Aflatoxin B1-induced redox imbalance in the hippocampus and cerebral cortex of male Wistar rats is accompanied by altered cholinergic, indoleaminergic, and purinergic pathways: Abatement by dietary rutin.

The neurotoxic impact of dietary exposure to aflatoxin B1 (AFB1) is well documented in experimental studies. Rutin is a phytochemical with prominent anti-inflammatory and antioxidant activities. There is an information gap on the influence of rutin on AFB1-induced neurotoxicity. This study investigated the influence of rutin on neurobehavioral and biochemical abnormalities in male Wistar rats (six weeks old) orally treated with AFB1 (0.75, and 1.5 mg/kg body weight) or co-administered with rutin (50 mg/kg) for 30 uninterrupted days. Results indicate that AFB1-induced depression-like behavior by Tail Suspension Test (TST) and cognitive impairment by Y-maze was abated following rutin co-administration. Abatement of AFB1-induced decreases in acetylcholinesterase (AChE) activity, and increased antioxidant status, by rutin was accompanied by a marked reduction in oxidative stress markers and increased hydrolysis of the purinergic molecules in the cerebral cortex and hippocampus of rats. Additionally, rutin co-treatment abrogated AFB1-mediated elevation of interleukin-6 (IL-6), nitric oxide (NO) levels, and activity of myeloperoxidase (MPO). Correspondingly, rutin co-treatment lowered the activity and immunocontent of immunosuppressive indoleamine 2, 3-dioxygenase (IDO). Further, rutin co-treatment prevented histological injuries in the cerebral cortex and hippocampus. In conclusion, abatement of AFB1-induced neurobehavioral abnormalities by rutin involves the mechanisms of anti-inflammatory, antioxidant, and regulation of cholinergic, purinergic, and indoleaminergic pathways in rats.

Zinc Ameliorates Cadmium-Induced Immunotoxicity by Modulating Splenic Immunosuppressive Indoleamine 2,3-Dioxygenase Activity, Hematological Indices, and CD4+ T Cells via Inhibition of Cadmium Uptake in Male Wistar Rats.

Cadmium (Cd)-induced immunotoxicity has become a matter of public health concern owing to its prevalence in the environment consequently, great potential for human exposure. Zinc (Zn) has been known to possess antioxidant, anti-inflammatory, and immune-boosting properties. However, the ameliorating influence of Zn against Cd-induced immunotoxicity connecting the IDO pathway is lacking. Adult male Wistar rats were exposed to normal drinking water with no metal contaminants (group 1), group 2 received drinking water containing 200 µg/L of Cd, group 3 received drinking water containing 200 µg/L of Zn, and group 4 received Cd and Zn as above in drinking water for 42 days. Cd exposure alone significantly triggered the splenic oxidative-inflammatory stress, increased activities of immunosuppressive tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenases (IDO) activities/protein expression, and decreased CD4+ T cell count, and a corresponding increase in the serum kynurenine concentration, as well as alterations in the hematological parameters and histologic structure when compared with the control (p < 0.05). Zn alone did not have any effect relative to the control group while co-exposure significantly (p < 0.05) assuaged the Cd-induced alterations in the studied parameters relative to the control. Cd-induced modifications in IDO 1 protein expression, IDO/TDO activities, oxidative-inflammatory stress, hematological parameters/CD4+ T cell, and histological structure in the spleen of rats within the time course of the investigation were prevented by Zn co-exposure via inhibition of Cd uptake.

The antioxidant/anti-inflammatory protective effects of rutin against ethanol-induced testicular perturbation in rats: Involvement of the immunosuppressive indoleamine 2,3-dioxygenase.

This study investigated the influence of rutin against EtOH-induced testicular impairment in rats and the involvement of the indole-aminergic pathway. Four groups of eight rats each were orally exposed to drinking water (Group 1), EtOH (5 g/kg bwt, Group 2), R (5 g/kg bwt, Group 3), and EtOH + R (5 g/kg bwt + 50 mg/kg bwt, Group 4) via gavage for 15 days. Results showed that exposure to EtOH significantly (p < 0.0001) reduced the testicular antioxidant system and increased lipid peroxidation (LPO) relative to control. We observed a significant (p < 0.0001) increase in the inflammatory biomarkers, with attendant disruption in the testicular histological structure and concomitant elevation in the activities of indoleamine 2,3-dioxygenase (IDO), in comparison with control and no noticeable effects in tryptophan 2,3-dioxygenase (TDO) activity across the groups. Rutin-only exposed group did not show any alteration in the measured parameters when compared with the control. Rutin co-exposure augmented the antioxidant system, prevented histological damage, reduced LPO and inflammation, and thus, lowered EtOH-mediated increase in IDO activity, compared with control. Overall, these findings reveal the involvement of the indole-aminergic pathway in rutin's protective influence against EtOH-induced testicular impairment in rats.

