Antineoplasic Drug Research Articles

Hybrid Gold Nanorod-Based Nanoplatform with Chemo and Photothermal Activities for Bimodal Cancer Therapy.

Metal nanoparticles (NPs), particularly gold nanorods (AuNRs), appear as excellent platforms not only to transport and deliver bioactive cargoes but also to provide additional therapeutic responses for diseased cells and tissues and/or to complement the action of the carried molecules. In this manner, here, we optimized a previous developed metal-based nanoplatform composed of an AuNR core surrounded by a polymeric shell constructed by means of the layer-by-layer approach, and in which very large amounts of the antineoplasic drug doxorubicin (DOXO) in a single loading step and targeting capability thanks to an outer hyaluronic acid layer were incorporated by means of an optimized fabrication process (PSS/DOXO/PLL/HA-coated AuNRs). The platform retained its nanometer size with a negative surface charge and was colloidally stable in a range of physiological conditions, in which only in some of them some particle clustering was noted with no precipitation. In addition, the dual stimuli-responsiveness of the designed nanoplatform to both endogenous proteases and external applied light stimuli allows to perfectly manipulate the chemodrug release rates and profiles to achieve suitable pharmacodynamics. It was observed that the inherent active targeting abilities of the nanoplatfom allow the achievement of specific cell toxicity in tumoral cervical HeLa cells, whilst healthy ones such as 3T3-Balb fibroblast remain safe and alive in agreement with the detected levels of internalization in each cell line. In addition, the bimodal action of simultaneous chemo- and photothermal bioactivity provided by the platform largely enhances the therapeutic outcomes. Finally, it was observed that our PSS/DOXO/PLL/HA-coated AuNRs induced cell mortality mainly through apoptosis in HeLa cells even in the presence of NIR light irradiation, which agrees with the idea of the chemo-activity of DOXO predominating over the photothermal effect to induce cell death, favoring an apoptotic pathway over necrosis for cell death.

Stability of a high-concentrated aqueous solution of idarubicin stored in a polypropylene syringe for transarterial chemoembolization

Idarubicin (IDA) is an antineoplasic drug commonly used to treat hematologic diseases. Because of its relative lipophilic properties, this anthracycline is also used in transarterial chemoembolization (TACE) as part of hepatocellular carcinoma (HCC) treatment. But TACE requires injected volume to be reduced to restrict systemic diffusion and side effects. The aim of this study was to determine the stability of a highly concentrated aqueous solution of IDA, stored in polypropylene syringes between 2 °C and 8 °C. Analyses were performed with an HPLC system combined with UV detector and mass spectrometer. Forced degradation was used to investigate potential degradation products. This study demonstrated 7 days of stability after storage in previously mentioned conditions. This conservation is long enough to anticipate drug preparation and facilitates pharmacy organization.

Pluronic F127/carfilzomib-based nanomicelles as promising nanocarriers: synthesis, characterization, biological, and in silico evaluations

In this work, we designed a drug delivery nanosystem based on oil-in-water Pluronic F127 nanomicelles to encapsulate and control the release of the antineoplasic drug carfilzomib (CFZ), and hypothesized that CFZ entrapment might result in a better effective and more localized cytotoxic effect on cancerous cells and to reduce its undesirable side effects for in vitro and in vivo applications. Pluronic F127/CFZ nanomicelles showed a high drug encapsulation efficiency (74.8%) and were allowed to achieve a sustained release pattern. Computational analyses were conducted to increase understanding of the nature and strength of mutual interactions between Pluronic F127 and CFZ. Simulation data indicated that the position of heteroatoms on CFZ influences the strength of attractive interactions in the Pluronic F127/CFZ nanomicelles. Cytotoxic activity of free and encapsulated CFZ was assayed in several cancerous cell lines, SHY-SY5Y human neuroblastoma, MCF7 breast, and HeLa cervical cancer cells employing the MTT colorimetric assay. We found that Pluronic F127/CFZ nanomicelles exhibited greater anti-proliferative activity than free CFZ (lower IC50s) and induced evident morphological alterations in cancer cells. Caspase-3 activity was assessed to determine the main mechanism of drug-induced cell death. Compared to free CFZ, our formulation only increased caspase-3 activity in HeLa cells. To examine the short-term toxicity of F127/CFZ nanomicelles, intravenous injections of free CFZ and F127/CFZ nanomicelles at three doses of 0.25 mg/kg, 0.5 mg/kg, and 1 mg/kg for five consecutive days were administered to an animal model. The potential anti-bactericidal activity of this new formulation was also assayed against four standard bacteria, including Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis. Unfortunately, no significant bacteria-killing effects were detected despite other drugs of the same family showing promising results. Still, our new formulation showed desirable anti-cancer effects and might be a good therapeutic modality for cancer treatment.

