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Evaluation of prophylactic efficacy of cinnamaldehyde in murine model against Paradendryphiella arenariae mycotoxin tenuazonic acid-induced oxidative stress and organ toxicity.

ABSTRACT: Cinnamaldehyde (Cin) is a natural product obtained from cinnamon and is reported to have a potential anti-fungal, anti-oxidant, anti-inflammatory and anticancer effect. The present study investigated the possible protective role of Cin against tenuazonic acid-induced mycotoxicity in the murine model. Tenuazonic acid (TeA), a toxin produced by Alternaria is a common contaminant in tomato and tomato-based products. Here, Swiss male mice were administered with TeA isolated from Paradendryphiella arenariae (MW504999) (source-tomato) through injection (238 µg/kg BW) and ingestion (475 µg/kg BW) routes for 2 weeks. Thereafter, the prophylaxis groups were treated with Cin (210 mg/kg BW). The experiment was carried out for 8 weeks. The treated groups were compared to the oral and intra-peritoneal experimental groups that received the toxin solely for 8 weeks. Haematological, histopathological and biochemical aspects of the experimental and the control mice were analysed. Sub-chronic intoxication of mice with TeA showed elevated malondialdehyde (MDA), reduced catalase (CAT) and superoxide dismutase (SOD) production; abnormal levels of aspartate transaminase (AST) and alanine transaminase (ALT). Treatment with Cin reversed TeA-induced alterations of antioxidant defense enzyme activities and significantly prevented TeA-induced organ damage. Thus, cinnamaldehyde showed therapeutic effects and toxicity reduction in TeA induced mycotoxicosis.

SUBMITTER: Kumari A

PROVIDER: S-EPMC8484465 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Evaluation of prophylactic efficacy of cinnamaldehyde in murine model against Paradendryphiella arenariae mycotoxin tenuazonic acid-induced oxidative stress and organ toxicity.

Kumari Ankita A Singh Karuna K

Scientific reports 20210930 1

Cinnamaldehyde (Cin) is a natural product obtained from cinnamon and is reported to have a potential anti-fungal, anti-oxidant, anti-inflammatory and anticancer effect. The present study investigated the possible protective role of Cin against tenuazonic acid-induced mycotoxicity in the murine model. Tenuazonic acid (TeA), a toxin produced by Alternaria is a common contaminant in tomato and tomato-based products. Here, Swiss male mice were administered with TeA isolated from Paradendryphiella ar ...[more]

PMID: 34593834

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Project description:IntroductionThis study was designed to assess the protective role of cinnamaldehyde (Cin) against the synergistic effect of tenuazonic acid (TeA) and Freund's adjuvant on different organs of Swiss albino mice.MethodsTeA was administered singly and in combination with Freund's adjuvant intra-peritoneally. The mice were divided into control (vehicle treated), mycotoxicosis-induced (MI) groups, and treatment groups. The route of administration of TeA was intra-peritoneal. The treatment group (FAICT) received Cin orally as a protective agent against TeA-induced mycotoxicosis. The effects on performance, differential leukocyte counts (DLC), and pathological measurements in eight organs (liver, lungs, kidney, spleen, stomach, heart, brain, and testis) were taken into consideration.ResultsThe body weight and feed consumption decreased significantly in the MI groups, which were reversed in the FAICT group. The necropsy observations revealed an increase in the relative organ-to-body weight percentage in the MI groups, which was restored to normal in the FAICT group. Freund's adjuvant enhanced the effects of TeA on DLC. The antioxidant enzymes SOD and CAT decreased, while MDA increased in the MI groups. Caspase-3 activity was reduced in all organs and remained stable in the treatment group. TeA elevated the ALT concentration in the liver and kidneys and the AST in the liver, kidney, heart, and brain tissues. The oxidative stress induced by TeA in the MI groups was ameliorated in the treatment group. Histopathological observations consisted of NASH, pulmonary oedema and fibrosis, renal crystals and inflammation, splenic hyperplasia, gastric ulceration and cyst, cerebral axonopathy, testicular hyperplasia, and vacuolation in the MI groups. However, no such pathology was recorded in the treatment group.DiscussionsThus, it can be concluded that the toxicity of TeA was found to be enhanced when combined with Freund's adjuvant. However, Cin exhibited promising protective effects against TeA + Freund's adjuvant toxicity and reverted the pathological alterations caused by them. Additionally, this study emphasizes Freund's adjuvant's ability to increase mycotoxicity rather than just acting as an immunopotentiator.

Project description:BackgroundImmune-related adverse events (irAEs), characterized by targeted inflammation, occur in up to 60% of patients with melanoma treated with immune checkpoint inhibitors (ICIs). Evidence proved that the baseline peripheral blood profiles of patients at risk for severe irAEs development paralleled clinical autoimmunity. Interleukin (IL)-23 blockade with risankizumab is recommended for cases that are suffering from autoimmune disease, such as autoimmune colitis. However, currently, the role of IL-23 in irAEs onset and severity remains poorly understood.MethodsThe pro-inflammatory cytokines most associated with severe irAEs onset were identified by retrospective analysis based on GSE186143 data set. To investigate the efficacy of prophylactic IL-23 blockade administration to prevent irAEs, refer to a previous study, we constructed two irAEs murine models, including dextran sulfate sodium salt (DSS)-induced colitis murine model and a combined-ICIs-induced irAEs murine model. To further explore the applicability of our findings, murine models with graft-versus-host disease were established, in which Rag2-/-Il2rg-/- mice were transferred with human peripheral blood mononuclear cells and received combined cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1) treatment. Human melanoma cells were xenografted into these mice concomitantly.ResultsHere we show that IL-23 was upregulated in the serum of patients suffering from irAEs after dual anti-CTLA-4 and anti-PD-1 treatment, and increased as a function of irAEs severity. Additionally, Augmented CD4+ Tems may preferentially underlie irAEs onset. Treating mice with anti-mouse IL-23 antibody concomitantly with combined CTLA-4 and PD-1 immunotherapy ameliorates colitis and, in addition, preserves antitumor efficacy. Moreover, in xenografted murine models with irAEs, prophylactic blockade of human IL-23 using clinically available IL-23 inhibitor (risankizumab) ameliorated colitis, hepatitis and lung inflammation, and moreover, immunotherapeutic control of tumors was retained. Finally, we also provided a novel machine learning-based computational framework based on two blood-based features-IL-23 and CD4+ Tems-that may have predictive potential for severe irAEs and ICIs response.ConclusionsOur study not only provides clinically feasible strategies to dissociate efficacy and toxicity in the use of combined ICIs for cancer immunotherapy, but also develops a blood-based biomarker that makes it possible to achieve a straightforward and non-invasive, detection assay for early prediction of irAEs onset.

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Evaluation of prophylactic efficacy of cinnamaldehyde in murine model against Paradendryphiella arenariae mycotoxin tenuazonic acid-induced oxidative stress and organ toxicity.

Publications

Evaluation of prophylactic efficacy of cinnamaldehyde in murine model against Paradendryphiella arenariae mycotoxin tenuazonic acid-induced oxidative stress and organ toxicity.

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