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1.
Med Oncol ; 41(6): 148, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733486

ABSTRACT

Numerous herbal products have been the subject of research regarding their potential role in cancer prevention or adjuvant therapy. Pistacia atlantica and its main phytochemicals have garnered significant attention for their potential anti-cancer effects. The study aimed to assess the growth inhibitory effects of P. atlantica essential oil (PAEO) on MKN-45 and AGS cells. This study quantified the volatile compounds in PAEO using Gas Chromatography-Mass Spectrometry (GC-MS). Subsequently, MKN-45 and AGS cells were treated with varying concentrations of PAEO (5%, 2.5%, 1.25%, 0.625%, 0.3125%, 0.156%, 0.0781%, 0.0391%, 0.0195%) for 24 h. Cell viability was evaluated through the MTT assay. The impact of PAEO on gene expression was investigated by quantifying the mRNA levels of Bax and Bcl2 in the various experimental groups using quantitative Real-Time PCR (qRT-PCR) analysis. Additionally, flow cytometry was utilized to evaluate apoptosis in the treated cells. The analysis of PAEO revealed that α-pinene was the predominant monoterpene, constituting 87.9% of the oil composition. The cytotoxic effects of PAEO were evaluated, and it was found that the oil significantly reduced the viability of MKN-45 and AGS cells. The IC50 for MKN-45 cells was determined to be 1.94 × 10-3% after 24 h of treatment, while for AGS cells the IC50 was 2.8 × 10-3% after 24 h. Additionally, the research revealed that PAEO triggered a notable rise in apoptotic cells in both AGS and MKN-45 cell lines. Moreover, at the molecular level, the findings indicated an increase in Bax expression and a decrease in Bcl2 mRNA expression, providing further evidence of the induction of apoptosis in both MKN-45 and AGS cell lines following PAEO treatment. The findings of this study offer evidence supporting the cytotoxic effects of PAEO on gastric cancer cell lines by promoting apoptosis. The findings suggest that PAEO may offer potential as a therapeutic candidate in managing and treating gastric cancer.


Subject(s)
Apoptosis , Cell Survival , Oils, Volatile , Pistacia , Stomach Neoplasms , Humans , Oils, Volatile/pharmacology , Pistacia/chemistry , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , Cell Line, Tumor , Apoptosis/drug effects , Cell Survival/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , bcl-2-Associated X Protein/metabolism , bcl-2-Associated X Protein/genetics , Gas Chromatography-Mass Spectrometry
2.
Front Immunol ; 15: 1339714, 2024.
Article in English | MEDLINE | ID: mdl-38571951

ABSTRACT

The intricate balance of immune reactions towards invading pathogens and immune tolerance towards self is pivotal in preventing autoimmune diseases, with the thymus playing a central role in establishing and maintaining this equilibrium. The induction of central immune tolerance in the thymus involves the elimination of self-reactive T cells, a mechanism essential for averting autoimmunity. Disruption of the thymic T cell selection mechanisms can lead to the development of autoimmune diseases. In the dynamic microenvironment of the thymus, T cell migration and interactions with thymic stromal cells are critical for the selection processes that ensure self-tolerance. Thymic epithelial cells are particularly significant in this context, presenting self-antigens and inducing the negative selection of autoreactive T cells. Further, the synergistic roles of thymic fibroblasts, B cells, and dendritic cells in antigen presentation, selection and the development of regulatory T cells are pivotal in maintaining immune responses tightly regulated. This review article collates these insights, offering a comprehensive examination of the multifaceted role of thymic tissue homeostasis in the establishment of immune tolerance and its implications in the prevention of autoimmune diseases. Additionally, the developmental pathways of the thymus are explored, highlighting how genetic aberrations can disrupt thymic architecture and function, leading to autoimmune conditions. The impact of infections on immune tolerance is another critical area, with pathogens potentially triggering autoimmunity by altering thymic homeostasis. Overall, this review underscores the integral role of thymic tissue homeostasis in the prevention of autoimmune diseases, discussing insights into potential therapeutic strategies and examining putative avenues for future research on developing thymic-based therapies in treating and preventing autoimmune conditions.


