Plants as effective bioindicators for heavy metal pollution monitoring.

This study investigated the bioindicator potential of Amaranthus retroflexus L., Plantago lanceolata L., Rumex acetosa L., and Trifolium pratense L. including the use of Lolium multiflorum L. as a reference species, for heavy metal pollution monitoring, in particular Zinc (Zn), Cadmium (Cd), Nickel (Ni), and Lead (Pb). Controlled heavy metal contamination was applied through irrigation with metal nitrate solutions two levels of contamination (low and high). The study also focused on analyzing heavy metals concentration in plant tissues and related physiological responses. Distinct physiological responses to heavy metal stress were observed among the investigated species, highlighting unique variations in their reactions. Hydrogen peroxide, malondialdehyde content, and enzymatic activities emerged as reliable indicators of plant stress induced by heavy metal solutions. P. lanceolata displayed elevated Zn concentrations in both roots and leaves (3271 ± 337 and 4956 ± 82 mg kg-1). For Pb, L. multiflorum and P. lanceolata showed highest root concentrations (2964 ± 937 and 1605 ± 289 mg kg-1), while R. acetosa had higher leaf concentration (1957 ± 147 mg kg-1). For Ni, L. multiflorum had the highest root concentration (1148 ± 93 mg kg-1), and P. lanceolata exhibited the highest leaf concentration (2492 ± 28 mg kg-1). P. lanceolata consistently demonstrated the highest Cd concentrations in both roots (126 ± 21 mg kg-1) and leaves (163 ± 12 mg kg-1). These results provide valuable insights for selecting effective bioindicator species to establish control strategies for heavy metal pollution.

Nutraceuticals and peripheral glial cells: a possible link?

A nutraceutical is a food-derived molecule that provides medical or health benefits beyond its basic nutritional role, including the prevention and treatment of disease and its symptoms. In the peripheral nervous system, satellite glial cells are found in close relationship with neurons, mainly in peripheral sensory ganglia, but, compared with other glial cells, the relationship between these cells and nutraceuticals has received little attention. After describing satellite glial cells and their role and changes in physiology and pathology, we review the studies on the effects of nutraceuticals as modulators of their functions. Maybe due to the difficulties in selectively labeling these cells, only a few studies, performed mainly in rodent models, have analyzed nutraceutical effects, showing that N-acetylcysteine, curcumin, quercetin, osthole and resveratrol may palliate neuropathic pain through satellite glial cells-dependent pathways, namely antioxidant mechanisms and/or interference with purinergic signaling. Neither other conditions in which satellite glial cells are involved (visceral pain, nerve regeneration) nor other nutraceuticals or mechanisms of action have been studied. Although more preclinical and clinical research is needed, the available reports support the general notion that nutraceuticals may become interesting alternatives in the prevention and/or treatment of peripheral gliopathies and their associated conditions, including those affecting the satellite glial cells.

The Involvement of the Endogenous Opioid System in the Gastrointestinal Aging in Mice and Humans.

Nearly 20% of elderly patients suffer from constipation, but the age-related changes in the gastrointestinal (GI) tract remain insufficiently elucidated. In this study, the alterations within the endogenous opioid system (EOS) as a potential cause of constipation in the elderly were evaluated. The GI functions were assessed in vitro and in vivo and compared between 6-, 12- and 18-month old mice. Moreover, the effect of opioid receptor (MOP, DOP, KOP) agonists on the mouse GI tract functions and the EOS components expression in mouse tissues and colonic biopsies from patients with functional constipation were determined. In the oldest mice, the GI peristalsis was significantly impaired as compared to the younger groups. The tissue response to MOP and DOP, but not KOP, agonists weakened with age in vitro; for DOP, it was confirmed in vivo. In the mouse upper GI tract, Oprm1, Oprd1, Oprk1 expression decreased with age; in the colon, Oprm1 expression increased. There were no differences in the expression of these genes in the colonic biopsies from patients >50 years old as compared to the younger group. In conclusion, the age-related impairment of the GI peristalsis may result from reduced MOP and DOP response to the activation with opioid agonists or the alterations in the EOS expression.