Rutin co-treatment prevented cognitive impairment/depression-like behavior and decreased IDO activation following 35 days of ethanol administration in male Wistar rats.

Alcohol (ethanol) is among the most popularly consumed beverages globally. Ethanol was earlier demonstrated to elicit cognitive impairment and depressive-like effects in both human and animal studies. Rutin (R) is known for its antioxidant, anti-inflammatory, immunomodulatory, and anti-depressive properties, among others. Herein, we investigate the impact of rutin on ethanol-induced cognitive impairment and depressive-like effects in rats and the involvement of the indoleaminergic pathway. Three groups of eight rats each were orally exposed to drinking water (group 1), ethanol (5 g/kg body weight)-group 2 (via oral gavage), and ethanol + R (5 g/kg body weight + 50 mg/kg body weight)-group 3 (via oral gavage) for 35 days. Results showed that exposure to ethanol significantly (p < 0.0001) reduced spontaneous alternation in the Y-maze and increased immobility time in the tail suspension test (TST), which indicates cognitive impairment and depressive-like behavior in rats. We observed increased IDO activity/expression, and inflammatory responses, with attendant disruption in antioxidant systems and concomitant elevation in malondialdehyde (MDA) levels in the cerebral cortex and hippocampus. Following rutin co-exposure, an ethanol-mediated increase in indoleamine 2,3-dioxygenase [IDO] activity/expression and decrease in antioxidant enzymes, in addition to an increase in markers of inflammatory response and MDA production, was significantly (p < 0.0001) prevented compared with controls. Additionally, altered behavioral indices were prevented by rutin co-exposure. Taken together, these findings reveal the involvement of the indoleaminergic pathway in rutin preventive influence against ethanol-induced cognitive impairment and depressive-like behavior in rats.

Cyclophosphamide-induced testicular oxidative-inflammatory injury is accompanied by altered immunosuppressive indoleamine 2, 3-dioxygenase in Wister rats: Influence of dietary quercetin.

This study evaluated the role of quercetin against cyclophosphamide-induced distortion of rat testicular function. Adult rats were administered cyclophosphamide (100 mg/kg), quercetin (50 mg/kg) and in combination for seven days. Cyclophosphamide caused a significant increase in the activities of indoleamine 2, 3-dioxygenases (IDO), tryptophan 2, 3-dioxygenase (TDO), myeloperoxidase (MPO), and elevated the concentrations of interleukin 6 (IL-6) and interferon-γ (IFN-γ). Cyclophosphamide increased testis malondialdehyde (MDA) concentrations but depleted superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione (GSH). However, quercetin co-administration significantly (p < 0.05) prevented the increased values of IDO, TDO, MPO, IL-6, IFN-γ, MDA, SOD, CAT, GSH-Px and GSH compared with control rats. Also, quercetin co-treatment significantly increased serum testosterone, follicle-stimulating hormone (FSH), prolactin, luteinizing hormone (LH), activities of testicular 3ß-hydroxysteroid dehydrogenase (3 ß-HSD), 17ß-hydroxysteroid dehydrogenase (17 ß-HSD) as well as sperm count, motility and viability but reduced abnormal sperm morphology. Quercetin exposure alone did not alter any of the parameters evaluated relative to control. Thus, quercetin protected the testes against cyclophosphamide-induced alterations in immunosuppressive IDO/TDO activities elicited by oxidative-inflammatory mediators.

Cyclophosphamide instigated hepatic-renal oxidative/inflammatory stress aggravates immunosuppressive indoleamine 2,3-dioxygenase in male rats: Abatement by quercetin.

