Time dependent protection of amifostine from renal and hematopoietic cisplatin induced toxicity

Asna, Noam; Lewy, Hadas; Ashkenazi, Israel; Deutsch, Varda; Peretz, H.; Inbar, Moshe; Ron, Idit

doi:10.1016/j.lfs.2004.09.028

Cited by 31 publications

(15 citation statements)

References 18 publications

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“…Similarly, several workers have described CISPLAT-induced decreased/depleted numbers of cells in the marrow, in the mouse (Zak et al 1972;Nowrousian and Schmidt 1982), rat (Thompson and Gale 1971;Ward and Fauvie 1976) and in the dog and monkey (Schaeppi et al 1973). In the peripheral blood of CISPLAT-treated mice, there are descriptions of anaemia (reduced RBC/Hb/HCT values), decreased platelets and WBC, neutrophils and lymphocytes (Zak et al 1972;Nowrousian and Schmidt 1982;Schurig et al, 1973;Asna et al 2005). In the rat, Wood and Hrushesky (1995) and Badary et al (2005) reported anaemia.…”

Section: Discussionmentioning

confidence: 99%

Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration

et al. 2010

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Many anticancer drugs are myelotoxic and cause bone marrow depression; however, generally, the marrow/blood returns to normal after treatment. Nevertheless, after the administration of some anti-neoplastic agents (e.g. busulphan, BU) under conditions as yet undefined, the marrow may begin a return towards normal, but normality may not be achieved, and late-stage/residual marrow injury may be evident. The present studies were conducted to develop a short-term mouse model (a 'screen') to identify late-stage/residual marrow injury using a brief regimen of drug administration. Female BALB/c mice were treated with BU, doxorubicin (DOX), cisplatin (CISPLAT) or cyclophosphamide (CYCLOPHOS) on days 1, 3 and 5. In 'preliminary studies', a maximum tolerated dose (MTD) for each drug was determined for use in 'main studies'. In main studies, mice were treated with vehicle (control), low and high (the MTD) dose levels of each agent. Necropsies were performed, and blood parameters and femoral/humeral nucleated marrow cell counts (FNCC/HNCC) were assessed on six occasions (from days 1 to 60/61 post-dosing). Late-stage/residual changes were apparent in BU-treated mice at day 61 post-dosing: RBC, Hb and haematocrit were reduced, mean cell volume/mean cell haemoglobin were increased and platelet and FNCC counts were decreased. Mice given DOX, CISPLAT and CYCLOPHOS, in general, showed no clear late-stage/residual effects (day 60/61). It was concluded that a brief regimen of drug administration, at an MTD, with assessment at day 60/61 post-dosing was a suitable short-term method/screen in the mouse for detecting late-stage/residual marrow injury for BU, a drug shown to exhibit these effects in man.

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Section: Discussionmentioning

confidence: 99%

Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration

et al. 2010

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“…It is known to act via a mechanism that involves the scavenging of free radicals, the donation of hydrogen ions to free radicals, the depletion of oxygen, and the binding to active derivatives of antineoplastic agents. 14,15) Thus, as a part of our on-going screening program to evaluate the protective potentials of natural compounds, we investigated the nephroprotective activity of the ethanol extract of the roots of Brassica rapa in vitro and in vivo. The group Brassica rapa includes many significant crops such as the Chinese cabbage; in Italy this group is mainly represented by turnip tops [B. rapa L. subsp.…”

mentioning

confidence: 99%

Protective Effect of the Ethanol Extract of the Roots of Brassica rapa on Cisplatin-Induced Nephrotoxicity in LLC-PK1 Cells and Rats

