Chronic Systemic Toxicity Study of Copper Intrauterine Devices in Female Wistar Rats

Zhao, Xiaojie; Liu, Qian; Sun, Haixiang; Hu, Yali; Wang, Zhaoxu

doi:10.12659/msm.902137

Cited by 16 publications

(7 citation statements)

References 24 publications

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“…The ratio of each organ to body weight is relatively constant under normal conditions. However, the organ coefficient would alter with the change of damaged organ weight after animals are poisoned [ 28 ]. The result of organ coefficient was shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

The antiviral activity of kaempferol against pseudorabies virus in mice

Wang

et al. 2021

BMC Vet Res

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Background Pseudorabies virus (PRV), a member of the Alphaherpesviruses, is one of the most important pathogens that harm the global pig industry. Accumulated evidence indicated that PRV could infect humans under certain circumstances, inducing severe clinical symptoms such as acute human encephalitis. Currently, there are no antiviral drugs to treat PRV infections, and vaccines available only for swine could not provide full protection. Thus, new control measures are urgently needed. Results In the present study, kaempferol exhibited anti-PRV activity in mice through improving survival rate by 22.22 %, which was higher than acyclovir (Positive control) with the survival rate of 16.67 % at 6 days post infection (dpi); meanwhile, the survival rate was 0 % at 6 dpi in the infected-untreated group. Kaempferol could inhibit the virus replication in the brain, lung, kidney, heart and spleen, especially the viral gene copies were reduced by over 700-fold in the brain, which was further confirmed by immunohistochemical examination. The pathogenic changes induced by PRV infection in these organs were also alleviated. The transcription of the only immediate-early gene IE180 in the brain was significantly inhibited by kaempferol, leading to the decreased transcriptional levels of the early genes (EPO and TK). The expression of latency-associated transcript (LAT) was also inhibited in the brain, which suggested that kaempferol could inhibit PRV latency. Kaempferol-treatment could induce higher levels of IL-1β, IL-4, IL-6, TNF-α and IFN-γ in the serum at 3 dpi which were then declined to normal levels at 5 dpi. Conclusions These results suggested that kaempferol was expected to be a new alternative control measure for PRV infection.

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Section: Resultsmentioning

confidence: 99%

The antiviral activity of kaempferol against pseudorabies virus in mice

Wang

et al. 2021

BMC Vet Res

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“…Considering that cyclophosphamide was widely used to build the immunocompromised mouse model and the methods are mature, in this study, cyclophosphamide (20 mg/kg) was used as an immunosuppressor to build the immunocompromised mouse model. Changes in bodyweight and organ coefficients can reflect whether the body is in a pathological state [ 41 ]. After cyclophosphamide administration, the bodyweight and organ coefficients of the spleen and thymus decreased significantly, suggesting that the immunocompromised model was successively established.…”

Section: Discussionmentioning

confidence: 99%

The Immunomodulatory Effects of Phellodendri Cortex Polysaccharides on Cyclophosphamide-Induced Immunosuppression in Mice

Cheng

Liu

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Cyclophosphamide is a commonly used anticancer drug, and immunosuppression is one of the most common side effects. How to recover the immunological function is important for cyclophosphamide-treated patients. In the present study, Phellodendri Cortex polysaccharides (CPP) could enhance the proliferation of mouse spleen lymphocytes in vitro. The immunoregulatory function of CPP was then investigated in cyclophosphamide-induced immunosuppressed mice. In CPP-treated groups, mice were orally treated with CPP at doses of 1, 0.5, and 0.25 g/kg bodyweight from 1 to 11 d, respectively. The cyclophosphamide was administrated in CPP and cyclophosphamide groups from 12 to 14 d. In the cyclophosphamide and normal control groups, the mice received equal volume of saline from 1 to 14 d. The results showed that CPP (1 g/kg) could significantly increase the bodyweight of mice, even during cyclophosphamide treatment. The organ coefficients of the spleen and thymus were recovered by CPP treatment. CPP upregulated the contents of cytokines (IL-2, IL-6, IFN-γ, and TNF-α) in serum, which were downregulated by cyclophosphamide. The mRNA levels of these cytokines were also elevated by CPP treatment in the spleen. Cyclophosphamide upregulated the expressions of NF-κB p65, TLR4, and MyD88, suggesting that the NF-κB signaling pathway was activated by cyclophosphamide. After CPP treatment, it was recovered to normal level. These results indicated that CPP alleviated the cyclophosphamide-induced immunosuppression.

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“…Since Cu IUD users generally experience abnormal uterine bleeding or abdominal pain and have not shown clinical signs of toxicity, it is believed that Cu homeostasis mechanisms may be sufficient to prevent the accumulation of this metal. In an animal study, Wistar rats were implanted with Cu IUDs of different doses, with no toxic effects evident [85]. Because they were exposed to much higher Cu levels than those used in humans, the results are reassuring about the Cu IUDs' safety; however, more research is needed.…”

Section: Copper and Pathogenesismentioning

confidence: 99%

Copper in Gynecological Diseases

Conforti,

Delsouc,

Zorychta

et al. 2023

IJMS

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Copper (Cu) is an essential micronutrient for the correct development of eukaryotic organisms. This metal plays a key role in many cellular and physiological activities, including enzymatic activity, oxygen transport, and cell signaling. Although the redox activity of Cu is crucial for enzymatic reactions, this property also makes it potentially toxic when found at high levels. Due to this dual action of Cu, highly regulated mechanisms are necessary to prevent both the deficiency and the accumulation of this metal since its dyshomeostasis may favor the development of multiple diseases, such as Menkes’ and Wilson’s diseases, neurodegenerative diseases, diabetes mellitus, and cancer. As the relationship between Cu and cancer has been the most studied, we analyze how this metal can affect three fundamental processes for tumor progression: cell proliferation, angiogenesis, and metastasis. Gynecological diseases are characterized by high prevalence, morbidity, and mortality, depending on the case, and mainly include benign and malignant tumors. The cellular processes that promote their progression are affected by Cu, and the mechanisms that occur may be similar. We analyze the crosstalk between Cu deregulation and gynecological diseases, focusing on therapeutic strategies derived from this metal.

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Chronic Systemic Toxicity Study of Copper Intrauterine Devices in Female Wistar Rats

Cited by 16 publications

References 24 publications

The antiviral activity of kaempferol against pseudorabies virus in mice

The antiviral activity of kaempferol against pseudorabies virus in mice

The Immunomodulatory Effects of Phellodendri Cortex Polysaccharides on Cyclophosphamide-Induced Immunosuppression in Mice

Copper in Gynecological Diseases

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