Thymoquinone protects against 5-Fluorouracil-induced mucositis by NF-κß and HIF-1 mechanisms in mice.

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.

Thymoquinone Improved Nonylphenol-Induced Memory Deficit and Neurotoxicity Through Its Antioxidant and Neuroprotective Effects.

Nonylphenol (NP), a well-known endocrine-disrupter chemical, has several harmful effects on the central nervous system including neuroendocrine disruption, cognitive impairment, and neurotoxicity. Thymoquinone (TQ) is a main bioactive compound in the black seeds of Nigella sativa that has antioxidant, anti-inflammatory, and neuroprotective properties. Here, we investigated the neuroprotective effect of TQ against NP-induced memory deficit and neurotoxicity in rats. To induce memory impairment, NP (25 mg/kg) was used as gavage in male Wistar rats for 21 days. TQ (2.5, 5, and 10 mg/kg) was intraperitoneally administered in NP-treated animals. The morris water maze test was performed to assess spatial learning and memory. The hippocampal tissues were isolated from the brain for histopathological evaluation. Biochemical, molecular, and cellular tests were performed to quantify oxidant (malondialdehyde; MDA)/antioxidant (superoxide dismutase (SOD), total antioxidant capacity (TAC), and reduced glutathione (GSH) parameters) as well as markers for astrocytic activation (glial fibrillary acidic protein; GFAP) and neuronal death (alpha-synuclein; α-syn). Results showed TQ (5 mg/kg) significantly improved NP-induced memory impairment. Histological data revealed a significant increase in the number of necrotic cells in hippocampus, and TQ treatment markedly decreased this effect. The GSH and TAC levels were significantly increased in TQ-treated groups compared to NP group. The molecular analysis indicated that NP increased GFAP and decreased α-syn expression and TQ treatment did the reverse. In vitro study in astrocytes isolated from mice brain showed that TQ significantly increased cell viability in NP-induced cytotoxicity. This study strongly indicates that TQ has neuroprotective effects on NP-induced neurotoxicity through reducing oxidative damages and neuroinflammation. This study investigates the behavioral neurotoxicity induced by Nonylphenol (NP) and the protective effects of Thymoquinone (TQ) as a potent antioxidant compound using molecular, cell culture, histopathological and biochemical techniques.

The protective effects of quercetin nano-emulsion on intestinal mucositis induced by 5-fluorouracil in mice.

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.

Protective Effect of Quercetin Nanoemulsion on 5-Fluorouracil-Induced Oral Mucositis in Mice.

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.

The Investigation into Neurotoxicity Mechanisms of Nonylphenol: A Narrative Review.

BACKGROUND: Nonylphenol (NP), a chemical compound widely used in industry, is the result of the nonylphenol ethoxylate decomposition and it is known as an estrogen-like compound. Numerous studies and researches have shown that it has many destructive functions of various organs such as the brain. This toxicant causes oxidative stress in the cortex and hippocampus cells, which are two essential regions to preserve memory and learning in the brain. METHODS: This review examines recent findings to better understanding the mechanisms of NP neurotoxicity. We used Scopus, Google Scholar, and PubMed databases to find articles focused on the destructive effects of NP on the oxidative stress pathway and its defense mechanisms. RESULTS: NP has potential human health hazards associated with gestational, peri- and postnatal exposure. NP can disrupt brain homeostasis in different ways, such as activation of inflammatory factors in brain especially in hippocampus and cortex, disruption of the cell cycle, changes in neuron, dendrites and synapses morphology, disruption of extra and intracellular calcium ion balance and also memory and learning disorders.

Frequency and epidemiologic aspects of male infertility.

According to different geographical conditions, human health in different sub-regions of the world and cultural differences, the male factor infertility has heterogeneous causes in the world. This study was performed in an attempt to clarify the associated factors which might play a role in this respect in a group of Iranian infertile men. This study was a cross - sectional, descriptive and retrospective study. The information was obtained from the men who had attended the clinic from March 2004-2006. The factors which were studied in this research are the demographic characteristics, smoking, addiction, alcohol drinking, and exposure to lead, cimetidine and history of surgery. In 23.7 % of couples the cause of infertility was pure male factor and in 19.3 % of them the problem was related to male and female factor both. The most important associated factors for male factor included smoking (29%) and history of varicocele operation (22%). Since the quality of individual and social life is related to fertility state, it seems that more comprehensive studies on factors affecting male fertility at the community level are justified and recommended.