Effect of vitamin D on free radical metabolism in renal tissues of septic rats / Septik ratların böbrek dokularında serbest radikal metabolizmasına vitamin D’nin etkisi

2016 ◽  
Vol 41 (5) ◽  
Author(s):  
Gökçe Atikeler ◽  
Mehmet Zahid Çıracı ◽  
Murat Kocabıyık ◽  
Mustafa Kavutçu ◽  
Orhan Canbolat ◽  
...  

AbstractObjective: Sepsis is a common cause of morbidity and mortality in the intensive care unit. Lipopolysaccharide (LPS)-induced excessive immune response is associated with multi-organ damage in sepsis. Excessive immune response causes multi-organ damage by increasing oxidative stress. Studies on the antioxidant effects of vitamin D demonstrated its protective role. In this study we aimed to investigate the effects of vitamin D on free radical metabolism in LPS injected rats.Methods: Twenty four wistar albino rats were separated into control, sepsis, sepsis+vitamin D and vitamin D groups. Sepsis was induced with single injection of LPS Esherichia coli (O111-b4) 16 mg/kg. Vitamin D was given 2 mg/kg 25 (OH) single dose via gavage for 3 days. Renal function tests were analyzed in serum. Tissue catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione-S-transferase (GST) activities were analyzed, and rat renal tissues were evaluated histopathologically.Results: SOD and GSH-Px activities were not significantly different between the groups. CAT activities were significantly decreased in all groups compared to control, this suppression was seen in the sepsis+vitamin D group versus sepsis group. GST activities were significantly decreased in sepsis and sepsis+vitamin D group compared to control, but GST activities were significantly elevated vitamin D group compare to sepsis and sepsis+vitamin D group. Blood urea nitrogen (BUN) and creatinine levels were significantly elevated in sepsis and sepsis+vitamin D group. Inflammation, expansion in bowman capsule were detected in sepsis and sepsis+vitamin D groups.Conclusion: Vitamin D treatment does not seem to have protective role against renal toxicity in sepsis.Nutrition with vitamin D in sepsis may have suppressive effect on antioxidant enzymes such as CAT and GST due to reduced substrat level which use hydrogen peroxide (H

Author(s):  
Amina Maya Lahneche ◽  
Ratiba Boucheham ◽  
Nassima Boubekri ◽  
Sabah Bensaci ◽  
Sabrina Bicha ◽  
...  

The objective of the present study was to evaluate the protective effect of n-butanol extract of Centaurea sphaerocephala (C.sphaerocephala) and Vitamin E against sodium valproate-induced hepatotoxicity and oxidative stress in male rats. Male rats were divided into eight equal groups treated with plant extract (50mg/kg, 100mg /kg), Vit. E (100mg/kg) and VPA (300mg/kg). At the end of the experiment, animal were scarified and samples (blood and liver’s tissue) were removed isolated for biochemical and histological study. VPA-treated rats showed hepatic injury characterized by a significant increase in biochemical parameters (serum transaminase, cholesterol and triglycerides). Also, VPA induced oxidative stress exhibited a significant increase in MDA level and significant decrease in GSH levels, CAT and GPx activities. These effects were accompanied by histopathological changes in liver. While the pretreatment by n-butanol extract of C. sphaerocephala reversed the alteration induced by VPA and reduced its toxic effects. The results showed a significant decrease in serum markers and liver’s lipid peroxidation whereas GSH level and the activities of GPx, CAT enzymes were significantly increased. Histopathological observations correlated with the biochemical parameters. VPA-induced hepatotoxicity involved free radical production, the antioxidant and free radical scavenging property of Centaurea sphaerocephala would have provided the protection against hepatic damage.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ragavan V. Suresh ◽  
Elizabeth W. Bradley ◽  
Matthew Higgs ◽  
Vincenzo C. Russo ◽  
Maha Alqahtani ◽  
...  