Characterization of imatinib mesylate formulations distributed in South American countries: Determination of genotoxic impurities by UHPLC-MS/MS and dissolution profile.

Imatinib mesylate (IM) is an anti-neoplasic drug used for the treatment of cancer. Recent new guidelines specify daily doses and concentration limits for genotoxic impurities (GTIs) in pharmaceutical final products. Therefore, in this work an analytical method using UHPLC-MS/MS was developed, validated and applied to characterize IM tablets for two GTIs: N-(2-methyl-5-aminophenyl)-4-(3-pyridyl)-2-pyrimidine amine (Imp. 1), and N-[4-methyl-3-(4-methyl-3-yl-pyrimidin-2-ylamino)-phenyl]-4- chloromethyl benzamide (Imp. 2), simultaneously. Additionally, dissolution data of IM tablets were compared using a methodology recommended by the US Food and Drug Administration. The UHPLC method utilized an Acquity BEH C18 (150 × 2.1 mm, 1.7 μm) maintained at 40°C. The mobile phase consisted of ammonium formate 0.063% (phase A) and acetonitrile plus 0.05% formic acid (phase B) in gradient elution. A sensitive method for determination of previously mentioned GTIs in IM tablets was successfully developed and applied. Overall, the formulations analyzed in this work showed low levels of Imp. 1 and Imp. 2. However, the sample named D1 showed very high levels of Imp. 1 and failed to meet the requirements established by the US Food and Drug Administration for dissolution data. Periodic verification of GTIs in pharmaceutical formulations is important to minimize safety risks, so analytical methods to determine it need be available and implemented in routine analysis.

Preparation of a Mini-Library of Thermo-Responsive Star (NVCL/NVP-VAc) Polymers with Tailored Properties Using a Hexafunctional Xanthate RAFT Agent.

A mini-library of star-shaped thermoresponsive polymers having six arms was prepared using a hexafunctional xanthate by reversible addition–fragmentation chain transfer (RAFT) polymerization. Star polymers with homopolymeric arms of poly(N-vinylcaprolactam) (PNVCL), copolymeric arms of poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) (PNVCL-co-PNVP) and also arms of block copolymers of PNVCL-b-PVAc, (PNVCL-co-PNVP)-b-PVAc, and combinations of them changing the order of the block was achieved exploiting the R-RAFT synthetic methodology (or R-group approach), wherein the thiocarbonyl group is transferred to the polymeric chain end. Taking advantage of the RAFT benefits, the molecular weight of the star polymers was controlled (Mn = 11,880–153,400 g/mol) to yield star polymers of different sizes and lower critical solution temperature (LCST) values. Removing the xanthate group of the star polymers allowed for the introduction of specific functional groups at the ends of the star arms and resulted in an increase of the LCST values. Star PNVCL-b-PVAc diblock copolymers with PVAc contents of 5–26 mol % were prepared; the hydrophobic segment (PVAc) is located at the end of the star arms. Interestingly, when the PVAc content was 5–7 mol %, the hydrodynamic diameter (Dh) value of the aggregates formed in water was almost the same sa the Dh of the corresponding PNVCL star homopolymers. It is proposed that these star block copolymers self-assemble into single flowerlike micelles, showing great stability in aqueous solution. Star block copolymers with the PVAc hydrophobic block in the core of the star, such as PVAc-b-(PNVCL-co-PNVP), form micellar aggregates in aqueous solution with Dh values in the range from ~115 to 245 nm while maintaining a thermoresponsive behavior. Micellar aggregates of selected star polymers were used to encapsulate methotrexate (MTX) showing their potential in the temperature controlled release of this antineoplasic drug. The importance of the order in which each block constituent is introduced in the arms of the star polymers for their solution/aggregation behavior is demonstrated.