The hepatic-renal toxicity associated with cyclophosphamide (CYP) treatment in both animals and humans have been reported. Quercetin, a dietary flavonoid, is known to elicit beneficial health effects. However, the influence of quercetin on the hepatic-renal toxicity associated with CYP-instigated indoleamine 2,3-dioxygenase is unavailable in the literature. The current study evaluated the effects of quercetin on the dysfunctional hepatic-renal status triggered by CYP exposure in rats. Experimental animals were exposed to CYP (100 mg/kg) or co-treated with quercetin (50 mg/kg) every other day for 7 days. Results revealed that quercetin treatment significantly assuaged CYP-mediated oxidative-inflammatory response, as well as augmenting serum levels of thyroid hormones. Additionally, quercetin attenuated CYP-induced reduction in antioxidant enzyme activities and enhanced hepatic-renal function markers, namely aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and levels of urea and creatinine. Quercetin efficiently mitigated CYP-mediated increase in myeloperoxidase (MPO) activity, levels of nitric oxide and interleukin-6 (IL-6) in liver and kidney of rats. CYP-induced increase in the activities of immunosuppressive indoleamine 2, 3-dioxygenase (IDO) and tryptophan 2, 3-dioxygenase (TDO) in the tissues was abated in quercetin co-treated rats. In conclusion, Quercetin ameliorated deficits in the hepatic-renal function in CYP-exposed rats by lowering the activities/expression of immunosuppressive IDO and TDO via diminution of oxidative-inflammatory stress.

Salinomycin promotes T-cell proliferation by inhibiting the expression and enzymatic activity of immunosuppressive indoleamine-2,3-dioxygenase in human breast cancer cells.

Indoleamine 2,3 dioxygenase (IDO) is upregulated in many tumor types, including breast cancer, and plays a reputable role in promoting tumor immune tolerance. The importance of the immunosuppressive mechanism of IDO by suppressing T-cell function has garnered profound interest in the development of clinical IDO inhibitors. Herein, we established a screening method with cervical HeLa cells to induce IDO expression using interferon-γ (IFN-γ). After screening our chemical library, we found that salinomycin potently inhibited IFN-γ-stimulated kynurenine synthesis with IC50 values of 3.36-4.66 µM in both human cervical and breast cancer cells. Salinomycin lowered the IDO1 and IDO2 expression with no impact on the expression of tryptophan-2,3-dioxygenase. Interestingly, salinomycin potently repressed the IDO1 enzymatic activity by directly targeting the proteins in cells. Molecular docking revealed an alignment that favors nucleophilic attack of salinomycin in the catalytic domain of IDO1. Activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway by IFN-γ was significantly suppressed by salinomycin, via inhibiting the Jak1, Jak2, and STAT1/3 phosphorylation. Moreover, it inhibited IFN-γ-induced activation of the nuclear factor (NF)-κB pathway by inhibiting IκB degradation and NF-κB phosphorylation without affecting BIN1 expression. Furthermore, salinomycin significantly restored the proliferation of T cells co-cultured with IFN-γ-treated breast cancer cells and potentiated antitumor activity of cisplatin in vivo. These findings suggest that salinomycin suppresses kynurenine synthesis by inhibiting the catalytic activity of IDO1 and its expression by inhibiting the JAK/STAT and NF-κB pathways. Salinomycin warrants further investigation as a novel dual-functional IDO inhibitor for cancer immunotherapy.

Loranthus micranthus nanoparticles abates streptozotocin-instigated testicular dysfunction in Wistar rats: Involvement of glucose metabolism enzymes, oxido-inflammatory stress, steroidogenic enzymes/protein and Nrf2 pathway.

Loranthus micranthus (African mistletoe)-Loranthaceae family, is used in Nigerian traditional medicine for treating male infertility and lowering diabetic blood sugar levels. We investigated possible mechanism(s) involved in mitigation of L. micranthus leaves nanoparticles (LMLNPs) on streptozotocin (STZ)-induced testicular alterations. Type two diabetes mellitus (T2DM) was induced in male rats following 2 weeks feeding with fructose and single intraperitoneal injection of STZ. Control (nondiabetic) and (diabetic) rats received buffer only. Diabetic rats were treated with metformin or LMLNPs (two different doses) for 28 days. Hormonal profile, oxido-inflammatory stress parameters, glucose metabolism and steroidogenic enzymes/regulatory protein (StAR) and Nuclear factor erythroid 2-related factor 2 (Nrf2) protein in testes and sperm parameters were evaluated. Metformin and LMLNPs treatment significantly reduced blood glucose level in diabetic rats. Furthermore, LMLNPs enhanced glucose metabolism and testicular steroidogenic enzymes/protein, increased reproductive hormone levels and sperm functional parameters in diabetic rats. Additionally, LMLNPs suppressed testicular oxido-inflammatory stress biomarkers and inhibited lipid peroxidation in diabetic rats while augmenting Nrf2 pathway. Conclusively, LMLNPs potently reversed adverse effects of T2DM testicular dysfunction of rats. Use of LMLNPs in abating diabetic consequences proves an acceptable alternative to traditional crude extract preparations, as a result of better packaging and preservation.

