechanisms and suppression of pro-inflammatory cytokine secretion.

Improved Oral Bioavailability and Hypolipidemic Effect of Syringic Acid via a Self-microemulsifying Drug Delivery System.

This study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the solubility, oral bioavailability, and hypolipidemic effects of syringic acid (SA), a bioactive and poorly-soluble polyphenol. Based on the response surface methodology-central composite design (RSM-CCD), an optimum formulation of SA-SMEDDS, consisting of ethyl oleate (oil, 12.30%), Cremophor-EL (surfactant, 66.25%), 1,2-propanediol (cosurfactant, 21.44%), and drug loading (50 mg/g), was obtained. The droplets of SA-SMEDDS were nanosized (16.38 ± 0.12 nm), spherically shaped, and homogeneously distributed (PDI = 0.058 ± 0.013) nanoparticles with high encapsulation efficiency (98.04 ± 1.39%) and stability. In vitro release study demonstrated a prolonged and controlled release of SA from SMEDDS. In vitro cell studies signified that SA-SMEDDS droplets substantially promoted cellular internalization. In comparison with the SA suspension, SA-SMEDDS showed significant prolonged Tmax, t1/2, and MRT after oral administration. Also, SA-SMEDDS exhibited a delayed in vivo elimination, increased bioavailability (2.1-fold), and enhanced liver accumulation. Furthermore, SA-SMEDDS demonstrated significant improvement in alleviating serum lipid profiles and hepatic steatosis in high-fat diet-induced hyperlipidemia in mice. Collectively, SMEDDS demonstrated potential as a nanosystem for the oral delivery of SA with enhanced bioavailability and hypolipidemic effects.

Effect of gallic acid on the larvae of Spodoptera litura and its parasitoid Bracon hebetor.

The antibiosis effect of gallic acid on Spodoptera litura F. (Lepidoptera: Noctuidae) and its parasitoid evaluated by feeding six days old larvae on artificial diet incorporated with different concentrations (5 ppm, 25 ppm, 125 ppm, 625 ppm, 3125 ppm) of the phenolic compound revealed higher concentration (LC50) of gallic acid had a negative impact on the survival and physiology of S. litura and its parasitoid Bracon hebetor (Say) (Hymenoptera:Braconidae). The mortality of S. litura larvae was increased whereas adult emergence declined with increasing concentration of gallic acid. The developmental period was delayed significantly and all the nutritional indices were reduced significantly with increase in concentration. Higher concentration (LC50) of gallic acid adversely affected egg hatching, larval mortality, adult emergence and total development period of B. hebetor. At lower concentration (LC30) the effect on B. hebetor adults and larvae was non-significant with respect to control. Gene expression for the enzymes viz., Superoxide dismutase, Glutathione peroxidase, Peroxidase, Esterases and Glutathione S transferases increased while the total hemocyte count of S. litura larvae decreased with treatment. Our findings suggest that gallic acid even at lower concentration (LC30) can impair the growth of S. litura larvae without causing any significant harm to its parasitoid B. hebetor and has immense potential to be used as biopesticides.

Gallic acid ameliorates sodium arsenite-induced renal and hepatic toxicity in rats.

Chronic exposure to toxic inorganic arsenic results in the adverse health effects including skin lesions, cardiovascular diseases, diabetes, neurological disorders, and liver and kidney diseases. Gallic acid (GA) is an important phenolic compound, which could protect different tissues from oxidative stress induced damage. The present study investigated effects of GA against sodium arsenite (SA)-induced renal and hepatic toxicity. Thirty-five rats were randomly divided in to five groups; group 1 was treated with normal saline (2 ml/kg/day, p.o.; for 21 days); group 2 was exposed to SA (10 mg/kg/day, p.o.; for 14 days); groups 3 and 4 were treated with GA (10 and 30 mg/kg/day, respectively; for 7 days) prior to exposure to SA, and treatment was continued up to 21 days in parallel with SA administration; group 5 was treated with GA (30 mg/kg/day, p.o.; for 21 days). The level of MDA, IL-1ß, NO and glutathione (GSH) and the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were evaluated in kidney and liver tissues. Histopathological parameters and serum levels of ALT, AST, ALP, Cr and BUN were also assessed. Treatment with GA remarkably improved SA-induced alteration of hematological and histopathological parameters; these protective effects were associated with the reduction of SA-induced elevation of MDA, IL-1ß and NO levels as well as reduction of GSH level and GPx, SOD and CAT activity. Our results suggest that GA may inhibit SA-induced kidney and liver toxicity through scavenging reactive free radicals and increasing intracellular antioxidant capacity.