Genotoxic potential of Jacareubein; a possible antineoplasic drug

Genotoxic potential of Jacareubein; a possible antineoplasic drug

OBTENCIÓN DE UNA FRACCIÓN ANTIMITÓTICA DEL EXTRACTO ETANÓLICO DE LA MACROALGA DIGENIA SIMPLEX

Marine algae have been widely studied by natural products chemists in the search of antitumor agents and the development of new therapeutic agents against cancer. Extracts of the red alga Digenia simplex display a powerful antimitotic effect in cancer cell lines. Therefore, it is of extreme importance to determine what substances are responsible of this activity. In order to achieve this objective, the ethanol extract of Digenia simplex was subject to chromatographic fractionation guided by evaluation of antimitotic activity on the Jurkat cell line (human myeloid lymphoma). Additionally, the most active fraction obtained was tested for cytotoxicity. Normal phase column chromatography and preparatory thin layer chromatography were used for extract fractionation. Cytotoxicity was assessed by cellular viability methods, determining cellular viability by the exclusion of the vital dye trypan blue. A cytotoxic and antimitotic fraction of polar nature was obtained. This fraction behaved in a similar way to the antineoplasic drug Colcemid.

Production of biodegradable porous scaffolds impregnated with 5-fluorouracil in supercritical CO2

Supercritical fluid technology was tested to produce biodegradable porous probes impregnated with an antineoplasic drug that once conformed could be used as scaffolds as an alternative to traditional methods of preparation. The impregnation of 5-fluorouracil, a chemotherapy agent, was carried-out at the same time to the foaming process in a one-shot procedure. The polymer foam probes were based on d,l-lactide and glycolide and prepared varying the operating conditions. The homopolymer poly(d,l-lactide) and the copolymer poly(d,l-lactide-co-glycolide) were used as base materials. The influence of stirring speed and venting rate on the drug loading and the average pore size were evaluated in order to optimize the impregnation process.Venting rate revealed to be the most important factor affecting the probes pore size and their morphology. Slow venting rates should be used to promote small pores in order to retard the drug release from the polymeric matrix. Fast stirring rates improves the impregnation process because favours the contact between supercritical CO2 and the swelled polymer. The presence of glycolide enhanced the mechanical strength of the foam preventing pore collapse. This fact together with the possibility of regulating the rate of the scaffold degradation and the kinetics of drug release makes the usage of the copolymer more attractive for a further medical application.

Toxoplasma gondii invasion and replication within neonate mouse astrocytes and changes in apoptosis related molecules

Toxoplasma gondii invades any nucleated cell, but different replication speed and effects on survival/apoptosis processes have been found depending on cell type. There are scarce and controversial results regarding the effect of this parasite on host cell apoptosis within the brain. The invasion and replication of T. gondii RH strain within newborn mouse astrocytes were evaluated in the present work. At 4 hpi>90% cells were infected and harbored one to three parasitophorous vacuoles with one tazchyzoite/vacuole. Cell culture massive destruction started after 24 h of exposure, when the parasite already replicated, with a duplication time of around 5 h. The effect of T. gondii infection on apoptosis was also evaluated by changes in some anti- and pro-apoptotic markers. At early infection times decreased Bcl-2, Survivin and PUMA and increased Noxa expression was found, although Survivin and Noxa mRNA levels reverted towards an anti-apoptotic phenotype after 6 h. Caspases 3/7 activity decreased three hours after infection, although it returned to normal levels thereafter. This enzymatic activity was strongly stimulated by Cisplatin (anti-neoplasic drug) but it was inhibited by previous T. gondii infection. Likewise, parasite invasion prevented PARP-1 fragmentation and cell apoptosis induced by the same drug. In conclusion, astrocytes seem to activate some apoptosis signals shortly after infection, but the parasite takes control of the cell and inhibits programmed death for up to 24 h, until it replicates, egresses and generates cellular destruction.

The bradykinin B1 receptor antagonist R-954 inhibits Ehrlich tumor growth in rodents

The present study investigated the effects of a new bradykinin B1 receptor antagonist, R-954, on the development of Ehrlich ascitic tumor (EAT) induced by the intraperitoneal inoculation of EAT cells in mice and the formation of a solid tumor by the subcutaneous injection of the cells in rat paw. The development of the tumor was associated with an increase in mouse total cell counts in bone marrow (10.8-fold), ascitic fluid (14.6-fold), and blood (12.6-fold). R-954 (2mg/kg, s.c.) significantly reduced the ascitic fluid volume (63.7%) and the mouse weight gain (30.5%) after 10 consecutive days of treatment. The B1 antagonist as well as the anti-neoplasic drug vincristine also significantly inhibited the increase in total cell count in bone marrow, ascitic fluid, and blood. R-954 reduced significantly the total protein extravasation (57.3%), the production of nitric oxide (56%), PGE2 production (82%), and TNFα release (85.7%) in mice peritoneal cavity whereas vincristine reduced the release of these inflammatory mediators by 84–94%. The increase in paw edema after intraplantar injection of EAT cells was reduced by approximately 52% by either R-954 or vincristine treatment. In conclusion, this study presents for the first time the antitumoral activity of a new bradykinin B1 receptor antagonist on ascitic and solid tumors induced by Ehrlich cell inoculation in mice and rats.

