scholarly journals Ketogal Safety Profile in Human Primary Colonic Epithelial Cells and in Mice

2021 ◽  
Vol 14 (11) ◽  
pp. 1149
Author(s):  
Federica Sodano ◽  
Bice Avallone ◽  
Monica Tizzano ◽  
Chiara Fogliano ◽  
Barbara Rolando ◽  
...  

In our previous studies, a ketorolac–galactose conjugate (ketogal) showed prolonged anti-inflammatory and analgesic activity, causing less gastric ulcerogenic effect and renal toxicity than its parent drug ketorolac. In order to demonstrate the safer profile of ketogal compared to ketorolac, histopathological changes in the small intestine and liver using three staining techniques before and after repeated oral administration in mice with ketorolac or an equimolecular dose of its galactosylated prodrug ketogal were assessed. Cytotoxicity and oxidative stress parameters were evaluated and compared in ketorolac- and ketogal-treated Human Primary Colonic Epithelial cells at different concentrations and incubation times. Evidence of mitochondrial oxidative stress was found after ketorolac treatment; this was attributable to altered mitochondrial membrane depolarization and oxidative stress parameters. No mitochondrial damage was observed after ketogal treatment. In ketorolac-treated mice, severe subepithelial vacuolation and erosion with inflammatory infiltrates and edematous area in the intestinal tissues were noted, as well as alterations in sinusoidal spaces and hepatocytes with foamy cytoplasm. In contrast, treatment with ketogal provided a significant improvement in the morphology of both organs. The prodrug clearly demonstrated a safer profile than its parent drug both in vitro and ex vivo, confirming that ketogal is a strategic alternative to ketorolac.

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27452 ◽  
Author(s):  
Barbara Ambruosi ◽  
Manuel Filioli Uranio ◽  
Anna Maria Sardanelli ◽  
Paola Pocar ◽  
Nicola Antonio Martino ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Clarice Noussi Djouwoug ◽  
Florence Tsofack Ngueguim ◽  
Raceline Kamkumo Gounoue ◽  
Clémence Donfack Gouni ◽  
Antoine Kavaye Kandeda ◽  
...  

Bridelia atroviridis Müll. Arg. (B. atroviridis) is a plant used in Cameroonian traditional medicine to manage diabetes. The effects of hydroethanolic barks extract from B. atroviridis were evaluated on diabetes disorders including hematology, inflammatory, and oxidative stress parameters. The in vitro antioxidant capacity of the hydroethanolic bark extract (70 : 30) was evaluated. Nicotinamide-/streptozotocin-induced diabetic rats were daily treated with the B. atroviridis extract for fifteen days. Glycemia were evaluated every 5 days, insulin sensibility test was performed, and haematological, inflammatory, and oxidative stress parameters were analysed. Histomorphometry of the pancreas was realized. The extract was able to scavenge free radicals in vitro and decrease significantly the blood glucose levels. The treatment resulted in a significant alleviation of insulin resistance, anemia, leukocytopenia, and thrombocytopenia observed in untreated diabetic rats. The extract significantly decreased proinflammatory cytokines TNF-α, IL-1β, and IL-10. The rate of reduced glutathione was increased in the pancreas, whereas the catalase activity and nitrite concentration were decreased. Diabetic control showed a reduced size of Langerhans islet, whereas the size of islets was large in treated groups. The hydroethanolic extract of B. atroviridis was able to improve glycemia and alleviate haematological and inflammatory parameters disorders observed in diabetic conditions, probably due to its antidiabetic, anti-inflammatory, and antioxidant capacities.


2019 ◽  
Vol 11 (3) ◽  
pp. 32-40
Author(s):  
Caroline de Souza Araujo ◽  
Dalita Gomes Silva Morais Cavalcante ◽  
Nathália Oliveira Braga ◽  
Andressa Silva Gomes ◽  
Eidi Yoshihara ◽  
...  

