• Title/Summary/Keyword: Immunosuppressant

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Effects of Cyclophosphamide on Immunological Memory in Mice (Cyclophosphamide가 마우스의 면역기억에 미치는 영향)

  • Park, Young-Min;Park, Yoon-Kyu;Ahn, Woo-Sup;Ha, Tai-You
    • The Journal of the Korean Society for Microbiology
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    • v.22 no.2
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    • pp.175-184
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    • 1987
  • The use of alkylating agent cyclophosphamide(CY), a widely used antitumor drug is well known as a potent immunosuppressant and has been used as a probe for investigating the functional capabilities of lymphocyte subsets of both T and B cells that play an important role in the regulation of the immune response. The present study was undertaken in an effort to assess the effects of CY on immunological memory in murine model. CY, given as a single dose of CY(250mg/kg) before sensitization with sheep red blood cells(SRBC) enhanced the primary response of Arthus and delayed-type hypersensitivity(DTH), as measured by footpad swelling reaction, but suppressed their tertiary DTH response. The similar CY pretreatment enhanced both the primary and tertiary hemagglutinin(HA) responses to SRBC, and the tertiary antibody response against polyvinylpyrroridone(PVP), a thymus-independent antigen but not the primary response against PVP. CY, given as a single dose of 250mg/kg 2 days before the primary immunization and two doses of 100mg/kg 2 days before the secondary and tertiary immunization, markedly suppressed the tertiary DTH and HA responses to SRBC. However, CY, given as small multiple daily doses(10mg/kg) over 4 days before sensitization but not after sensitization, enhanced the secondary HA response to SRBC. Contact sensitivity to dinitrofluorobenzene(DNFB) was suppressed by the drug, given either as a single large dose(300mg/kg) or as multiple dose(10mg/kg) administered 2 days before, together with or after DNFB sensitization. This suppression was more pronounced and more significant when CY was given as multiple dose. However, the enhancement of the secondary contact sensitivity to DNFB by CY was not clear-cut. The splenectomy appears to increase the enhancing effect of CY on contact sensitivity. These results suggest that CY selectively influences the immune response depending on the time of the drug administration relative to immunization and that the secondary or tertiary immune response involve memory cells with different susceptibilities to CY. Moreover, these results suggest that multiple low doses may sesectivley inhibit suppressor T cell proliferation involving DTH, HA or contact sensitivity without effecting helper T cells, but high doses presumably inhibit helper T cells and suppressor T cells with effecting B cells.

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The Effects of Samulsopungeum and Prednisolone on NC/Nga Atopic Mice (사물소풍음(四物消風飮)과 Prednisolone이 NC/Nga mice의 아토피 피부염에 미치는 영향)

  • Yun, Chae-Sung;Joo, Hyun-A;Hwang, Chung-Yeon
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.1
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    • pp.59-74
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    • 2010
  • Objectives : Atopic dermatitis(AD) is a chronic recurrent skin disease which usually developed in infancy or childhood. AD often repeat improvement and relapse. The cause of AD is so indefinite that many methods of therapies(moisturizer, steroid ointment, antihistamine, immunomodulator, immunosuppressant, herbal medicine, alternative medicine, etc.) are tried. Recently, a lot of studies were made. But there is no report about the effect of Samulsopungeum(SM) and Prednisolone(PN) on AD. So, author aimed to investigate the effects of SM and PN on AD of NC/Nga mice. Methods : Thirty two mice(8 Balb/c mice and 24 NC.Nga mice) were divided into four groups; Balb/c mice was normal group. NC/Nga mice were divide into three group : control, PN, SM group. AD was induced in the control, PN, SM group by spreading DNCB. Then normal saline, PN and SM were orally administered three times in a week for 8 weeks to the control, PN, SM group, respectively. We observed changes of clinical skin severity score, serum IgE, IgG1, IFN-$\gamma$, IL-2, IL-4, IL-5, IL-10, IL-13, and so on. We used one-way ANOVA test statistically(p<0.01). Results : The clinical skin severity scores of PN group and SM group in 8th week were decreased compared to the control group. Serum IgE, IgGl levels of PN group and SM group were significantly decreased compared to the control group. Serum IFN-$\gamma$ in SM group was significantly increased compared to the control group. But, Serum IFN-$\gamma$ in PN group was significantly decreased compared to the control group. Serum IL-10 levels of PN group and SM group were significantly decreased compared to the control group. Serum IL-2, IL-4, IL-5, IL-13 levels of PN group and SM group were significantly decreased compared to the control group. mRNA expression levels of IL-2, IL-4, IL-5, IL-13 in the dorsal skin tissues of PN group and SM group were significantly decreased compared to the control group. According to biopsy reports of the ear and skin tissues showed that the tissue damage of PN group and SM group were highly reduced compared to the control group. Creatinine, BUN, ALT, AST levels of PN group and SM group were normal. Conclusion : According to the above results, it is considered that SM is effective treatment for the AD.

