Protective Effect of Plumeria Pudica Latex Proteins on Intestinal Mucositis Induced by 5-Fluorouracil.

Intestinal mucositis is characterized by inflammation and ulceration of the mucosa that affects the gastrointestinal tract and is associated with administering some drugs, such as 5- Fluorouracil (5-FU), conventional chemotherapy used in clinics for cancer therapy. Inside intestinal mucosa, the 5-FU acts, leading to oxidative stress, stimulating the production/release of proinflammatory cytokines, local accumulation of neutrophils and consequent tissue damage. These alterations favor bacterial proliferation, triggering secondary infections, and are responsible for undesired effects such as myelosuppression and diarrhea. These factors negatively impact oncological patients' quality of life and explain why they commonly interrupt their treatment prematurely. Currently, there is no specific drug with the ability to completely avoid this condition, so the search for new molecules with pharmacological properties that can be used for preventing or ameliorating intestinal mucositis is important. Plumeria pudica is a plant that produces latexcontaining molecules with therapeutic potential. A protein fraction obtained from this latex (LPPp), which comprises a well-defined mixture of chitinases, proteinases proteinase inhibitors, was demonstrated to have antioxidant and anti-inflammatory activities, preserving tissue glutathione and malondialdehyde concentration, reducing superoxide dismutase and myeloperoxidase activity, and reducing the level of proinflammatory cytokines in different experimental models. Given this scenario, inflammation and oxidative stress are directly involved in the pathogenesis of intestinal mucositis promoted by 5-FU. So, the hypothesis is that LPPp could inhibit these factors to attenuate the cytotoxicity of this pathology associated with 5-FU-treatment. This article brings new insights into the potential of the laticifer proteins extracted from the latex of P. pudica and opens new perspectives for the treatment of this type of intestinal mucositis with LPPp.

Evaluation of mutagenesis, necrosis and apoptosis induced by omeprazole in stomach cells of patients with gastritis.

BACKGROUND: Gastritis is a superficial and prevalent inflammatory lesion that is considered a public health concern once can cause gastric ulcers and gastric cancer, especially when associated with Helicobacter pylori infection. Proton pump inhibitors, such as omeprazole, are the most widely used drugs to treat this illness. The aim of the study was evaluate cytogenetic effects of omeprazole in stomach epithelial cells of patients with gastritis in presence and absence of H. pylori, through cytogenetic biomarkers and catalse and superoxide dismutase analysis. METHODS: The study included 152 patients from the Gastroenterology Outpatient Clinic of Hospital Getúlio Vargas, Teresina-Brazil, that reported continuous and prolonged omeprazole use in doses of 20, 30 and 40 mg/kg. The participants were divided into groups: (1) patients without gastritis (n = 32); (2) patients without gastritis but with OME use (n = 24); (3) patients with gastritis (n = 26); (4) patients with gastritis undergoing OME therapy (n = 26); (5) patients with gastritis and H. pylori (n = 22) and (6) patients with gastritis and H. pylori on OME therapy (n = 22). RESULTS: OME induced cytogenetic imbalance in the stomach epithelium through the formation of micronuclei (group 6 > 1, 2, 3, 4, 5; group 5 > 1, 2, 3; group 4 > 1, 2, 3); bridges (groups 4 and 6 > 1, 2, 3, 5 and group 2 > 3, 5); buds (groups 2,4,6 > , 1, 3, 5); binucleated cells (group 6 > 1, 2, 3, 4, 5; group 4 > 1, 2, 3); (groups 2 and 3 > 1); picnoses (group 6 > 1, 2, 3, 4, 5), groups 2 and 5 > 1, 3; group 4 > 1, 2, 3, 5); cariorrexis (groups 6 and 4 > 1, 2, 3, 5; groups 2, 3, 5 > 1) and karyolysis (groups 2, 4, and 6 > 1, 3, 5; groups 3 and 5 > 1). The OME cytogenetic instability was associated with H. pylori infection, indicating clastogenic/aneugenic effects, chromosomes alterations, gene expression changes, cytotoxicity and apoptosis. CONCLUSIONS: The cytogenetic changescan be attributed to several mechanisms that are still unclear, including oxidative damage, as observed by increased catalase and superoxide dismutase expresion. Positive correlations between antioxidant enzymes were found with micronuclei formation, and were negative for picnoses. Thus, the continuous and prolonged omeprazole use induces genetic instability, which can be monitored through cytogenetic analyzes, as precursor for gastric cancer.