Subject(s)
Autoimmune Diseases , Thymus Gland , Humans , Immune Tolerance , Autoimmune Diseases/prevention & control , Self Tolerance , Homeostasis
3.
Saudi Pharm J ; 31(8): 101672, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37448841

ABSTRACT

5-Fluorouracil (5FUra) is the third most popular chemotherapeutic component employed to treat solid tumors. In the present study, we aimed to appraise the silymarin (SM) and silymarin nanoemulsion (SMN) effect on 5FUra-induced gastrointestinal toxicity in adult male rats. A total of 30 male Wistar rats were divided into 6 groups including the control (Crl) group, and groups treated with SMN (5 mg.kg-1), SM (5 mg.kg-1), 5FUra + SMN (5 mg.kg-1), and 5FUra + SM (5 mg.kg-1) by IP injection for 14 days. And gastrointestinal toxicity was induced by a single intraperitoneal (IP) injection of 5FUra (100 mg.kg-1) for the last group in the study. Treating rats with SM and SMN diminished elevating malondialdehyde (MDA) levels, and improved total antioxidant capacity (TAC) levels. Also, the intensity of mRNA expression of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-α) caused by 5FUra in the gastrointestinal tissue tract, and macroscopic oral ulcerations decreased, ass well as weight loss was prevented, particularly in the SMN group. Moreover, in the microscopic scope, there were significant improvements in the levels of hyperemia, hyaline, and inflammatory cell infiltration in the tongue, esophagus, and intestinal tissues in the FUra + SMN and FUra + SM groups compared to 5FUra. Hence, treatment with SM and SMN reduced oxidative stress, histopathological degeneration, and gene expression of inflammatory markers in the gastrointestinal tract. According to the results, treatment with SM and SMN markedly decreases the gastrointestinal toxicity caused by 5FUra.

4.
J Biochem Mol Toxicol ; 37(9): e23405, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37338137

ABSTRACT

Mucositis is among the most common side effects of 5-Fluorouracil (5-FU) and other cancer therapeutic drugs. Thymoquinone (TQ), a bioactive constituent extracted from Nigella sativa, has antioxidant and anti-inflammatory properties and can modify acute gastrointestinal injury. To investigate the effects of TQ on mucositis induced by 5-FU, studied animals were divided into four groups: control, 5-FU unit dose (300 mg/kg) to cause oral and intestinal mucositis (OM and IM), TQ (2.5 mg/kg) and TQ (2.5 mg/kg) plus 5-FU. Due to The molecular mechanisms, it was confirmed that the expression of NF-κß and HIF-1 increases in OM. The serum levels of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), as well as pathological parameters, were assessed. Based on our results, the nuclear factor-kappa ß gene expression in the tongue was downregulated significantly in the 5-FU + TQ compared to the 5-FU. TQ treatment can diminish MDA, and a reduction in oxidative stress was shown. TQ could also reduce the severity of tissue destruction and damaging effects induced by 5-FU on the tongue and intestine. We also observed lower villus length and width in the intestine of the 5-FU group compared to the control group. According to our research's pathological, biochemical, and molecular results, treatment with TQ as an anti-inflammatory and antioxidant compound may be the potential to improve and treat 5-FU-induced OM and IM, and TQ could be used against cancer treatment drugs and exhibit fewer adverse effects.


Subject(s)
Antineoplastic Agents , Mucositis , Mice , Animals , Fluorouracil/toxicity , Antioxidants/pharmacology , Antioxidants/metabolism , Mucositis/chemically induced , Mucositis/drug therapy , Mucositis/prevention & control , Antineoplastic Agents/pharmacology , Oxidative Stress
5.
Viruses ; 15(3)2023 03 18.
Article in English | MEDLINE | ID: mdl-36992490

ABSTRACT

Autoimmune diseases (AIDs) are the consequence of a breach in immune tolerance, leading to the inability to sufficiently differentiate between self and non-self. Immune reactions that are targeted towards self-antigens can ultimately lead to the destruction of the host's cells and the development of autoimmune diseases. Although autoimmune disorders are comparatively rare, the worldwide incidence and prevalence is increasing, and they have major adverse implications for mortality and morbidity. Genetic and environmental factors are thought to be the major factors contributing to the development of autoimmunity. Viral infections are one of the environmental triggers that can lead to autoimmunity. Current research suggests that several mechanisms, such as molecular mimicry, epitope spreading, and bystander activation, can cause viral-induced autoimmunity. Here we describe the latest insights into the pathomechanisms of viral-induced autoimmune diseases and discuss recent findings on COVID-19 infections and the development of AIDs.