The Enteric Glia and Its Modulation by the Endocannabinoid System, a New Target for Cannabinoid-Based Nutraceuticals?

The enteric nervous system (ENS) is a part of the autonomic nervous system that intrinsically innervates the gastrointestinal (GI) tract. Whereas enteric neurons have been deeply studied, the enteric glial cells (EGCs) have received less attention. However, these are immune-competent cells that contribute to the maintenance of the GI tract homeostasis through supporting epithelial integrity, providing neuroprotection, and influencing the GI motor function and sensation. The endogenous cannabinoid system (ECS) includes endogenous classical cannabinoids (anandamide, 2-arachidonoylglycerol), cannabinoid-like ligands (oleoylethanolamide (OEA) and palmitoylethanolamide (PEA)), enzymes involved in their metabolism (FAAH, MAGL, COX-2) and classical (CB1 and CB2) and non-classical (TRPV1, GPR55, PPAR) receptors. The ECS participates in many processes crucial for the proper functioning of the GI tract, in which the EGCs are involved. Thus, the modulation of the EGCs through the ECS might be beneficial to treat some dysfunctions of the GI tract. This review explores the role of EGCs and ECS on the GI tract functions and dysfunctions, and the current knowledge about how EGCs may be modulated by the ECS components, as possible new targets for cannabinoids and cannabinoid-like molecules, particularly those with potential nutraceutical use.

GPR18 receptor ­ the structure and the role in the physiology and pathophysiology / Receptor GPR18 ­ struktura i rola w fizjologii oraz patofizjologii.

G-protein coupled receptors constitute the largest family of membrane receptors and they participate in the maintenance of the homeostasis in the body. Some of these receptors still remain orphan receptors as there is insufficient research and ambiguous evidence concerning their function and endogenous ligands. For a long time, GPR18 belonged to this group, but recently it has been classified as an endocannabinoid receptor due to its affinity to cannabinoid ligands. GPR18 receptor is expressed in the encephalon, thyroid gland, leukocytes, lungs and testicles. The modulatory role of GPR18 receptor has been proven in the regulation of intraocular pressure, neuroimmunomodulation, regulation of arterial blood pressure and in metabolic disorders. In this article we summarize the current knowledge concerning the GPR18 receptor ­ its expression, ligands and the in the physiological processes and the pathophysiological conditions.

Nutraceuticals and Enteric Glial Cells.

Until recently, glia were considered to be a structural support for neurons, however further investigations showed that glial cells are equally as important as neurons. Among many different types of glia, enteric glial cells (EGCs) found in the gastrointestinal tract, have been significantly underestimated, but proved to play an essential role in neuroprotection, immune system modulation and many other functions. They are also said to be remarkably altered in different physiopathological conditions. A nutraceutical is defined as any food substance or part of a food that provides medical or health benefits, including prevention and treatment of the disease. Following the description of these interesting peripheral glial cells and highlighting their role in physiological and pathological changes, this article reviews all the studies on the effects of nutraceuticals as modulators of their functions. Currently there are only a few studies available concerning the effects of nutraceuticals on EGCs. Most of them evaluated molecules with antioxidant properties in systemic conditions, whereas only a few studies have been performed using models of gastrointestinal disorders. Despite the scarcity of studies on the topic, all agree that nutraceuticals have the potential to be an interesting alternative in the prevention and/or treatment of enteric gliopathies (of systemic or local etiology) and their associated gastrointestinal conditions.

AdipoRon, an Orally Active, Synthetic Agonist of AdipoR1 and AdipoR2 Receptors Has Gastroprotective Effect in Experimentally Induced Gastric Ulcers in Mice.