Breast Cancer Resistance Protein and Multidrug Resistance Protein 2 Mediate the Disposition of Leonurine-10-O-ß-glucuronide.

BACKGROUND: Leonurine (Leo), a promising antilipemic agent that has been approved for clinical trials, is extensively metabolized into bioactive Leonurine-10-O-ß-glucuronide (L-10-G) vivo. OBJECTIVE: To explore the effects of breast cancer resistance protein (Bcrp) and multidrug resistance protein 2 (Mrp2) on the disposition of L-10-G. METHODS: The pharmacokinetics, tissue distribution and intestinal perfusion of Leo were studied by using efflux transporter gene knockout mouse models. The enzyme kinetics via liver and intestinal microsomes were also examined. RESULTS: After intravenous injection with Leo, the AUC0-∞ values of L-10-G in Bcrp1-/- and Mrp2-/- mice were 1.55-fold and 16.80-fold higher, respectively, than those in wild-type FVB mice (P < 0.05). After oral administration, the AUC0-∞ value of L-10-G showed a 2.82-fold increase in Mrp2-/- mice compared with wild-type FVB mice (P < 0.05). After gavage with Leo for 10 and 25 min, the bile accumulation of L-10-G in Mrp2-/- mice was 3-fold and 22-fold lower, respectively, than that in wild-type FVB mice (P < 0.05). Besides, the intestinal excreted amount of L-10-G showed 2.22-fold and 2.68-fold decrease in Bcrp1-/- and Mrp2-/- mice, respectively, compared with that in wild-type FVB mice (P < 0.05). The clearance of L-10-G decreased in liver microsomes and increased in intestinal microsomes of Bcrp1-/- and Mrp2-/- mice compared to the wild-type FVB mice (P < 0.05). CONCLUSION: Both Bcrp and Mrp2 are involved in the disposition of L-10-G, and Mrp2 exhibits a superior influence.

Therapeutic Potential of Zinc Oxide-Loaded Syringic Acid Against in vitro and in vivo Model of Lung Cancer.

INTRODUCTION: Lung cancer is one of the most aggressive forms of cancer that leads to a high mortality rate amongst several cancer types and it is a widely recurrent cancer globally. The use of zinc oxide nanoparticles (ZnONPs) in the formulation of sun cream, food flavors, and colorings due to its varied biological properties. The extensive significance of nanoparticles encourages their production but the approaches are a common challenge in concluding the direct beneficial effect for the disease treatment. Hence, in the present study, zinc oxide-loaded syringic acid (ZnO-SYR) phytochemical was used to elucidate the therapeutic effect against lung cancer. METHODS: The ZnO-SYR nanoparticles were synthesized and characterized by UV-visible spectroscopy, X-ray diffraction, dynamic light scattering, and FT-IR analysis. The characterized ZnO-SYR was tested on in vivo mouse model of lung cancer (benzo(a)pyrene (BAP)) and in vitro A549 cells. RESULTS: The results demonstrated the significant restoration of body weight with attenuated serum marker enzymes compared to BAP-treated animals. In addition, cytokine estimation revealed ameliorated levels of TNF-α, interleukins, IL-6, IL-1ß with evidenced histological observations in ZnO-SYR-treated mice compared to BAP-induced lung cancer mice. DISCUSSION: Furthermore, cytotoxicity analysis demonstrated the altered mitochondrial membrane potential (MMP), with a profound increase in reactive oxygen species (ROS) levels, and apoptosis mechanism by ZnO-SYR compared to control cells. The conclusions of the present study put forward an evident confirmation of the protective and beneficial effects of zincoxide-loaded syringic acid against the BAP-induced lung cancer model.

Gallic and butyric acids modulated NLRP3 inflammasome markers in a co-culture model of intestinal inflammation.

Bioactive compounds from food products made from natural ingredients such as corn and common bean could target the NLRP3 inflammasome, protein scaffolds with a key role in the moderation of intestinal inflammation. This research aimed to evaluate the anti-inflammatory effect from the fermented non-digestible fraction of baked corn and common bean snack (FNDF), and its main components, on the modulation of NLRP3 inflammasome markers in vitro. For this, a THP-1 macrophage/differentiated Caco-2 cell co-culture was used as a model of intestinal inflammation. A disease control (DC) (LPS/human IFN-γ, 10 ng/mL) was compared with FNDF (40-300 µg/mL) and its pure components: gallic (38.85 µM) and butyric acids (6 µM), verbascose (0.06 µM), their mixture, and an anti-inflammatory control (tofacitinib, 5 µM). Compared to DC, FNDF (40 µg/mL) reduced the 48 h-basolateral nitrites (40-60%), IL-1ß/IL-18, and TNF-α production. Additionally, it decreased the total reactive oxygen species (36.3%) and nitric oxide synthase (6.9%) activities, increasing superoxide dismutase (228.2%) activity. Compared to NLRP3 positive control, FNDF components decreased NLRP3 markers (caspase-1 activity, IL-1ß, and apoptosis). These results highlight NLRP3-anti-inflammatory effects from FNDF components. This is the first report of the NLRP3 inflammasome modulation by digested food matrix components, using a co-culture approach.

