Pore-size control of chitin nanofibrous composite membrane using metal-organic frameworks.

Herein, environmentally benign chitin nanofiber (ChNF) membranes were fabricated by regulating suspension behavior. The introduction of zeolitic imidazole frameworks (ZIF-8) into the composite membranes led to the domain formation of ChNF derived by coordinative interaction, resulting in pore size-tunable membranes. Based on the rheological, morphological, and structural characterizations, the driving force of pore-size control was studied in the aqueous suspension of ChNF and ZIF-8 according to the relative concentration. At critical concentration, the 30-ChNF membrane presents superior water permeance (40 LMH h-1) while maintaining a high rejection rate (>80% for all organic dyes). Moreover, the molecular size cut-off of the composite membranes for dyes can be controlled in the range of less than 1 nm to 2 nm. The experimental results provide a simple strategy for the preparation of pore tunable ChNF membranes using MOF with high mechanical strength, good durability, high flux, dye rejection, and antifouling ability.

Effects of curcumin on the bioavailability of dioxin-like pollutants in rats.

The effects of curcumin on the bioavailability of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) were investigated in Sprague-Dawley rats. Tetra- and penta-chlorinated PCDFs had the lowest bioavailability and hexa-chlorinated PCDD/Fs had the highest, while there was no obvious change in that of DL-PCBs. Curcumin markedly reduced the toxic equivalent (TEQ) of PCDD/Fs in rats, illustrating the potential to competitively inhibit absorption of PCDD/Fs by the epithelial cells of the small intestine due to the similar chemical structure (diphenyl) between curcumin and PCDD/Fs. Moreover, curcumin lowered the TEQ of DL-PCBs in the liver of male rats, but not female rats. The significant decrease in the bioavailability of PCDD/Fs and DL-PCBs demonstrates the potential detoxification mechanisms of curcumin.

Proteome Changes Reveal the Protective Roles of Exogenous Citric Acid in Alleviating Cu Toxicity in Brassica napus L.

Citric acid (CA), as an organic chelator, plays a vital role in alleviating copper (Cu) stress-mediated oxidative damage, wherein a number of molecular mechanisms alter in plants. However, it remains largely unknown how CA regulates differentially abundant proteins (DAPs) in response to Cu stress in Brassica napus L. In the present study, we aimed to investigate the proteome changes in the leaves of B. L. seedlings in response to CA-mediated alleviation of Cu stress. Exposure of 21-day-old seedlings to Cu (25 and 50 µM) and CA (1.0 mM) for 7 days exhibited a dramatic inhibition of overall growth and considerable increase in the enzymatic activities (POD, SOD, CAT). Using a label-free proteome approach, a total of 6345 proteins were identified in differentially treated leaves, from which 426 proteins were differentially expressed among the treatment groups. Gene ontology (GO) and KEGG pathways analysis revealed that most of the differential abundance proteins were found to be involved in energy and carbohydrate metabolism, photosynthesis, protein metabolism, stress and defense, metal detoxification, and cell wall reorganization. Our results suggest that the downregulation of chlorophyll biosynthetic proteins involved in photosynthesis were consistent with reduced chlorophyll content. The increased abundance of proteins involved in stress and defense indicates that these DAPs might provide significant insights into the adaptation of Brassica seedlings to Cu stress. The abundances of key proteins were further verified by monitoring the mRNA expression level of the respective transcripts. Taken together, these findings provide a potential molecular mechanism towards Cu stress tolerance and open a new route in accelerating the phytoextraction of Cu through exogenous application of CA in B. napus.

Hydrogen Sulfide Inhibits Formaldehyde-Induced Senescence in HT-22 Cells via Upregulation of Leptin Signaling.