The purpose of this study was to assess in vitrocytotoxicity of natural rubber (NR) latex membranes stabilized with different concentrations of ammonia, as well as evaluate possible changes in oxidative stressparameters. To this end, CHO-k1 cells were exposed to NR membranes for 24 h. Cytotoxicity wasassessed by the MTT assay and the oxidative stress parameters were established by glutathione (GSH) and malondialdehyde (MDA) levels. The results show that the ammonia present in the NR latex membranes can deplete cell viability and enhance GSH consumption in the cells. NR latex membranes stabilized with 2.0% of ammonia were cytotoxic to the cell lineage used in this study. From these results, it is possible to infer that the use of ammonia to stabilize NR latex membranes with biomedical purposes has to bedone carefully, to avoid possible harmful effects to human health.


2016 ◽  
Vol 32 (2) ◽  
pp. 519-528 ◽  
Author(s):  
Lara M. Gomes ◽  
Milena Carvalho-Silva ◽  
Letícia J. Teixeira ◽  
Joyce Rebelo ◽  
Isabella T. Mota ◽  
...  

2021 ◽  
Vol 406 ◽  
pp. 113226
Author(s):  
Talita Tuon ◽  
Sandra S. Meirelles ◽  
Airam B. de Moura ◽  
Thayse Rosa ◽  
Laura A. Borba ◽  
...  

Author(s):  
Basiru Olaitan Ajiboye ◽  
Babatunji Emmanuel Oyinloye ◽  
Jennifer Chidera Awurum ◽  
Sunday Amos Onikanni ◽  
Adedotun Adefolalu ◽  
...  

Abstract Objectives The current study evaluates the protective role of aqueous extract of Sterculia tragacantha leaf (AESTL) on pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67 and GLP-1R) and oxidative stress parameters in streptozotocin-induced diabetic rats. Methods Diabetes mellitus was induced into the experimental Wistar animals via intraperitoneal (IP) injection of streptozotocin (35 mg/kg body weight) and 5% glucose water was given to the rats for 24 h after induction. The animals were categorized into five groups of 10 rats each as follows normal control, diabetic control, diabetic rats administered AESTL (150 and 300 mg/kg body weight) and diabetic rats administered metformin (200 mg/kg) orally for two weeks. Thereafter, the animals were euthanized, blood sample collected, pancreas harvested and some pancreatic gene expressions (such as insulin, PCNA, PDX-1, KI-67, and GLP-1R)s as well as oxidative stress parameters were analyzed. Results The results revealed that AESTL significantly (p<0.05) reduced fasting blood glucose level, food and water intake, and lipid peroxidation in diabetic rats. Diabetic rats administered different doses of AESTL showed a substantial upsurge in body weight, antioxidant enzyme activities, and pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67, and GLP-1R). Conclusions It can therefore be concluded that AESTL has the ability to protect the pancreas during diabetes mellitus conditions.


2021 ◽  
Vol 10 (7) ◽  
pp. 1342
Author(s):  
Oliwia Gawlik-Kotelnicka ◽  
Anna Skowrońska ◽  
Aleksandra Margulska ◽  
Karolina H. Czarnecka-Chrebelska ◽  
Igor Łoniewski ◽  
...  

There is a huge need to search for new treatment options and potential biomarkers of therapeutic response to antidepressant treatment. Depression and metabolic syndrome often coexist, while a pathophysiological overlap, including microbiota changes, may play a role. The paper presents a study protocol that aims to assess the effect of probiotic supplementation on symptoms of depression, anxiety and stress, metabolic parameters, inflammatory and oxidative stress markers, as well as fecal microbiota in adult patients with depressive disorders depending on the co-occurrence of metabolic syndrome. The trial will be a four-arm, parallel-group, prospective, randomized, double-blind, controlled design that will include 200 participants and will last 20 weeks (ClinicalTrials.gov identifier: NCT04756544). The probiotic preparation will contain Lactobacillus helveticus Rosell®-52, Bifidobacterium longum Rosell®-175. We will assess the level of depression, anxiety and stress, quality of life, blood pressure, body mass index and waist circumference, white blood cells count, serum levels of C-reactive protein, high-density lipoprotein (HDL) cholesterol, triglycerides, fasting glucose, fecal microbiota composition and the level of some fecal microbiota metabolites, as well as serum inflammatory markers and oxidative stress parameters. The proposed trial may establish a safe and easy-to-use adjunctive treatment option in a subpopulation of depressive patients only partially responsive to pharmacologic therapy.


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