Recent Insights on the Medicinal Chemistry of Sickle Cell Disease

Sickle Cell Disease (SCD) is one of the most prevalent hematological diseases in the world. SCD is a genetic disease characterized by punctual mutation that basis on the exchange of glutamic acid to valine in a beta chain of hemoglobin. In deoxygenated state, the interaction among the beta chains leads to hemoglobin polymerization carrying out to deformation of cytoskeleton structure of red blood cells to a sickle shape. Currently, the treatment is performed with the antineoplasic drug hydroxyurea. This review summarizes current knowledge about possible targets and the approaches to discover new compounds to treat the SCD symptoms. Drug design based on therapeutical application and molecular modifications strategies will be discussed.

5‐Fluorouracil and its active metabolite FdUMP cause DNA damage in human SW620 colon adenocarcinoma cell line

5-Fluorouracil (5-FU) is an antineoplasic drug widely used to treat cancer. Its cytotoxic effect has been principally ascribed to the misincorporation of fluoronucleotides into DNA and RNA during their synthesis, and the inhibition of thymidylate synthase (TS) by FdUMP (one of the 5-FU active metabolites), which leads to nucleotide pool imbalance. In the present study, we compared the ability of 5-FU and FdUMP to induce apoptosis and to influence the cell cycle progression in human colon SW620 adenocarcinoma cells in regards to their genotoxic and clastogenic activities. Our study demonstrates that 5-FU induces SSB, DSB and apoptosis earlier than FdUMP. Interestingly, while both drugs are able to induce apoptosis, their effect on the cell cycle progression differed. Indeed, 5-FU induces an arrest in G1/S while FdUMP causes an arrest in G2/M. Independently of the temporal difference in strand breaks and apoptosis induction, as well as the differential cell cycle modulation, both drugs presented similar clastogenic effects. The different pattern of cell cycle arrest suggests that the two drugs induce different types of primary DNA lesions that could lead to the activation of different checkpoints and recruit different DNA repair pathways.

Serotonin 5-HT2A receptor involvement and Fos expression at the spinal level in vincristine-induced neuropathy in the rat

We recently showed that peripheral and spinal 5-HT2A receptors (5-HT2AR) are involved in a rodent model of neuropathy induced by a nucleoside analogue reverse transcriptase inhibitor. In this paper, we show that 5-HT2AR are also involved in neuropathy induced by an anti-neoplasic drug, vincristine. Vincristine-treated rats (0.1 mg/kg, daily i.p. administration for two 5-day cycles) developed thermal allodynia and mechanical hypersensitivity, which decreased in a dose-related manner after epidural injection a 5-HT2A receptor antagonist. Moreover, 5-HT2A−/− mice did not develop vincristine-induced neuropathy contrarily to their 5-HT2A+/+ littermates. In vincristine-treated rats, the number of nociceptive dorsal root ganglion cells expressing the 5-HT2AR was increased by 38%, and 5-HT2AR immunolabelling was enhanced in layers I–IV of the dorsal horn. At the EM level, a 76.3% increase in the density of 5-HT2AR immunopositive axon terminals within superficial layers of the dorsal horn was noted after vincristine treatment. Immunocytochemical study of Fos expression in vincristine-treated rats revealed a significant increase in the number of Fos-positive neurons not only in regions where nociceptive fibres terminate superficial (I–II) and deep layers (V–VI) of the spinal cord, but also in intermediate layers, suggesting that Aβ fibres could be involved in the spinal sensitization observed in this model. Double labelling experiments showed that Fos-positive neurons were endowed with 5-HT2AR immunolabelling in the dorsal horn of vincristine-treated rats. These data provide support to the idea that, in vincristine-induced neuropathy, 5-HT2AR are involved in the sensitization of peripheral nociceptors and spinal nociceptive processing.