It has been previously demonstrated that hydrogen sulfide (H2S) prevents formaldehyde (FA)-induced neurotoxicity. However, the exact mechanisms underlying this protection remain to be fully elucidated. Neuronal senescence is involved in FA-induced neurotoxicity. Leptin signaling has anti-aging function. The present work was to investigate the protection of H2S against FA-induced neuronal senescence and the mediatory role of leptin signaling. FA-exposed HT-22 cells were used as the vitro model of FA-induced neuronal senescence. The senescence-associated ß-galactosidase (SA-ß-Gal) positive cell was detected by ß-galactosidase staining. The expressions of P16INK4a, P21CIP1, leptin, and lepRb (leptin receptor) were measured by western blot. The proliferation, viability, and apoptosis of cells were evaluated by Trypan blue exclusion assay, Cell Counting Kit-8 (CCK-8) assay, and Flow cytometry analysis, respectively. We found that H2S suppressed FA-induced senescence, as evidenced by the decrease in SA-ß-Gal positive cells, the downregulations of P16INK4a and P21CIP1, as well as decrease in cell growth arrest, in HT-22 cells. Also, H2S upregulated the expressions of leptin and lepRb in FA-exposed HT-22 cells. Furthermore, leptin tA (a specific inhibitor of the leptin) abolished the protective effects of H2S on FA-induced senescence and neurotoxicity (as evidenced by the increase in cell viability and the decrease in cell apoptosis) in HT-22 cells. These results indicated that H2S prevents FA-induced neuronal senescence via upregulation of leptin signaling. Our findings offer a novel insight into the mechanisms underlying the protection of H2S against FA-induced neurotoxicity. FA upregulates the expressions of P16INK4a and P21CIP1 via inhibiting leptin signaling, which in turn induces senescence in HT-22 cells; H2S downregulates the expressions of P16INK4a and P21CIP1 via reversing FA-downregulated leptin signaling, which in turn prevents FA-induced senescence in HT-22 cells.

An overview of plant-based interventions to ameliorate arsenic toxicity.

The industrial and technological advancements in the world have also contributed to the rapid deterioration in the environment quality through introduction of obnoxious pollutants that threaten to destroy the subtle balance in the ecosystem. The environment contaminants cause severe adverse effects to humans, flora and fauna that are mostly irreversible. Chief among these toxicants is arsenic, a metalloid, which is considered among the most dangerous environmental toxins that leads to various diseases which affect the quality of life even when present in small quantities. Treatment of arsenic-mediated disorders still remains a challenge due to lack of effective options. Chelation therapy has been the most widely used method to detoxify arsenic. But this method is associated with deleterious effects leading various toxicities such as hepatotoxicity, neurotoxicity and other adverse effects. It has been discovered that indigenous drugs of plant origin display effective and progressive relief from arsenic-mediated toxicity without any side-effects. Further, these phytochemicals have also been found to aid the elimination of arsenic from the biological system and therefore can be more effective than conventional therapeutic agents in ameliorating arsenic-mediated toxicity. This review presents an overview of the toxic effects of arsenic and the therapeutic strategies that are available to mitigate the toxic effects with emphasis on chelation as well as protective and detoxifying activities of different phytochemicals and herbal drugs against arsenic. This information may serve as a primer in identifying novel prophylactic as well as therapeutic formulations against arsenic-induced toxicity.

Fermented camel milk by Lactococcus lactis subsp. cremoris attenuates erythrocytes oxidative stress-induced hematological and immunological damage in CCl4-intoxicated mice.

Fermented camel by Lactococcus lactis subsp. cremoris has been recently discovered to protect against the toxic effect of carbon tetrachloride (CCl4), but its beneficial effects in the presence of oxidative stress in the erythrocytes have not been established. In the present study, 28 mice were randomly divided into four groups: control group; CCl4 group: intoxicated by a single intraperitoneal injection (ip) of CCl4; group FCM-LLC + CCl4: pretreated with FCM-LLC daily during 14 days, and received a single dose of CCl4. FCM-LLC group received FCM-LLC alone. The occurrence of oxidative stress in erythrocytes was evidenced by an increase in lipid peroxidation, protein carbonyl, and changes in antioxidant enzyme activities and non-enzymatic antioxidant. The oxidative injury induced by CCl4 in the erythrocytes was confirmed by modifications in hematological parameters and decreases in protein, albumin, and globulin content in the serum of intoxicated mice. Therefore, CCl4 caused a significant decrease in immunotoxic indices, including immunoglobulin G (IgG), immunoglobulin M (Ig M), and immunoglobulin A (IgA) levels, and an increase of inflammatory markers such as C-reactive protein (CRP) level. Meanwhile, FCM-LLC effectively restored the parameters cited above to near-normal values. It can be suggested that fermented camel milk could regulate deviant physiological effects induced by CCl4 which is due to its powerful antioxidant and immunomodulatory and anti-inflammatory capacity.

Healing potential of Adiantum capillus-veneris L. plant extract on bisphenol A-induced hepatic toxicity in male albino rats.