Subject(s)
Autoimmune Diseases , COVID-19 , Virus Diseases , Humans , COVID-19/complications , Autoimmune Diseases/epidemiology , Autoimmune Diseases/genetics , Virus Diseases/complications , Virus Diseases/epidemiology , Autoimmunity , Autoantigens
6.
Arch Pharm (Weinheim) ; 355(7): e2200060, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35411625

ABSTRACT

5-Fluorouracil (5-FU)-associated cardiotoxicity has been ranked as the second most common cause of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. In the present study, we investigated the protective impacts of silymarin (SIL) and silymarin nanoemulsion (SLN) against cardiotoxicity caused by 5-FU in rats. Thirty male Wistar rats were divided into six groups as follows: control, SLN (5 mg/kg), SIL (5 mg/kg), 5-FU + SLN, 5-FU + SIL, and 5-FU. Cardiotoxicity was induced by a single intraperitoneal injection of 5-FU (100 mg/kg). The control group received an intraperitoneal injection (ip) of normal saline and the treatment groups received ips of SIL and SLN for 14 days. 5-FU resulted in significant cardiotoxicity, represented by an increase in the serum levels of cardiac enzymes and malondialdehyde, as well as cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) expression, and histopathological degeneration. 5-FU treatment also induced a decrease in body weight, total antioxidant capacity (TAC), and catalase values. Evaluation of electrocardiographic parameters in 5-FU-treated rats showed increases in the ST segment, QRS duration, and RR interval. Treatment with SIL and SLN reduced oxidative stress, cardiac enzymes, histopathological degeneration, and the expression of TNF-α and COX-2 in cardiac tissue. Our results demonstrated that treatment with SIL and SLN significantly improved cardiotoxicity induced by 5-FU in rats.


Subject(s)
Cardiotoxicity , Silymarin , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Cardiotoxicity/drug therapy , Cardiotoxicity/etiology , Cyclooxygenase 2/metabolism , Fluorouracil , Male , Oxidative Stress , Rats , Rats, Wistar , Silymarin/pharmacology , Silymarin/therapeutic use , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/metabolism
7.
Oxid Med Cell Longev ; 2022: 6194532, 2022.
Article in English | MEDLINE | ID: mdl-35126817

ABSTRACT

Background and Objective. 5-Fluorouracil is one of the most common chemotherapeutic agents used in the treatment of solid tumors. 5-Fluorouracil-associated cardiotoxicity is the second cause of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Colchicine is a strong anti-inflammatory drug used to prevent and treat acute gout and treat familial Mediterranean fever. And also, its protective effects on cardiovascular disease have been reported in various studies. The current study is aimed at appraising the effect of colchicine on 5-fluorouracil-induced cardiotoxicity in rats. Methods. Twenty male Wistar rats were divided into four groups as follows: control, 5-fluorouracil, colchicine (5 mg/kg), and 5-fluorouracil+5 mg/kg colchicine. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-fluorouracil (100 mg/kg). The control group received normal saline, and the treatment groups received colchicine with an intraperitoneal injection for 14 days. Findings. 5-Fluorouracil resulted in significant cardiotoxicity represented by an increase in cardiac enzymes, malondialdehyde levels, cyclooxygenase-2 and tumor necrosis factor-alpha expression, cardiac enzymes, and histopathological degenerations. 5-Fluorouracil treatment also decreased body weight, total antioxidant capacity and catalase values, blood cells, and hemoglobin levels. In addition, 5-fluorouracil disrupted electrocardiographic parameters, including increased elevation in the ST segment and increased QRS duration. Treatment with colchicine reduced oxidative stress, cardiac enzymes, histopathological degenerations, and cyclooxygenase-2 expression in cardiac tissue, improved electrocardiographic disorders, and enhanced the number of blood cells and total antioxidant capacity levels. Moreover, body weight loss was hampered after treatment with colchicine. Our results demonstrated that treatment with colchicine significantly improved cardiotoxicity induced by 5-fluorouracil in rats.


Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Antioxidants/administration & dosage , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/drug therapy , Colchicine/administration & dosage , Colchicum/chemistry , Fluorouracil/adverse effects , Phytochemicals/administration & dosage , Phytotherapy/methods , Plant Extracts/administration & dosage , Animals , Antimetabolites, Antineoplastic/administration & dosage , Cardiotoxicity/drug therapy , Cardiotoxicity/etiology , Cardiovascular Diseases/enzymology , Cyclooxygenase 2/metabolism , Fluorouracil/administration & dosage , Male , Myocardium/enzymology , Oxidative Stress/drug effects , Rats , Rats, Wistar , Signal Transduction/drug effects , Treatment Outcome , Tumor Necrosis Factor-alpha/metabolism
8.
Biomed Res Int ; 2022: 2273000, 2022.
Article in English | MEDLINE | ID: mdl-35198633

ABSTRACT

BACKGROUND: Fluorouracil (5-FU) is the third most common chemotherapeutic agent used in the treatment of solid tumors. 5-FU-associated cardiotoxicity ranks the second causes of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Kaempferol (KPF), a common flavonoid, possessing anti-inflammatory, antiapoptotic, antioxidative properties, and its protective effects on cardiovascular disease has been reported in various studies. The current study is aimed at appraising the effect of KPF and KPF nanoparticles (NPs) on 5-FU-induced cardiotoxicity in rats. METHODS: Thirty Male Wistar rats were divided into five groups as follows: control, 5-FU, 5-FU+10 mg/kg vitamin C, 5-FU+ 1 mg/kg KPF, and 5-FU+ 1 mg/kg KPF-NPs. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-FU (100 mg/kg). The control group received normal saline, and the treatment groups received KPF and KPF-NPs with an intraperitoneal injection for 14 days. Each heart histopathological lesions were given a score of 0 to 3 in compliance with the articles for statistical analysis. RESULTS: 5-FU resulted in a significant cardiotoxicity represented by an increase in cardiac enzymes, MDA (malondialdehyde) levels, COX-2 (cyclooxygenase-2) expression, and histopathological degenerations. 5-FU treatment also decreased body weight, TAC (total antioxidant capacity) values, VEGF (vascular endothelial growth factor) expression, blood cells, and hemoglobin (Hb) levels. Treatment with KPF and KPF-NPs reduced oxidative stress, cardiac enzymes, COX-2 expression, and VEGF expression. The number of blood cells, Hb levels, and histopathological degenerations, in cardiac tissue also body weight of animals, increased, followed by treatment with KPF and KPF-NPs. CONCLUSION: Our results demonstrated that treatment with KPF and KPF-NPs significantly improved cardiotoxicity induced by 5-FU in rats.


Subject(s)
Cardiotoxicity/prevention & control , Fluorouracil/toxicity , Kaempferols/pharmacology , Animals , Biomarkers/metabolism , Male , Nanoparticles , Rats , Rats, Wistar
9.
Biochem Biophys Res Commun ; 585: 75-81, 2021 12 31.
Article in English | MEDLINE | ID: mdl-34800883

ABSTRACT

BACKGROUND: Intestinal mucositis is one of chemotherapeutics' most common adverse effects, such as 5-fluorouracil (5-FU). Quercetin (QRC), a naturally occurring flavonoid, has approved antioxidant and anti-inflammatory properties. Thus, in this article, the preventive and curative effects of emulsion and nano-emulsion formulations of QRC were investigated in a model of 5-FU-induced intestinal mucositis using biochemical, histopathological, and molecular approaches. METHOD: Thirty-six mice were divided into six different groups: Control (normal saline), 5-FU (a single dose of 5-FU 300 mg/kg), pre-treatment groups (pre-QRC, and pre-QRC-nano, receiving QRC 5 mg/kg emulsion and nano-emulsion before the induction of mucositis, respectively), and post-treatment groups (post-QRC, and post-QRC-nano, receiving QRC 5 mg/kg emulsion and nano-emulsion after the induction of mucositis, respectively). FINDING: The administration of quercetin emulsion and nano-emulsion could significantly alleviate the oxidant-antioxidant balance of mice serum samples and reverse the destructive histopathologic changes induced by 5-FU in the intestine tissue. Nevertheless, although the expression of both pro-inflammatory genes, NF-κB and HIF-1α, was decreased when quercetin was administered to mice, this reduction was not statistically significant. CONCLUSION: The administration of quercetin emulsion and nano-emulsion formulations could ameliorate the oxidative damage induced by chemotherapeutics, such as the 5-FU. Therefore, if confirmed in further studies, it could be used in clinical settings as a preventive and curative agent to decrease such catastrophic adverse events in chemotherapy patients.


