Effects of cis-Diamminedichloroplatinum II (Cisplatin) on the Splenic Tissue of Rats: A Histoquantitative Study

Milićević, Živana; Slepčević, Vesna; Nikolić, Dejan; Živanović, Vedran; Milićević, Novica M.

doi:10.1006/exmp.1994.1027

Cited by 11 publications

(7 citation statements)

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“…S7). Free CDDP treatment has previously been reported to have a remarkable effect on immunological function due to its ability to reduce lymphocytes in the thymus and the spleen with changes in splenic white pulp being the most significant [36]. Absence of (CDDP+PTX)/ cl -micelles in lymphoid regions of white pulp may thus limit free-drug exposure to these follicles.…”

Section: Resultsmentioning

confidence: 99%

Biodegradable hybrid polymer micelles for combination drug therapy in ovarian cancer

Desale

Cohen

Zhao

et al. 2013

Journal of Controlled Release

100

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Section: Resultsmentioning

confidence: 99%

Biodegradable hybrid polymer micelles for combination drug therapy in ovarian cancer

Desale

Cohen

Zhao

et al. 2013

Journal of Controlled Release

100

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“…We investigated the effects of three different cytostatic agents in rats by treating rats with a single dose of each cytostatic agent. We used a dose that was described to be proven effective [18] to obtain information regarding the shortand long-term effects of cytostatic agents on B cell populations [8,19,20].…”

Section: Discussionmentioning

confidence: 99%

“…Some shortterm effects in rats after a single dose of CP, MTX and CyPh have been reported. CP reduces specifically splenic follicles and the marginal zone in rats [8]; MTX can suppress both primary and secondary antibody responses [2,9]; CyPh causes lymphopenia of both T and B cells [2] and selective loss of lymphocytes from the marginal zone of the spleen [10].…”

Section: Introductionmentioning

confidence: 99%

Slow recovery of follicular B cells and marginal zone B cells after chemotherapy: implications for humoral immunity

Zandvoort¹,

Lodewijk²,

Klok³

et al. 2001

Clinical and Experimental Immunology

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SUMMARYAlthough most chemotherapeutic agents are known to cause primarily reduction or suppression of immune responses, surprisingly little is known about the influence of cytostatic agents on lymphoid tissue compartments such as the splenic marginal zone. The marginal zone plays an important role in the defence against encapsulated bacteria, which are potential candidates for postchemotherapeutic infections. We studied the effect of three different cytostatic agents (cisplatin, methotrexate, and cyclophosphamide) on B cell subpopulations in a rat model. Rats received a single dose of a single cytostatic agent and were sacrificed at different time points after treatment. Bone marrow, blood, mesenteric lymph nodes and spleens were analysed by flow-cytometry and immunohistochemistry. All three cytostatic agents showed severe bone marrow depression. CP and MTX showed only mild reduction of cell populations in the spleen. CyPh showed a severe reduction of recirculating follicular B (RF-B) cells and marginal zone B (MZ-B) cells. At day 24 most populations were already recovered, but RF-B cells and MZ-B cells were still reduced. The reduction of the marginal zone and late recovery may imply that, beside the overall increased infection risk due to neutropenia, patients treated with chemotherapy are at risk for developing infections from encapsulated bacteria for a considerable period of time after treatment, extending beyond the period of bone marrow depression.

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“…PS-exposing cells were rapidly cleared from circulation by reticuloendothelial system (RES), especially in spleen. However, there was little attention in previous studies paid to the subtle changes in the architecture of spleen as a lymphatic organ after cisplatin treatment [8]. Macrophages in the spleen play a major role in iron metabolism by recycling irons from erythrocytes.…”

Section: Introductionmentioning

confidence: 99%

Specific Hemosiderin Deposition in Spleen Induced by a Low Dose of Cisplatin: Altered Iron Metabolism and Its Implication as an Acute Hemosiderin Formation Model

Wang

et al. 2010

CDM

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Cisplatin is one of the commonly-used chemotherapeutic drugs to efficiently treat malignant tumors in clinic, however, the adverse effects of cisplatin such as nephrotoxicity, neurotoxcity, and hemolytic uremic syndrome are often observed at its clinical doses (~60 mg/m 2 ), which limit its broader application. In earlier studies, little attention was paid to the subtle changes in the architecture of lymphatic organs after low doses of cisplatin treatment. This paper reviews current understanding of cisplatin-induced erythrocyte injury, and presents our latest finding that a low dose of cisplatin (3.6 mg/m 2 /day, 14 days) could induce specific hemosiderin deposition in spleen of both normal and hepatoma-22 (H22) inoculated Balb/C mice. This dose of cisplatin significantly inhibited H22-induced acute ascites development. No significant toxicity was induced by this dose of cisplatin to tissues except for hemosiderin accumulation in the spleen of both normal and H22 tumor-bearing mice. Increased splenic iron content and erythrocyte injury were observed after treatment with the low dose of cisplatin. The mRNA levels of ferroportin (FPN1) and ferritin were upregulated by 25 and 5-fold in spleen, respectively. Overexpression of FPN1 and ferritin protein were also been observed at protein levels by Western blotting analysis. In addition, the mRNA expression of hepcidin was also increased, suggesting blockage of iron recycling through FPN1 in spleen with cisplatin treatment. In conclusion, cisplatin treatment damages the erythrocytes which accumulate in the red pulp of spleen with defective recycling of FPN1 and ferritin protein. Hepcidin inhibits the function of FPN1 as iron-exporter leading to iron overloaded inside ferritins of splenic cells, which are stained with abnormal hemosiderin accumulation. These results demonstrate that cisplatin-caused hemosiderin deposition in spleen provides a valuable clue for understanding the molecular basis of toxicity of cisplatin and hemosiderin accumulation and iron metabolism in vivo.

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Effects of cis-Diamminedichloroplatinum II (Cisplatin) on the Splenic Tissue of Rats: A Histoquantitative Study

Cited by 11 publications

References 0 publications

Biodegradable hybrid polymer micelles for combination drug therapy in ovarian cancer

Biodegradable hybrid polymer micelles for combination drug therapy in ovarian cancer

Slow recovery of follicular B cells and marginal zone B cells after chemotherapy: implications for humoral immunity

Specific Hemosiderin Deposition in Spleen Induced by a Low Dose of Cisplatin: Altered Iron Metabolism and Its Implication as an Acute Hemosiderin Formation Model

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