Bisphenol A (BPA) is a widely used environmental pollutant in the production of plastics but causes hepatotoxicity in mammals. In the present study, we studied the BPA-induced oxidative stress in rats and ameliorative potential of Adiantum capillus-veneris L. plant. It was concluded that the BPA can reduce the body and liver weight, increase in biochemical levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total bilirubin, and disturb the normal hepatic physiology, histology, and metabolism. Additionally, liver histology shows hepatic necrosis, congestion, and vacuolization in exposed individuals. In contrast, simultaneous exposure of A. capillus-veneris and BPA showed declining trend in serum biomarker levels and normal histopathological structures. We conclude that the A. capillus-veneris plant is antioxidant in nature and can reduce the BPA-induced toxicity. These findings are very helpful to understand the BPA-induced hepatic toxicity and ameliorative potential of A. capillus-veneris plant and are of great importance in risk assessment of xenobiotics.

The effects of baicalein or baicalin on the colloidal stability of ZnO nanoparticles (NPs) and toxicity of NPs to Caco-2 cells.

Recent study suggested that the presence of phytochemicals in food could interact with nanoparticles (NPs) and consequently reduce the toxicity of NPs, which has been attributed to the antioxidant properties of phytochemicals. In this study, we investigated the interactions between ZnO NPs and two flavonoids baicalein (Ba) or baicalin (Bn) as well as the influence of the interactions on the toxicity of ZnO NPs to Caco-2 cells. The antioxidant properties of Ba and Bn were confirmed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays, with Ba being stronger. However, the presence of Ba or Bn did not significantly affect cytotoxicity, intracellular superoxide or release of inflammatory cytokines of Caco-2 cells after ZnO NP exposure. When Ba was present, the cellular viability of Caco-2 cells after exposure to ZnO NPs was slightly increased, associated with a modest decrease of intracellular Zn ions, but these effects were not statistically different. Ba was more effective than Bn at changing the hydrodynamic sizes, Zeta potential and UV-Vis spectra of ZnO NPs, which indicated that Ba might increase the colloidal stability of NPs. Taken together, the results of the present study indicated that the anti-oxidative phytochemical Ba might only modestly protected Caco-2 cells from the exposure to ZnO NPs associated with an insignificant reduction of the accumulation of intracellular Zn ions. These results also indicated that when assessing the combined effects of NPs and phytochemicals to cells lining gastrointestinal tract, it might be necessary to evaluate the changes of colloidal stability of NPs altered by phytochemicals.

Potential Role of L-Arginine and Vitamin E Against Bone Loss Induced by Nano-Zinc Oxide in Rats.

The purpose of this study was to illustrate the effects of zinc oxide nanoparticles (ZnO-NPs) administration on bone turnover and bone resorbing agents in rats and how L-arginine (L-arg) or vitamin E (vit E) co-administrations might affect them. Fasting rats were randomly divided into four groups (n = 10): G1-normal healthy animals; G2-ZnO-NPs-exposed rats (600 mg/kg-1/day-1); G3-ZnO-NPs-exposed rats co-administrated L-arg (200 mg/kg-1/day-1); G4-ZnO-NPs-exposed rats co-administrated vit E (200 mg/kg-1/day-1). The ingredients were orally administered daily. The body weight and food consumption of rats were recorded during the administration period and the experiment continued for three consecutive weeks. The results demonstrated that ZnO-NPs administration induced bone loss in rats as manifested by reduced activity of bone alkaline phosphatase (B-ALP) and increased level of C-terminal peptide type I collagen (CTx). The increase of inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by ZnO-NPs suggests that deleterious effects of ZnO-NPs on bone turnover were, in part, due to inflammation. Confirming to this suggestion, both L-arg and vit E reduced TNF-α and IL-6 levels and consequently decreased bone resorption as indicated by reduced serum CTx level. This study proved that ZnO-NPs can induce bone turnover, which may be reduced by L-arg or vit.E co-administration, partly by anti-inflammatory mechanism.

Luminescent lanthanide metal-organic frameworks for chemical sensing and toxic anion detection.