Ceramides and Sphingomyelins with High Proportions of Very Long-chain Polyunsaturated Fatty acids in Mammalian Germ Cells

Very long-chain polyunsaturated fatty acids (VLCPUFA) have previously been shown to be components of sphingomyelin (SM) of mammalian testis and spermatozoa. Here we examined the fatty acids of testicular ceramide (Cer) in comparison with those of SM in some mammals with a special focus on the rat testis. In bull, cat, dog, rabbit, mouse, and rat, VLCPUFA were found in both testicular lipids, Cer having a higher percentage of VLCPUFA than SM. Rat testis had the highest percentage of VLCPUFA in both lipids, the major ones being 28:4n-6 and 30:5n-6. VLCPUFA-containing SM and Cer occurred in cells located in the seminiferous tubules, where germ cells had a higher percentage of these species than Sertoli cells. Seminiferous tubule fractionation showed that SM and Cer of mitochondria and lysosomes had mostly saturates and negligible VLCPUFA, the latter being important in the SM and Cer of microsomes and other membrane fractions. VLCPUFA were absent from the SM and Cer of rat prepuberal testis, increased with the onset of spermatogenesis to account for nearly 15 and 40% of the total fatty acids of testicular SM and Cer, respectively, remained at those levels throughout the adult life of fertile rats and tended to decrease at advanced ages. Four conditions that lead to selective death of germ cells in vivo, namely experimental cryptorchidism, post-ischemic reperfusion, focalized x-ray irradiation and treatments with the antineoplasic drug doxorubicin, caused the VLCPUFA to disappear from the testicular SM and Cer of adult fertile rats, showing that these lipids are specific traits of spermatogenic cells.

Efeito da mitomicina C em polipose nasossinusal eosinofílica, in vivo: dosagem de IL5 e GM-CSF, RT-PCR

A polipose nasossinusal eosinofílica (PNS) é manifestação de uma doença inflamatória crônica na mucosa do nariz e nos seios paranasais caracterizada por infiltração de granulócitos eosinófilos. O fator responsável pela eosinofilia e manutenção dessas células com a perpetuação do processo inflamatório e formação polipóide é objeto constante de estudos. As citocinas como IL5 (interleucina 5) e GM-CSF (fator estimulador de colônia granulócito macrófago) aumentam a sobrevida dos eosinófilos e prolongam a sua presença no tecido polipóide, diminuindo o índice de apoptose eosinofílica. OBJETIVO: Avaliar o efeito da mitomicina C - MMC - por meio de aplicação tópica em pacientes portadores de PNS eosinofílica quanto à presença de IL5 e GM-CSF. CASUÍSTICA E MÉTODOS: Quinze pacientes portadores de PNS eosinofílica foram submetidos à aplicação tópica de MMC na concentração de 0,5mg/ml, 1ml, durante cinco minutos, na cavidade nasal direita, e submetidos à biópsia para RT-PCR 24hs após. O grupo-controle foi a cavidade nasal esquerda. O perfil de citocinas foi analisado para IL5 e GM-CSF. RESULTADOS: A comparação dos resultados de GM-CSF pré e pós-uso de MMC quando usamos o teste t pareado apresenta p=0,041. A comparação para IL5 resulta em p < 0,001. CONCLUSÃO: O uso de MMC em pacientes com PNS mostra redução com significância estatística par GM-CSF e importante significância para IL5.

Are the Antioxidant Properties of Carvedilol Important for the Protection of Cardiac Mitochondria?

The cellular role of mitochondria includes ATP generation and the modulation of cytosolic calcium signals, besides being the "crossroads" for several cell death pathways. The maintenance of optimal mitochondrial functioning during the disease process increases the chances for survival. For example, ischaemia followed by reperfusion is known to negatively affect mitochondrial function, namely by inducing a deleterious condition called mitochondrial permeability transition (MPT). The MPT is responsible for mitochondrial dysfunction and can ultimately lead to cell death. Therefore, it seems important to protect mitochondrial function in cardiac disease. Carvedilol, a beta-adrenergic receptor antagonist with antioxidant properties, has a positive impact on cardiac mitochondria during in vitro, ex-vivo and in vivo models of cardiac dysfunction. Particularly, carvedilol was shown to inhibit MPT in isolated heart mitochondria and protect mitochondria against the oxidative damage induced by the xanthine oxidase/hypoxanthine pro-oxidant system. The observation that carvedilol acts as an inhibitor of mitochondrial complex-I is also of importance, since this mitochondrial system was proposed as cause of the cardiotoxicity associated with the anti-neoplasic drug doxorubicin. This review points out the major findings concerning the positive impact of carvedilol on mitochondrial function and its use in the treatment of myocardial diseases where oxidative stress is known to be involved.

