Immunotoxic effect of low dose cisplatin in mice.

Kouchi, Yasuhide; Maeda, Yasuhiro; Ohuchida, Akinobu; Ohsawa, Motoyasu

doi:10.2131/jts.21.4_227

Cited by 16 publications

(6 citation statements)

References 8 publications

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“…As we expected, notable bone marrow suppression and leukopenia were observed 5 days after cisplatin injection, and these pathologic conditions were considerably reserved by RVX treatment, especially at the highest dose of 100 mg/kg. In addition to the bone marrow, the spleen and thymus are representative immune organs, and losses in their weights in experimental models of cisplatin injection have been widely reported [ 37 ], significantly attenuated by RVX treatment in our current study. These findings anticipated that RVX may have potential for use against immunosuppression caused by chemotherapy.…”

Section: Discussionsupporting

confidence: 51%

Antiemetic and Myeloprotective Effects ofRhus verniciflua Stokein a Cisplatin-Induced Rat Model

Kim

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Rhus verniciflua Stoke has been commonly used in traditional medicine to treat gastrointestinal (GI) dysfunction diseases. In order to investigate pharmacological properties of Rhus verniciflua Stoke water extract (RVX) on cisplatin-induced amnesia, RVX (0, 25, 50, or 100 mg/kg) was orally administrated for five consecutive days after a single intraperitoneal injection of cisplatin (6 mg/kg) to SD rat. Cisplatin injection significantly increased the kaolin intake (emesis) but reduced the normal diet intake (anorexia) whereas the RVX treatment significantly improved these abnormal diet behaviors at both the acute and delayed phase. The serotonin concentration and the related gene expressions (5-HT3 receptors and SERT) in small intestine tissue were abnormally altered by cisplatin injection, which were significantly attenuated by the RVX treatment. Histological findings of gastrointestinal tracts, as well as the proteins level of proinflammatory cytokines (TNF-α, IL-6, and IL-1β), revealed the beneficial effect of RVX on cisplatin-induced gastrointestinal inflammation. In addition, RVX significantly improved cisplatin-induced myelosuppression, as evidenced by the observation of leukopenia and by histological examinations in bone marrow. Our findings collectively indicated Rhus verniciflua Stoke improved the resistance of rats to chemotherapy-related adverse effects in the gastrointestinal track and bone marrow.

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Section: Discussionsupporting

confidence: 51%

Antiemetic and Myeloprotective Effects ofRhus verniciflua Stokein a Cisplatin-Induced Rat Model

Kim

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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“…Levels of IL-5 were markedly lowered (58%) by cisplatin treatment, indicating that cisplatin may contribute to some negative biological and immunological side effects; the immunosuppressive effect of cisplatin has been reported in previous studies [29,30]. Our finding suggests that reduction of IL-5 may contribute, in part to the immunotoxic effect of cisplatin.…”

Section:  Il-12 (P70) and Il-5supporting

confidence: 80%

Enhancement of Bone Marrow CD41+ Megakaryocytes as well as Modulation of TNF-a, IL-12, and IL-5 by a Novel Small Molecule, UTL-5g, in Mice Treated with Cisplatin

Valeriote¹,

Chen²,

Media³

et al. 2015

Am. J. Biomed. Sci.

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UTL-5g is a novel small-molecule chemoprotective agent against cisplatin-induced host cytotoxicity. Recent studies showed that UTL-5g increased the blood platelet count, which was reduced in cisplatintreated mice. In order to have a better understanding about the mechanism of action by which UTL-5g promotes platelet production, BDF1 mice were treated with or without UTL-5g after cisplatin treatment; several hematological analyses were conducted. The results showed that treatment of mice with UTL-5g alone by either i.p. injection or oral gavage markedly increased platelet counts. UTL-5g also restored bone marrow cell counts that were reduced by cisplatin treatment. Flow cytometric analysis showed that bone marrow CD41+ megakaryocytic cells were significantly increased in animals pretreated with UTL-5g before cisplatin. Measurement of secreted cytokines showed that pretreatment of UTL-5g lowered blood levels of both TNF- and IL-12 (p70) elevated by cisplatin treatment. On the other hand, pretreatment of UTL-5g raised blood levels of IL-5 that were lowered by cisplatin treatment. The results also showed that 60 mg/kg is the optimal dose of UTL-5g by oral route for the protection of bone marrow cells, CD41+ megakaryocytes, and platelets. In conclusion, this study suggests that UTL-5g (by i.p. injection or oral gavage) enhances the production of platelets by either protecting or increasing bone marrow CD41+ megakaryocytic cells at least in part; UTL-5g also modulates TNF-, IL-12 (p70), and IL-5. Taken together, these observed effects of UTL-5g on megakaryocytes and cytokines play important roles in the chemoprotective properties of UTL5g.

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“…Li et al [30] showed that cisplatin can induce immunosuppressive effects through inhibition of T cell activity. Additionally, Kouchi et al [31] reported that cisplatin blocked splenic T lymphocyte function more than splenic B lymphocyte function.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of Echinacea purpurea (Immulant) against cisplatin-induced immunotoxicity in rats

et al. 2019

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Purpose Cisplatin, one of the most effective anticancer drugs, is known to cause undesirable adverse effects, including immunotoxicity. Echinacea purpurea is an important medicinal plant with immunostimulatory and anti-inflammatory activities. We have investigated the protective effect of an herbal formulation (Immulant) containing E. purpurea extract against cisplatininduced immunotoxicity in rats. Methods Forty mature albino rats were randomized into four groups (10 rats/group). Control (group 1) animals were subjected to intraperitoneal (i.p.) injection of saline solution (0.2 ml) once every 3 days. Group 2 animals received cisplatin (3.5 mg/kg, i.p.) once every 3 days for successive 2 weeks. Group 3 rats received oral Immulant (150 mg/kg) once daily for 2 weeks. Group 4 animals received oral Immulant treatment as in group 3 in addition to cisplatin as in group 2. Serum level of total protein and albumin, total and differential leukocytic count, phagocytic activity of monocytes, humoral activity and splenic histopathology and immunohistochemistry were used as diagnostic markers of immunotoxicity. Results Cisplatin induced marked inhibition of cellular immunity as exhibited by significant decrease of leukocytic count, lymphocyte percentage and phagocytic activity with marked increase in neutrophil percentage. Humoral immunity represented by marked inhibition in total protein and γ-globulin concentration and significant inhibition in antibody titer against Mycoplasma gallisepticum were recorded. Histopathological and immunohistochemical observation of the spleen of cisplatin-treated rats revealed obvious pathological findings of marked depletion and degeneration of lymphoid tissue. Co-oral administration of Immulant resulted in substantial improvement of various immunotoxicological indices compared to cisplatin control. Conclusion The herbal medicine Immulant is an immunostimulant which could be used to treat the immunotoxic effects of cisplatin.

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Immunotoxic effect of low dose cisplatin in mice.

Cited by 16 publications

References 8 publications

Antiemetic and Myeloprotective Effects ofRhus verniciflua Stokein a Cisplatin-Induced Rat Model

Antiemetic and Myeloprotective Effects ofRhus verniciflua Stokein a Cisplatin-Induced Rat Model

Enhancement of Bone Marrow CD41+ Megakaryocytes as well as Modulation of TNF-a, IL-12, and IL-5 by a Novel Small Molecule, UTL-5g, in Mice Treated with Cisplatin

Protective effect of Echinacea purpurea (Immulant) against cisplatin-induced immunotoxicity in rats

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