Prototype lanthanide metal-organic frameworks (LnMOFs), Ln(BTC) (Ln = Eu and Tb; BTC = benzene-1,3,5-tricarboxylate), have been considered as luminescent sensors for detecting toxic anions, while their neutral pore structures have limited the entrance and encapsulation of anions to produce highly anion-responsive photoluminescence (PL). To facilitate anions to enter the pore space of Ln(BTC), a one-pot synthesis method was proposed in which BTC was partially replaced with its structural analogue L·BF4 (H3L·BF4 = 2,4,6-tricarboxy-1-methylpyridinium tetrafluoroborate) which consists of an anion affinity site of cationic methylpyridinium. Compared to the original Ln(BTC), the co-doped cationic framework Eu0.05Tb0.95-BTC0.9L0.1 is highly sensitive for detecting different toxic anions by tuning the energy absorption of organic chromophores, the energy transfer efficiency to Ln3+ ions and the energy allocation between different Ln3+ ions in the PL spectra. We demonstrated that the Eu0.05Tb0.95-BTC0.9L0.1 PL sensor has the capability of decoding various toxic anions with a clearly differentiable and unique emission intensity ratio of 5D4 → 7F5 (Tb3+, 545 nm) to 5D0 → 7F2 (Eu3+, 618 nm) transitions (ITb/IEu). Compared to Ln(BTC), the co-doped Eu0.05Tb0.95-BTC0.9L0.1 presents self-calibrating, high distinguishable and stable PL signals for detecting toxic anions.

Effects of Nano-zinc on Biochemical Parameters in Cadmium-Exposed Rats.

Cadmium (Cd) is a toxic environmental and occupational pollutant with reported toxic effects on the kidneys, liver, lungs, bones, and the immunity system. Based on its physicochemical similarity to cadmium, zinc (Zn) shows protective effects against cadmium toxicity and cadmium accumulation in the body. Nano-zinc and nano-zinc oxide (ZnO), recently used in foods and pharmaceutical products, can release a great amount of Zn2+ in their environment. This research was carried out to investigate the more potent properties of the metal zinc among sub-acute cadmium intoxicated rats. Seventy-five male Wistar rats were caged in 15 groups. Cadmium chloride (CdCl2) was used in drinking water to induce cadmium toxicity. Different sizes (15, 20, and 30 nm) and doses of nano-zinc particles (3, 10, 100 mg/kg body weight [bw]) were administered solely and simultaneously with CdCl2 (2-5 mg/kg bw) for 28 days. The experimental animals were decapitated, and the biochemical biomarkers (enzymatic and non-enzymatic) were determined in their serum after oral exposure to nano-zinc and cadmium. Statistical analysis was carried out with a one-way ANOVA and t test. P < 0.05 was considered as statistically significant. The haematocrit (HCT) significantly increased and blood coagulation time significantly reduced in the nano-zinc-treated rats. AST, ALT, triglyceride, total cholesterol, LDL, and free fatty acids increased significantly in the cadmium- and nano-zinc-treated rats compared with the controls. However, albumin, total protein, and HDLc significantly decreased in the cadmium- and nano-zinc-treated rats compared with the controls (P < 0.05). It seems that in the oral administration of nano-zinc, the smaller sizes with low doses and the larger sizes with high doses are more toxic than metallic zinc. In a few cases, an inverse dose-dependent relationship was seen as well. This research showed that in spite of larger sizes of zinc, smaller sizes of nano-zinc particles are not suitable for protection against cadmium intoxication.

Environmental biomonitoring of essential and toxic elements in human scalp hair using accelerated microwave-assisted sample digestion and inductively coupled plasma optical emission spectroscopy.

Human scalp hair samples were collected and used to assess exposure to toxic elements and essential elements in the state of North Carolina, USA using accelerated microwave assisted acid digestion and inductively coupled plasma optical emission spectroscopy (ICP-OES). The figures-of-merit of the ICP-OES were appropriate for elemental analysis in scalp hair with detection limits as low as 0.0001 mg/L for Cd, good linearity (R2 > 0.9978), and percent recoveries that ranged from 96 to 106% for laboratory-fortified-blanks and 88-112% for sample spike recovery study. The concentrations of essential elements in scalp hair were larger than those of toxic elements, with Ca having the highest average concentration (3080 µg/g, s = 14,500, n = 194). Some of the maximum concentrations observed for As (65 µg/g), Ni (331 µg/g), Cd (2.96 µg/g), and Cr (84.6 µg/g) in individual samples were concerning, however. Samples were statistically analyzed to determine the influence of race, gender, smoking habits, or age on the elemental concentrations in scalp hair. Higher concentrations of essential elements were observed in the scalp hair of Caucasians, females, and non-smokers, and the differences were often significant at a 90% confidence level. Several pairs of essential elements, for example Ca-K, Ca-Mg, and Ca-Zn, were strongly correlated in Caucasian hair but uncorrelated in African-American hair. Similarly, essential elements were strongly correlated in female hair but weakly correlated in male hair. Toxic element pairs (As-Cd, As-Se, Pb-As, and Se-Cd) were strongly correlated in the hair of smokers but uncorrelated in that of non-smokers, suggesting that cigarette smoke is a common source of toxic elements in humans.