Subject(s)
Emulsions/chemistry , Intestinal Mucosa/drug effects , Mucositis/prevention & control , Nanoparticles/chemistry , Quercetin/pharmacology , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Catalase/metabolism , Fluorouracil , Gene Expression/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Male , Malondialdehyde/metabolism , Mice , Mucositis/chemically induced , Mucositis/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Oxidative Stress/drug effects , Protective Agents/pharmacology , Quercetin/chemistry
10.
J Oncol ; 2021: 5598230, 2021.
Article in English | MEDLINE | ID: mdl-34211552

ABSTRACT

The target of this study was to evaluate the efficacy, histopathological, oxidative stress, and molecular effects of quercetin (QRC) in mice with oral mucositis induced by 5-fluorouracil (5-FU). Thirty-six albino male mice with oral mucositis induced by 5-FU as a chemotherapeutic agent were used in this study. The animals were randomly divided into 6 groups: control group, mucositis (MUC) group, pretreatment group, posttreatment group, and two last groups including nanoemulsion form of QRC with a dose of 5 mg/kg in both pretreatment and posttreatment. In the present evaluation, fewer oral lesions were observed in the QRC posttreatment groups compared to the pretreatment and nanoemulsion receiving groups. In the SOD assay, the most significant difference was observed in the posttreatment nanogroup (41.073 ± 1.24) and pretreatment nanogroup (43.453 ± 2.60) in comparison to the 5-FU group (30.897 ± 1.93). The results of CAT assay also showed a significant difference in nano-posttreatment (124.60 ± 10.85), posttreatment (135.4 ± 9.82), and nano-pretreatment groups (128.80 ± 7.20) compared to the 5-FU group (55.07 ± 8.91). The expression of inflammatory genes such as Hif-1α and NfκB in this group was lower than in the other groups, although this difference was not significant. It seems that the use of QRC can improve the treatment process of oral mucositis induced by 5-FU.

11.
J Cell Physiol ; 236(2): 824-838, 2021 02.
Article in English | MEDLINE | ID: mdl-32617971

ABSTRACT

Polycystic ovary syndrome (PCOS) is the most common hormonal imbalance disease in reproductive-aged women. Its basic characteristics are ovulatory dysfunction and ovarian overproduction of androgens that lead to severe symptoms such as insulin resistance, hirsutism, infertility, and acne. Notwithstanding the disease burden, its underlying mechanisms remain unknown, and no causal therapeutic exists. In recent years, further studies showed that inflammation processes are involved in ovulation and play a key role in ovarian follicular dynamics. Visceral adipose tissue can cause inflammatory response and maintenance of the inflammation state in adipocytes by augmented production of inflammatory cytokines, monocyte chemoattractant proteins, and recruitment of the immune cell. Therefore, the PCOS can be related to a low-grade inflammation state and inflammatory markers. Investigating the inflammatory processes and mediators that contribute to the commencement and development of PCOS can be a critical step for better understanding the pathophysiology of the disease and its treatment through inhibition or control of related pathways. In the present review, we discuss the pathophysiological roles of chronic low-grade inflammation mediators including inflammasome-related cytokines, interleukin-1ß (IL-1ß), and IL-18 in PCOS development.


Subject(s)
Inflammation Mediators/metabolism , Inflammation/metabolism , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/pathology , Animals , Biomarkers/metabolism , Female , Humans , Inflammation/pathology , Signal Transduction/physiology
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