INTRODUCTION: Adiponectin is a hormone secreted by adipocytes, which exhibits insulin-sensitizing and anti-inflammatory properties and acts through adiponectin receptors: AdipoR1 and AdipoR2. The aim of the study was to evaluate whether activation of adiponectin receptors AdipoR1 and AdipoR2 with an orally active agonist AdipoRon has gastroprotective effect and to investigate the possible underlying mechanism. METHODS: We used two well-established mouse models of gastric ulcer (GU) induced by oral administration of EtOH (80% solution in water) or diclofenac (30 mg/kg, p.o.). Gastroprotective effect of AdipoRon (dose 5 and 50 mg /kg p.o) was compared to omeprazole (20 mg/kg p.o.) or 5% DMSO solution (control). Clinical parameters of gastroprotection were assessed using macroscopic (gastric lesion area) and microscopic (evaluation of the gastric mucosa damage) scoring. To establish the molecular mechanism, we measured: myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities; glutathione (GSH) level; and IL-1ß, adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK expression in gastric tissue. RESULTS: AdipoRon produced a gastroprotective effect in both GU mouse models as evidenced by significantly lower macroscopic and microscopic damage scores. AdipoRon exhibited anti-inflammatory effect by reduction in MPO activity and IL-1ß expression in the gastric tissue. Moreover, AdipoRon induced antioxidative action, as demonstrated with higher GSH levels, and increased SOD and GPX activity. CONCLUSIONS: Activation of AdipoR1 and AdipoR2 using AdipoRon reduced gastric lesions and enhanced cell response to oxidative stress. Our data suggest that AdipoR1 and AdipoR2 activation may be an attractive therapeutic strategy to inhibit development of gastric ulcers.

The age-related alerations in the enteric nervous system and their impact on peristalsis of the gastrointestinal tract.

Constipation occurs more often in old patients, because the intestinal peristalsis decreases with aging. Constipation is caused due to impaired motility of the intestines, intestinal barrier damage and the imbalance between the absorption and secretion of water and electrolytes, as well as disturbed production and release of intestinal hormones, infiltration of the gastrointestinal tract with immune cells, excessive production of pro-inflammatory cytokines and the alterations in the functions of enteric nervous system. In this review we will discuss the most important issues associated with the process of aging of the digestive tract, focusing on the enteric nervous system.

Opioids in Cancer Development, Progression and Metastasis: Focus on Colorectal Cancer.

OPINION STATEMENT: So far, opioids have been successfully used to reduce cancer pain in patients in order to improve their quality of life. However, the use of opioids leads to numerous side effects such as constipation, drowsiness, nausea, itching, increased sweating and hormonal changes. In this review, we described the action of opioids in several molecular pathways significant for maintenance of the intestinal homeostasis including the impact on the intestinal epithelium integrity, changes in microbiome composition, modulation of the immune system or induction of apoptosis and inhibition of angiogenesis. We summed up the role of individual opioids in the processes involved in the growth and development of cancer and elucidated if targeting opioid receptors may constitute novel therapeutic option in colon cancer.

Antinociceptive potency of a fluorinated cyclopeptide Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2.

Opioid peptides and opiate drugs such as morphine, mediate their analgesic effects, but also undesired side effects, mostly through activation of the mu opioid receptor. However, delta- and kappa-opioid receptors can also contribute to the analgesic effects of opioids. Recent findings showed that simultaneous activation of multiple opioid receptors may result in additional analgesia with fewer side effects. Here, we evaluated the pharmacological profile of our formerly developed mixed mu/kappa-opioid receptor ligands, Dmt-c[D-Lys-Phe-Phe-Asp]NH2 (C-36) and Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2 (F-81). The ability of these peptides to cross the blood-brain barrier was tested in the parallel artificial membrane permeability (PAMPA) assay. On the basis of the hot-plate test in mice after central and peripheral administration, analog F-81 was selected for the anti-nociceptive and anti-inflammatory activity assessment after peripheral administration.