Potential roles for calcium-sensing receptor (CaSR) and transient receptor potential ankyrin-1 (TRPA1) in murine anorectic response to deoxynivalenol (vomitoxin).

Food contamination by the trichothecene mycotoxin deoxynivalenol (DON, vomitoxin) has the potential to adversely affect animal and human health by suppressing food intake and impairing growth. In mice, the DON-induced anorectic response results from aberrant satiety hormone secretion by enteroendocrine cells (EECs) of the gastrointestinal tract. Recent in vitro studies in the murine STC-1 EEC model have linked DON-induced satiety hormone secretion to activation of calcium-sensing receptor (CaSR), a G-coupled protein receptor, and transient receptor potential ankyrin-1 (TRPA1), a TRP channel. However, it is unknown whether similar mechanisms mediate DON's anorectic effects in vivo. Here, we tested the hypothesis that DON-induced food refusal and satiety hormone release in the mouse are linked to activation of CaSR and TRPA1. Oral treatment with selective agonists for CaSR (R-568) or TRPA1 (allyl isothiocyanate (AITC)) suppressed food intake in mice, and the agonist's effects were suppressed by pretreatment with corresponding antagonists NPS-2143 or ruthenium red (RR), respectively. Importantly, NPS-2143 or RR inhibited both DON-induced food refusal and plasma elevations of the satiety hormones cholecystokinin (CCK) and peptide YY3-36 (PYY3-36); cotreatment with both antagonists additively suppressed both anorectic and hormone responses to DON. Taken together, these in vivo data along with prior in vitro findings support the contention that activation of CaSR and TRPA1 contributes to DON-induced food refusal by mediating satiety hormone exocytosis from EEC.

Protective effect of citicoline against aluminum-induced cognitive impairments in rats.

The potential protective effect of citicoline on aluminum chloride-induced cognitive deficits was investigated in rats. In a Morris water maze, administration of aluminum chloride to rats for 90 days resulted in increased escape latency to reach the platform and decreased swimming speed in acquisition trials. Similarly, in probe trials, the time required to reach the hidden platform was increased and the time spent in the target quadrant was reduced. Also, administration of aluminum chloride to rats for 90 days increased the reference and working memory errors and time required to end the task in the radial arm maze. In addition, this treatment decreased the step-through latency in the passive avoidance test. Concurrently, treatment of rats with aluminum chloride for 90 days increased hippocampal glutamate, malondialdehyde, and nitrite levels and decreased intracellular reduced glutathione level. In the citicoline-treated group, aluminum chloride-induced learning and memory impairments as assessed by the Morris water maze, radial arm maze, and passive avoidance tests were inhibited. At the same time, treatment of rats with citicoline prevented the biochemical alterations induced by aluminum chloride in the hippocampus. It can be concluded that elevation of hippocampal glutamate level with consequent oxidative stress and nitric oxide (NO) overproduction may play an important role in aluminum-induced cognitive impairments. Also, our results suggest, for the first time, that citicoline can protect against the development of these cognitive deficits through inhibition of aluminum-induced elevation of glutamate level, oxidative stress, and NO overproduction in the hippocampus.

Pleiotropic roles of Ca+2/calmodulin-dependent pathways in regulating cadmium-induced toxicity in human osteoblast-like cell lines.