Impact of Reverse Micelle Loaded Lipid Nanocapsules on the Delivery of Gallic Acid into Activated Hepatic Stellate Cells: A Promising Therapeutic Approach for Hepatic Fibrosis.

PURPOSE: Gallic acid (GA) is a polyphenolic compound with proven efficacy against hepatic fibrosis in experimental animals. However, it suffers from poor bioavailability and rapid clearance that hinders its clinical investigation. Accordingly, we designed and optimized reverse micelle-loaded lipid nanocapsules (RMLNC) using Box-Behnken design that can deliver GA directly into activated-hepatic stellate cells (aHSCs) aiming to suppress hepatic fibrosis progression. METHODS: GA-RMLNC was prepared using soft energy, solvent free phase inversion temperature method. Effects of formulation variables on particle size, zeta potential, entrapment efficiency (EE%) and GA release were studied. In-vivo biodistribution of GA-RMLNC in rats and in-vitro activities on aHSCs were also explored. RESULTS: Nano-sized GA-RMLNCs (30.35 ± 2.34 nm) were formulated with high GA-EE% (63.95 ± 2.98% w/w) and physical stability (9 months). The formulated system showed burst GA release in the first 2 h followed by sustained release profile. In-vivo biodistribution imaging revealed that RMLNC-loaded with rhodamine-B accumulated mainly in rats' livers. Relative to GA; GA-RMLNC displayed higher anti-proliferative activities, effective internalization into aHSCs, marked down-regulation in pro-fibrogenic biomarkers' expressions and elevated HSCs' apoptosis. CONCLUSIONS: These findings emphasize the promising application of RMLNC as a delivery system in hepatic fibrosis treatment, where successful delivery of GA into aHSCs was ensured via increased cellular uptake and antifibrotic activities.

Toxicological implications of amplifying the antibacterial activity of gallic acid by immobilisation on silica particles: A study on C. elegans.

Immobilisation of natural compounds on solid supports to amplify antimicrobial properties has reported successful results, but modifications to physico-chemical properties can also imply modifications from a toxicological viewpoint. This work aimed to study the immobilising process of gallic acid in the antibacterial activity of L. innocua and its toxicological properties in vivo using Caenorhabditis elegans. The experiment was based on obtaining the minimum bactericidal concentration for free and immobilised gallic acid by comparing lethality, locomotion behaviour, chemotaxis and thermal stress resistance on C.elegans at those concentrations. The results showed a lowering minimum bactericidal concentration and modifications to nematode responses. Increased lethality and velocity of movements was observed. Immobilisation increased the repellent effect of gallic acid with a negative chemotaxis index. Thermal stress resistance was also affected, with higher mortality for immobilised gallic acid compared to bare particles and free gallic acid. Thus despite evidencing a generalised increase in the toxicity of gallic acid in vivo, lowering the minimum bactericidal concentration allowed a bacterial reduction of 99 % with less than one third of mortality for the nematodes exposed to free gallic acid.

Protective effect of gallic acid and gallic acid-loaded Eudragit-RS 100 nanoparticles on cisplatin-induced mitochondrial dysfunction and inflammation in rat kidney.

Cisplatin is used as a chemotherapy drug in the treatment of various types of cancer. Mitochondrial dysfunction, oxidative stress and inflammation have been identified as major mechanisms of cisplatin nephrotoxicity. The present study investigated the protective effects of pure gallic acid and nanoparticle gallic acid nanoparticles (nano-gallic acid) on cisplatin induced nephrotoxicity. Nano-gallic acid was prepared by double emulsions-solvent evaporation technique using Eudragit RS 100 polymer and polyvinyl alcohol as carrier. Then, the physicochemical characterization of the nanoparticles was examined. In the present study, renal mitochondria were isolated using different centrifugal methods. Our data indicated that the doses of 50 and 100 mg/kg gallic acid and 10 mg/kg nano-gallic acid significantly decreased mitochondrial reactive oxygen species (ROS) formation, mitochondrial membrane damage (ΔΨm), mitochondrial malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and significantly increased mitochondrial glutathione (GSH), mitochondrial superoxide dismutase (MnSOD), mitochondrial glutathione peroxidase (GPX) and mitochondrial catalase compared to the cisplatin treated group. Histopathological studies also confirmed biochemical tests. Finally, our results confirmed that the pure gallic acid and its nanoparticle improved renal oxidative stress, inflammation and mitochondrial dysfunction in acute nephrotoxicity induced by cisplatin in rat. Nano-gallic acid (10 mg/kg) was selected as the most effective dose. The findings of this study showed the superiority of nano-gallic acid against pure gallic acid. In conclusion, nano-gallic acid-loaded Eudragit-RS 100 as a novel antioxidant can be considered in the treatment of renal complications of cisplatin.