Antimicrobial and Wound Healing Properties of Polyacrylonitrile-Moringa Extract Nanofibers.

A simple and cost-effective material composed of polyacrylonitrile nanofibers containing different concentrations of moringa (MR) leaf extracts was fabricated for antimicrobial properties and wound dressing. The fabricated materials were characterized by scanning electron microscopy, thermal gravimetric analysis, and Fourier transmission infrared spectroscopy. The antibacterial sensitivity of the developed polyacrylonitrile-moringa extract nanofibers was evaluated against Staphylococcus aureus and Escherichia coli by the agar diffusion method. A pronounced antibacterial activity was observed with the increase in the incorporated moringa leaf extract concentration within the polyacrylonitrile-moringa extract nanofibers against the bacterial strains. The best antibacterial sensitivity was observed for nanofibers containing 0.5 g of moringa leaf extract which had an inhibitory zone of 15 mm for E. coli and 12 mm for S. aureus. Furthermore, the cost-effective and biodegradable nanofibrous polyacrylonitrile-moringa extract nanofiber was also used to conduct further studies regarding wound dressing. The result reveals that the increase in the concentrations of moringa leaf extract influenced the healing properties of the material. For days 1, 4, and 7 of the wound dressing experiment, the % wound closure of the rat was the highest for the nanofiber containing 0.5 g of moringa leaf extract (35, 87, and 95%, respectively) compared to the positive control medical gauze (29, 75, and 93%, respectively).

Natural Nanoparticles: A Particular Matter Inspired by Nature.

During the last couple of decades, the rapidly advancing field of nanotechnology has produced a wide palette of nanomaterials, most of which are considered as "synthetic" and, among the wider public, are often met with a certain suspicion. Despite the technological sophistication behind many of these materials, "nano" does not always equate with "artificial". Indeed, nature itself is an excellent nanotechnologist. It provides us with a range of fine particles, from inorganic ash, soot, sulfur and mineral particles found in the air or in wells, to sulfur and selenium nanoparticles produced by many bacteria and yeasts. These nanomaterials are entirely natural, and, not surprisingly, there is a growing interest in the development of natural nanoproducts, for instance in the emerging fields of phyto- and phyco-nanotechnology. This review will highlight some of the most recent-and sometimes unexpected-advances in this exciting and diverse field of research and development. Naturally occurring nanomaterials, artificially produced nanomaterials of natural products as well as naturally occurring or produced nanomaterials of natural products all show their own, particular chemical and physical properties, biological activities and promise for applications, especially in the fields of medicine, nutrition, cosmetics and agriculture. In the future, such natural nanoparticles will not only stimulate research and add a greener outlook to a traditionally high-tech field, they will also provide solutions-pardon-suspensions for a range of problems. Here, we may anticipate specific biogenic factories, valuable new materials based on waste, the effective removal of contaminants as part of nano-bioremediation, and the conversion of poorly soluble substances and materials to biologically available forms for practical uses.

Transient effect of single dose exposure of Nigerian Bonny-light crude oil on testicular steroidogenesis in Wistar rats is accompanied by oxidative stress.

The folkloric use of Nigerian Bonny-light crude oil (BLCO) in Niger Delta area of Nigeria is a common practice. There is increasing experimental evidence portending the adverse effects of BLCO an environmental toxicant on testicular function. We investigated the effects of single dose of BLCO (800 mg/kg body weight) on the activities of steroidogenic and antioxidant enzymes such as serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone, 3 ß-hydroxy-steroid dehydrogenase (3 ß-HSD), 17 ß-hydroxy-steroid dehydrogenase (17 ß-HSD), superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione peroxidase (GSH-Px), levels of lipid peroxidation (LPO), glutathione reduced (GSH) and steroidogenic acute regulatory (StAR) protein, in testes of rats. There was a sequential reduction in the concentration of steroid hormones and activities of steroidogenic enzymes with a concomitant decrease in levels of StAR protein, followed by a parallel increase in antioxidant enzyme activities and levels of LPO. These findings revealed inhibitory effects of BLCO on testicular steroidogenesis and the possible role of oxidative stress in testicular dysfunction observed in this study.