The heavy metal cadmium is a widespread environmental contaminant that has gained public attention due to the global increase in cadmium-containing electronic waste. Human exposure to cadmium is linked to the pathogenesis of osteoporosis. We previously reported cadmium induces apoptosis and decreases alkaline phosphatase mRNA expression via extracellular signal-regulated protein kinase (ERK) activation in Saos-2 bone-forming osteoblasts. This study examines the mechanisms of cadmium-induced osteotoxicity by investigating roles of Ca+2/calmodulin-dependent protein kinase (CAMK) pathways. Saos-2 or MG-63 cells were treated for 24 or 48h with 5µM CdCl2 alone or in combination with calmodulin-dependent phosphodiesterase (PDE) inhibitor CGS-9343ß; calmodulin-dependent kinase kinase (CAMKK) inhibitor STO-609; or calmodulin-dependent kinase II (CAMKII) inhibitor KN-93. CGS-9343ß protected against cadmium-induced toxicity and attenuated ERK activation; STO-609 enhanced toxicity and exacerbated ERK activation, whereas KN-93 had no detectable effect on cadmium-induced toxicity. Furthermore, CGS-9343ß co-treatment attenuated cadmium-induced apoptosis; but CGS-9343ß did not recover cadmium-induced decrease in ALP activity. The major findings suggest the calmodulin-dependent PDE pathway facilitates cadmium-induced ERK activation leading to apoptosis, whereas the CAMKK pathway plays a protective role against cadmium-induced osteotoxicity via ERK signaling. This research distinguishes itself by identifying pleiotropic roles for CAMK pathways in mediating cadmium's toxicity in osteoblasts.

Arginine decarboxylase: A novel biological target of mercury compounds identified in PC12 cells.

Mercury compounds are well-known toxic environmental pollutants and potently induce severe neurotoxicological effects in human and experimental animals. Previous studies showed that one of the mechanisms of mercury compounds neurotoxicity arose from the over-activation of the N-methyl d-aspartate (NMDA)-type glutamate receptor induced by increased glutamate release. In this work, we aimed to investigate the molecular mechanisms of Hg compounds neurotoxicities by identifying their biological targets in cells. Firstly, the inhibitory effects of four Hg compounds, including three organic (methyl-, ethyl- and phenyl-mercury) and one inorganic (Hg2+) Hg compounds, on the activity of arginine decarboxylase (ADC), a key enzyme in the central agmatinergic system, were evaluated. They were found to inhibit the ADC activity significantly with methylmercury (MeHg) being the strongest (IC50=7.96nM). Furthermore, they showed remarkable inhibitory effects on ADC activity in PC12 cells (MeHg>EtHg>PhHg>HgCl2), and led to a marked loss in the level of agmatine, an endogenous neuromodulatory and neuroprotective agent that selectively blocks the activation of NMDA receptors. MeHg was detected in the immunoprecipitated ADC from the cells, providing unequivocal evidence for the direct binding of MeHg with ADC in the cell. Molecular dynamics simulation revealed that Hg compounds could form the coordination bond not only with cofactor PLP of ADC, but also with substrate arginine. Our finding indicated that MeHg could attenuate the neuroprotective effects of agmatine by the inhibition of ADC, a new cellular target of MeHg, which might be implicated in molecular mechanism of MeHg neurotoxicity.

Resveratrol ameliorates benzo(a)pyrene-induced testicular dysfunction and apoptosis: involvement of p38 MAPK/ATF2/iNOS signaling.

Benzo(a)pyrene [B(a)P] is an environmental toxicant that alters the steroidogenic profile of testis and induces testicular dysfunction. In the present study, we have investigated the molecular signaling of B(a)P and the ameliorative potential of the natural aryl hydrocarbon receptor (AhR) antagonist and antioxidant, resveratrol, on B(a)P-induced male reproductive toxicity. Studies showed that B(a)P treatment resulted in p38 MAPK activation and increased inducible nitric oxide synthase (iNOS) production along with testicular apoptosis and steroidogenic dysfunction. Resveratrol cotreatment maintained testicular redox potential, increased serum testosterone level and enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3ßHSD, 17ßHSD) and prevented subsequent onset of apoptosis. Resveratrol cotreatment resulted inhibition of testicular cytochrome P4501A1 (CYP1A1) expression, which is the major B(a)P metabolizing agent for BPDE-DNA adduct formation. Resveratrol also significantly decreased the B(a)P-induced AhR protein level, its nuclear translocation and subsequent promoter activation, thereby decreased the expression of CYP1A1. Resveratrol also down-regulated B(a)P-induced testicular iNOS production through suppressing the activation of p38 MAPK and ATF2, thus improved the oxidative status of the testis and prevented apoptosis. Our findings cumulatively suggest that resveratrol inhibits conversion of B(a)P into BPDE by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Toxicological effects of fumonisin B1 alone and in combination with other fusariotoxins on bovine granulosa cells.