Chronic exposure of adult male Wistar rats to bisphenol A causes testicular oxidative stress: Role of gallic acid.

OBJECTIVES: Bisphenol A (BPA) has been reported that among other male reproductive dys-functions, it can cause marked estrogenic effects including alteration in serum hormones as well as testicular lesions in exposed animals. This work sought to study the role of gallic acid (GA), a known antioxidant, on the BPA-induced testicular oxidative stress in adult male Wistar rats using serum hormone analysis, histopathology, and biochemical assays. METHODS: Adult male rats were divided into four groups (n=10) including control (0.2 ml of corn oil), GA (20 mg/kg/day), BPA (10 mg/kg/day), BPA+GA (BPA, 10 mg/kg/day + GA, 20 mg/kg/day). All medications were given by oral gavage for 45 consecutive days. The body and testicular weights were measured. Blood and organ samples were collected for the serum hormonal assay: testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL), and tissue biochemistry analysis: superoxide dismutase (SOD), reduced glutathione (GSH), glutathione-S-transferase (GST), malondialdehyde (MDA), hydrogen peroxide (H2O2), respectively. RESULTS: The BPA-treated rats showed significant reduction in the gonadosomatic index. BPA also caused significant decrease in the levels of the serum testosterone and prolactin. Furthermore, BPA induced testicular oxidative stress by decreasing the activities of antioxidant enzymes and increasing reactive oxygen species. However, co-treatment with GA protected against these alterations. CONCLUSION: Findings from the present study confirmed the previously reported data and show that the ability of GA, as a potent antioxidant, may protect against BPA-induced alterations in the male reproductive function. Hence, GA protects against testicular oxidative stress in adult male Wistar rats following chronic exposure to BPA.

SG-SP1 Suppresses Mast Cell-Mediated Allergic Inflammation via Inhibition of FcεRI Signaling.

Background: As the number of allergic disease increases, studies to identify new treatments take on new urgency. Epigallocatechin gallate (EGCG), a major component of green tea, has been shown to possess a wide range of pharmacological properties, including anti-inflammation and anti-viral infection. In previous study, gallic acid (GA), a part of EGCG, has shown anti-allergic inflammatory effect. To improve on preliminary evidence that GA has allergy mitigating effect, we designed SG-SP1 based on GA, and aimed to assess the effects of SG-SP1 on mast cell-mediated allergic inflammation using various animal and in vitro models. Methods: For in vitro experiments, various types of IgE-stimulated mast cells (RBL-2H3: mast cell-like basophilic leukemia cells, and primary cultured peritoneal and bone marrow-derived mast cells) were used to determine the role of SG-SP1 (0.1-1 nM). Immunoglobulin (Ig) E-induced passive cutaneous anaphylaxis and ovalbumin-induced systemic anaphylaxis, standard animal models for immediate-type hypersensitivity were also used. Results: For in vitro, SG-SP1 reduced degranulation of mast cells by down-regulating intracellular calcium levels in a concentration-dependent manner. SG-SP1 decreased expression and secretion of inflammatory cytokines in activated mast cells. This suppressive effect was associated with inhibition of the phosphorylation of Lyn, Syk and Akt, and the nuclear translocation of nuclear factor-κB. Due to the strong inhibitory effect of SG-SP1 on Lyn, the known upstream signaling to FcεRI-dependent pathway, we confirmed the direct binding of SG-SP1 to FcεRI, a high affinity IgE receptor by surface plasmon resonance experiment. Oral administration of SG-SP1 hindered allergic symptoms of both anaphylaxis models evidenced by reduction of hypothermia, serum IgE, ear thickness, and tissue pigmentation. This inhibition was mediated by the reductions in serum histamine and interleukin-4. Conclusions: We determined that SG-SP1 directly interacts with FcεRI and propose SG-SP1 as a therapeutic candidate for mast cell-mediated allergic inflammatory disorders via inhibition of FcεRI signaling.