Kim

et al. 2006

Biological & Pharmaceutical Bulletin

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Cisplatin (cis-diaminedichloroplatinum II) is one of the most effective chemotherapeutic agents and plays a major role in the treatment of a variety of human solid tumors including those of the head, neck, testis, ovary, and breast. 1)However, the nephrotoxicity of cisplatin limits the efficacy of this important anticancer drug.2) Although the pathogenesis of cisplatin-induced acute renal failure (ARF) has been the subject of many studies, the molecular mechanisms that underlie its toxicity are poorly understood. Some investigators have suggested that free radicals play an important role in cisplatin-induced nephrotoxicity, 3,4) and another proposed that reactive oxygen species (ROS), particularly the superoxide radical, play an important role in cisplatin-induced renal injury.5) It has also been reported that cisplatin-induced nephrotoxicity is closely associated with an increase in lipid peroxidation in the kidney. 6,7) In addition, cisplatin has been found to inhibit antioxidant activity 8) and to induce GSH depletion, which has been proposed to be involved in nephrotoxicity.9,10) Some evidence suggests that free radical scavengers and antioxidants ameliorate cisplatin-induced nephrotoxicity.11) The antioxidant DPPD (N,NЈ-diphenyl-pphenylenediamine) reduced nephrotoxicity in cisplatintreated rats, inhibited an increase in lipid peroxide level, and reduced the inhibition of p-aminohippurate transport in vitro.12,13) Actually, amifostine has been clinically approved as a cytoprotective agent during cisplatin therapy. It is known to act via a mechanism that involves the scavenging of free radicals, the donation of hydrogen ions to free radicals, the depletion of oxygen, and the binding to active derivatives of antineoplastic agents.14,15) Thus, as a part of our on-going screening program to evaluate the protective potentials of natural compounds, we investigated the nephroprotective activity of the ethanol extract of the roots of Brassica rapa in vitro and in vivo. The group Brassica rapa includes many significant crops such as the Chinese cabbage; in Italy this group is mainly represented by turnip tops [B. rapa L. subsp. sylVestris (L.) JANCH var. esculenta HORT.], which are used as a cooked vegetable and are known as "cime di rapa." In Korea, Brassica rapa is cultivated commercially in GangHwa County, Kyunggi Province. In previous studies on Brassica rapa, flavonoids (isorhamnetin, kaempferol, and quercetin glycosides), 16) phenylpropanoid derivatives, 16) indole alkaloids, 17) and sterol glucosides 17) were identified. The only report on the minor components of B. rapa involved the determination of glucosinolates, a group of secondary metabolites of b-thioglucose, which is characteristics of the genus of Brassica.17) It is generally assumed that flavonoid components are of great importance in view of their biological effects of the human metabolism, 18) but no report has been issued on the protective effect of B. rapa on cisplatin-induced nephrotoxicity. Therefore, we investigated whether the ethanol extract...

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“…It is well known that the CDDP treatment induces a myelotoxicity through the alteration of the bone marrow, which was confirmed in the present study. 20,21 By contrast, no alteration in the renal tissue after the administration of all formulations containing CDDP, could be verified. These results are similar to those obtained from other studies, which demonstrated alterations in the hematological parameters and the absence of renal toxicity due to the repeated administration of a liposomal formulation containing CDDP in experimental models.…”

Section: Discussionmentioning

confidence: 93%

Encapsulation of cisplatin in long-circulating and pH-sensitive liposomes improves its antitumor effect and reduces acute toxicity

Leite¹,

Souza²,

Carvalho-Junior³

et al. 2012

IJN

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Cisplatin (CDDP) is one of the most effective and potent anticancer drugs used as first-line chemotherapy against several solid tumors. However, the severe side effects and its tendency to provoke chemoresistance often limit CDDP therapy. To avoid these inconveniences, the present study's research group developed long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP). The present study aimed to evaluate the antitumor effect and toxicity of SpHL-CDDP, as compared with that of free CDDP, and long-circulating and non-pH-sensitive liposomes containing CDDP (NSpHL-CDDP), after their intravenous administration in solid Ehrlich tumor-bearing mice. Antitumor activity was evaluated by analysis of tumor volume and growth inhibition ratio, serum vascular endothelial growth factor (VEGF) levels, and histomorphometric and immunohistochemical studies. Body weight variation and the histological examination of bone marrow and kidneys were used as toxicity indicators. A significant reduction in the tumor volume and a higher tumor growth inhibition ratio was observed after SpHL-CDDP treatment, compared with free CDDP and NSpHL-CDDP treatments. In addition, complete remission of the tumor was detected in 18.2% of the mice treated with SpHL-CDDP (16 mg/kg). As such, the administration of SpHL-CDDP, as compared with free CDDP and NSpHL-CDDP, led to a decrease in the area of necrosis and in the percentage of positive CDC 47 tumor cells. A significant reduction in the VEGF serum level was also observed after SpHL-CDDP treatment, as compared with free-CDDP treatment. SpHL-CDDP administered in a two-fold higher dose than that of free CDDP presented a loss in body weight and changes in the hematopoietic tissue morphology, which proved to be similar to that of free CDDP. No changes could be verified in the renal tissue after any formulations containing CDDP had been administered. These findings showed that SpHL-CDDP allowed for the administration of higher doses of CDDP, significantly improving its antitumor effect.

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Time dependent protection of amifostine from renal and hematopoietic cisplatin induced toxicity

Cited by 31 publications

References 18 publications

Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration

Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration

Protective Effect of the Ethanol Extract of the Roots of Brassica rapa on Cisplatin-Induced Nephrotoxicity in LLC-PK1 Cells and Rats

Encapsulation of cisplatin in long-circulating and pH-sensitive liposomes improves its antitumor effect and reduces acute toxicity

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