Evidence for an antihyperalgesic effect of venlafaxine in vincristine-induced neuropathy in rat

Venlafaxine, a new antidepressant with fewer side effects, could be of interest to reduce neuropathic pain following antineoplasic drug treatment. In the present study, we demonstrated that venlafaxine inhibits hyperalgesia in a new rat model of neuropathy induced by the antineoplasic drug vincristine, and exerts its effect preferentially via supraspinal and spinal mechanisms.

Monitoramento da audição de pacientes expostos à cisplatina

A cisplatina é um agente quimioterápico que apresenta dentre seus efeitos colaterais a ototoxicidade. Este estudo teve como objetivos avaliar a audição de pacientes portadores de osteossarcoma expostos à cisplatina e verificar qual o método de investigação mais adequado para identificar precocemente as alterações auditivas induzidas por drogas ototóxicas. FORMA DE ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: 13 indivíduos portadores de osteossarcoma que receberam quatro ciclos de cisplatina de 120 mg/m²/ciclo, fracionados em dois dias de aplicação (60 mg/m²/dia), foram submetidos à avaliação audiológica - audiometria tonal liminar (250 a 18000 Hz) e emissões otoacústicas transitórias (EOAT) e por produto de distorção (EOAPD) - antes do início do tratamento e após cada ciclo de cisplatina. RESULTADOS: Observou-se, nos valores médios, perda auditiva após a dose cumulativa de 480 mg/m² a partir de 8 kHz. Quanto aos valores individuais, 15,3% dos pacientes apresentaram perda auditiva de grau leve a moderado a partir de 3 kHz, 15,3% a partir de 4 kHz, 15,3% a partir de 6 kHz e 15,3% a partir de 8 kHz. Não foi observada redução na amplitude das EOAT precocemente à alteração dos limiares nas altas freqüências. Houve redução da amplitude das EOAPD concomitante ao aumento do limiar de audibilidade. CONCLUSÃO: A audiometria de altas freqüências é mais efetiva na detecção precoce da perda auditiva induzida por cisplatina. As EOAT e EOAPD podem ser usadas como complemento à avaliação audiométrica. Todos os pacientes expostos à cisplatina têm perda auditiva nas altas freqüências, e destes, 30,6% tem perda auditiva a partir das freqüências de 3 e 4 kHz consideradas importantes para a compreensão da fala.

Electrochemical detection of in situ adriamycin oxidative damage to DNA

Adriamycin intercalation and in situ interaction with double helix DNA was investigated using a voltammetric DNA-biosensor. Oxidation and reduction of adriamycin molecules intercalated in double helix DNA were investigated in order to understand the in vivo mechanism of action with this anti-neoplasic drug. The results showed that the interaction of adriamycin with DNA is potential-dependent causing contact between DNA guanine and adenine bases and the electrode surface such that their oxidation is easily detected. A mechanism for adriamycin reduction and oxidation in situ when intercalated in double helix DNA immobilised onto the glassy carbon electrode surface is presented and the formation of the mutagenic 8-oxoguanine explained.

Effect of oral selenium administration on cisplatin-induced nephrotoxicity in rats

Cis -diamminedichloroplatinum(II) (CP), an important antineoplasic drug, shows remarkable toxicity to the kidney. Methods to reduce CP nephrotoxicity include the use of sodium selenite. The aim of the present study was to investigate the interaction between orally administered selenium and CP in the rat. After observing the effects of CP on body growth rate, urinary volume, serum creatinine, serum selenium levels, creatinine clearance, renal malondialdehyde, and glutathione levels, as well as on renal light microscopically visible lesions, the effects of the sodium selenite administration by gavage of 2 mg per kg of body wt. 24 h and 1 h prior to a single CP intraperitoneal injection of 5 mg per kg of body wt. followed by its daily administration for the 7 subsequent days on these parameters, were examined. CP increased renal malondialdehyde, renal glutathione, and serum creatinine and decreased creatinine clearance. Lipid peroxidation is one of the mechanisms by which CP induces renal damage. Selenium treatment decreased the effect of CP on serum creatinine, and renal malondialdehyde levels, but did not affect the other parameters with the exception of kidney necrosis which was also diminished by this treatment.