There is now overwhelming evidence of global contamination of commodities with Fusarium mycotoxins. Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in corn in combination with deoxynivalenol (DON), α-zearalenol (α-ZEA) and ß-zearalenol (ß-ZEA). The aim of this study was to determine if FB1, alone and combined with DON or α-ZEA or ß-ZEA, can affect cell proliferation and steroid production of bovine granulosa cells (GC). A species-specific model with bovine granulosa cells (GC) was used to study the potential endocrine disruptor effects of FB1 alone and in co-exposure. In the presence of ß-ZEA (30 ng/mL), FB1 at 30 ng/mL showed a stimulatory effect on GC numbers. Insulin-like growth factor-1 (IGF1)-stimulated cell proliferation was decreased after exposure to ß-ZEA alone at 5.0 µg/mL and FB1 with α-ZEA and ß-ZEA at the same concentration. Regarding steroid production, FB1 at 30 ng/mL and 100 ng/mL amplified the inhibitory effect of ß-ZEA (30 ng/mL) on estradiol (E2) production, while FB1 alone increased (P < 0.05) IGF1-induced E2 production. α-ZEA alone decreased (P < 0.05) E2 production, whereas ß-ZEA alone and in combination with FB1 decreased (P < 0.05) E2 production. These studies indicate for the first time that the Fusarium mycotoxin FB1 along with other mycotoxins can affect GC proliferation and steroid production, which ultimately could influence reproductive function in cattle.

Polyamine and nitric oxide crosstalk: Antagonistic effects on cadmium toxicity in mung bean plants through upregulating the metal detoxification, antioxidant defense and methylglyoxal detoxification systems.

Cadmium (Cd) contamination is a serious agricultural and environmental hazard. The study investigates cross-protection roles of putrescine (Put, 0.2 mM) and nitric oxide (sodium nitroprusside; SNP, 1 mM) in conferring Cd (CdCl2, 1.5 mM) tolerance in mung bean (Vigna radiata L. cv. BARI Mung-2) seedlings. Cadmium stress increased root and shoot Cd content, reduced growth, destroyed chlorophyll (chl), modulated proline (Pro) and reduced leaf relative water content (RWC), increased oxidative damage [lipid peroxidation, H2O2 content, O2(∙-) generation rate, lipoxygenase (LOX) activity], methylglyoxal (MG) toxicity. Put and/or SNP reduced Cd uptake, increasd phytochelatin (PC) content, reduced oxidative damage enhancing non-enzymatic antioxidants (AsA and GSH) and activities of enzymes [superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione S-transferase (GST), and glutathione peroxidase (GPX)]. Exogenous Put and/or SNP modulated endogenous polyamines, PAs (putrescine, Put; spermidine, Spd; spermine, Spm), and NO; improved glyoxalase system in detoxifying MG and improved physiology and growth where combined application showed better effects which designates possible crosstalk between NO and PAs to confer Cd-toxicity tolerance.

Melatonin controlled apoptosis and protected the testes and sperm quality against bisphenol A-induced oxidative toxicity.

Epidemiological reports have indicated a correlation between the increasing bisphenol A (BPA) levels in the environment and the incidence of male infertility. In this study, the protective effects of melatonin on BPA-induced oxidative stress and apoptosis were investigated in the rat testes and epididymal sperm. Melatonin (10 mg/kg body weight (bw)) was injected concurrently with BPA (50 mg/kg bw) for 3 and 6 weeks. The administration of BPA significantly increased oxidative stress in the testes and epididymal sperm. This was associated with a decrease in the serum testosterone level as well as sperm quality, chromatin condensation/de-condensation level, and the percentage of haploid germ cells in the semen. BPA administration caused a significant increase in apoptosis accompanied by a decrease in the expression of the antiapoptotic proteins Bcl-2 in the testes and epididymal sperm. The concurrent administration of melatonin decreased oxidative stress by modulating the levels of glutathione, superoxide dismutase, and catalase as well as the malondialdehyde and hydrogen peroxide concentrations in the testes and sperm. Melatonin sustained Bcl-2 expression and controlled apoptosis. Furthermore, melatonin maintained the testosterone levels, ameliorated histopathological changes, increased the percentages of seminal haploid germ cells, and protected sperm chromatin condensation process, indicating appropriate spermatogenesis with production of functional sperm. In conclusion, melatonin protected against BPA-induced apoptosis by controlling Bcl-2 expression and ameliorating oxidative stress in the testes and sperm. Thus, melatonin is a promising pharmacological agent for preventing the potential reproductive toxicity of BPA following occupational or environmental exposures.