Latex Proteins from Plumeria pudica with Therapeutic Potential on Acetaminophen-Induced Liver Injury.

Liver disease is global health problem. Paracetamol (APAP) is used as an analgesic drug and is considered safe at therapeutic doses, but at higher doses, it causes acute liver injury. N-acetyl-p- Benzoquinone Imine (NAPQI) is a reactive toxic metabolite produced by biotransformation of APAP. NAPQI damages the liver by oxidative stress and the formation of protein adducts. The glutathione precursor N-acetylcysteine (NAC) is the only approved antidote against APAP hepatotoxicity, but it has limited hepatoprotective effects. The search for new drugs and novel therapeutic intervention strategies increasingly includes testing plant extracts and other natural products. Plumeria pudica (Jacq., 1760) is a plant that produces latex containing molecules with therapeutic potential. Proteins obtained from this latex (LPPp), a well-defined mixture of chitinases, proteinases proteinase inhibitors have shown anti-inflammatory, antinociceptive, antidiarrheal effects as well as a protective effect against ulcerative colitis. These studies have demonstrated that LPPp acts on parameters such as Glutathione (GSH) and Malondialdehyde (MDA) concentration, Superoxide Dismutase (SOD) activity, Myeloperoxidase (MPO) activity, and TNF- α IL1-ß levels. Since oxidative stress and inflammation have been reported to affect the initiation and progression of liver injury caused by APAP, it is suggested that LPPp can act on aspects related to paracetamol hepatoxicity. This article brings new insights into the potential of the laticifer proteins extracted from the latex of P. pudica and opens new perspectives for the treatment of this type of liver disease with LPPp.

Antifungal Proteins from Plant Latex.

Latex, a milky fluid found in several plants, is widely used for many purposes, and its proteins have been investigated by researchers. Many studies have shown that latex produced by some plant species is a natural source of biologically active compounds, and many of the hydrolytic enzymes are related to health benefits. Research on the characterization and industrial and pharmaceutical utility of latex has progressed in recent years. Latex proteins are associated with plants' defense mechanisms, against attacks by fungi. In this respect, there are several biotechnological applications of antifungal proteins. Some findings reveal that antifungal proteins inhibit fungi by interrupting the synthesis of fungal cell walls or rupturing the membrane. Moreover, both phytopathogenic and clinical fungal strains are susceptible to latex proteins. The present review describes some important features of proteins isolated from plant latex which presented in vitro antifungal activities: protein classification, function, molecular weight, isoelectric point, as well as the fungal species that are inhibited by them. We also discuss their mechanisms of action.

The anti-inflammatory and antinociceptive activity of albumins from Crotalaria retusa seeds.

Seeds of Crotalaria retusa L. are used in popular medicine because of their pharmacological properties. The albumin fraction obtained from its seeds contains lectin, a protein known to have analgesic and anti-inflammatory properties. Thus, albumins extracted from C. retusa were investigated for their anti-inflammatory and antinociceptive effects. The intraperitoneal administration of different doses of albumins (5, 10 or 20mg/kg) significantly inhibited the mice paw edema induced by carrageenan (maximum inhibition rate of 80.9% at four hours, 20mg/kg), and this event was followed by diminishing paw myeloperoxidase measurements. Albumins (20mg/kg) also inhibited neutrophil migration into the peritoneal cavity induced by carrageenan. However, no effect was observed in the dextran-induced paw edema and abdominal contortions induced by acetic acid. Moreover, albumins (20mg/kg) significantly reduced the second (inflammatory) phase of the licking time induced by formalin. The detection of heammaglutinating activity against human erythrocytes in albumins evidences the presence of lectin in seeds of C. retusa. Our data showed that seeds of C. retusa had anti-inflammatory and antinociceptive properties and such activities are probably due to the inhibitory effect on neutrophil migration of lectin present in albumins.