Francisella tularensis (F. tularensis) is a Gram-negative, intracellular bacterium and the causative agent of a fatal human disease known as tularemia. The CDC has classified F. tularensis as a Tier 1 Category A select agent based on its ease of aerosolization, low infectious dose, past use as a bioweapon, and the potential to be used as a bioterror agent. Francisella has a unique replication cycle. Upon its uptake, Francisella remains in the phagosomes for a short period and then escapes into the cytosol, where the replication occurs. Francisella is recognized by cytosolic pattern recognition receptors, Absent In Melanoma 2 (Aim2) and Nacht LRR and PYD domains containing Protein 3 (Nlrp3). The recognition of Francisella ligands by Aim2 and Nlrp3 triggers the assembly and activation of the inflammasome. The mechanism of activation of Aim2 is well established; however, how Nlrp3 inflammasome is activated in response to F. tularensis infection is not known. Unlike Aim2, the protective role of Nlrp3 against Francisella infection is not fully established. This study investigated the role of Nlrp3 and the potential mechanisms through which Nlrp3 exerts its detrimental effects on the host in response to F. tularensis infection. The results from in vitro studies demonstrate that Nlrp3 dampens NF-κB and MAPK signaling, and pro-inflammatory cytokine production, which allows replication of F. tularensis in infected macrophages. In vivo, Nlrp3 deficiency results in differential expression of several genes required to induce a protective immune response against respiratory tularemia. Nlrp3-deficient mice mount a stronger innate immune response, clear bacteria efficiently with minimal organ damage, and are more resistant to Francisella infection than their wild-type counterparts. Together, these results demonstrate that Nlrp3 enhances the host’s susceptibility to F. tularensis by modulating the protective innate immune responses. Collectively, this study advances our understanding of the detrimental role of Nlrp3 in tularemia pathogenesis.


2020 ◽  
Vol 10 (5) ◽  
pp. 578-586
Author(s):  
Areeg M. Abdelrazek ◽  
Shimaa A. Haredy

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu. Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues. Methods and Material: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily. Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10. Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.


2020 ◽  
Vol 10 (01) ◽  
pp. e104-e109
Author(s):  
Antonio Molina-Carballo ◽  
Antonio Emilio Jerez-Calero ◽  
Antonio Muñoz-Hoyos

AbstractMelatonin, produced in every cell that possesses mitochondria, acts as an endogenous free radical scavenger, and improves energetic metabolism and immune function, by complex molecular crosstalk with other intracellular compounds. There is greatly increasing evidence regarding beneficial effects of acute and chronic administration of high melatonin doses, in infectious, developmental, and degenerative pathologies, as an endothelial cell and every cell protectant.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S343-S343
Author(s):  
Andrew David Berti ◽  
Pramodini Kale-Pradhan ◽  
Christopher Giuliano ◽  
Bianca Aprilliano ◽  
Christopher R Miller ◽  
...  

Abstract Background During the early COVID-19 pandemic a large number of investigational agents were utilized due to lack of therapeutic options. We evaluate the utility of commonly-used investigational agents combined with hydroxychloroquine (HCQ). Methods This multicenter observational cohort study included patients admitted with COVID-19 between March - May 2020 in Detroit, Michigan who received at least 2 doses of HCQ. Our primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score from presentation to day 5 of HCQ therapy with a secondary outcome of in-hospital mortality. Data collected included demographics, Charlson Comorbidity index (CCI), daily SOFA score, laboratory data and COVID-directed therapies. Multiple linear regressions were performed to control for potential confounders between different therapies and change in SOFA score. Results Three hundred thirty-five patients receiving HCQ were included. Patients were 62 ± 14.8 years of age, male (54%) and African-American (82%) with a mean CCI of 1.7 ± 1.9. In our cohort, 32% were admitted to the intensive care unit and 35% expired. Therapies received by more than 20% of patients in addition to HCQ included azithromycin (80%), zinc (76%) and vitamin D (29%). In our unadjusted analysis, a significant improvement in SOFA score was observed with zinc (0.76) while no significant change was observed with azithromycin (-0.46) or vitamin D (0.05). However, there was no significant change in SOFA score after adjusting for confounders for azithromycin, zinc and vitamin D. No difference in mortality was observed between the groups. Conclusion Overall, no benefit in end-organ damage or mortality was observed with the addition of azithromycin, zinc or vitamin D to HCQ. Further studies are needed to confirm this observation. Disclosures All Authors: No reported disclosures


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