Ulmus macrocarpa Hance Reduces Cyclophosphamide-induced Toxicity in Mouse Liver (Cyclophosphamide가 유발한 간 조직변화에 대한 느릅나무 열수추출물의 완화 효과)

  • Kim, Deok Won;Chung, Kyung Tae
    • Journal of Life Science
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    • v.31 no.2
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    • pp.223-228
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    • 2021
  • Cyclophosphamide (CP) is widely used in cancer and lymphoma treatments and as an immunosuppressant drug. CP is a DNA alkylating agent that metabolizes into 4-hydrocyclophosphamide (4H-CYP) and aldophosphamide in hepatocytes. However, its metabolites cause DNA synthesis disorder, leading to apoptosis and toxic side effects. The development of technology to minimize this side effect is essential to improve CP's clinical application. Various bioactive compounds have been reported to have anti-cancer and antioxidant functions and preventive or therapeutic roles in metabolic diseases. Many researchers have attempted to minimize the side effects and improve the efficacy of these drugs together with the use of bioactive compounds. Ulmus macrocarpa Hance has been used for the treatment of edema, mastitis, stomach pain, tumors, cystitis, and other inflammatory diseases. The aim of this study was to investigate at the histological level the protective function of U. macrocarpa Hance against CP's side effects and any potential toxic effect of U. macrocarpa Hance in the liver and kidney. Water extracts of U. macrocarpa Hance reduced CP-induced toxicity and did not induce any histological damage in the liver and kidney. Therefore, U. macrocarpa Hance would be applicable in the pharmaceutical industry.

Facial Paralysis and Myositis Following the H3N2 Influenza Vaccine in a Dog

  • Ju-Hyun An;Ye-In Oh;So-Hee Kim;Su-Min Park;Jeong-Hwa Lee;Ga-Hyun Lim;Kyung-Won Seo;Hwa-Young Youn
    • Journal of Veterinary Clinics
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    • v.40 no.5
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    • pp.336-340
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    • 2023
  • A dog (2-year old, female, Shih-Tzu) presented with hyperthermia and right-sided facial paralysis characterized by the inability to close the right eye and drooling from the right side of the mouth after H3N2 influenza vaccination [A/Canine/Korea/01/07(H3N2) strain; Caniflu-Max, Bionote, Hwaseong, Gyeonggi-do, ROK]. To determine the cause of the fever and neurological symptoms, physical examination, ophthalmic examination, thoracic and abdominal radiography, abdominal ultrasonography, complete blood counts, serum chemistry values, and electrolyte levels were determined. In addition, Cerebrospinal fluid analysis, antinuclear antibody test, fever of unknown origin polymerase chain reaction (PCR) panel, tick-borne pathogen PCR panel were performed. As a result, hyperthermia, leukocytosis, and elevated C-reactive protein were confirmed. In addition, neurological examination revealed decreased right eyelid reflexes, corneal reflexes, threat response, and facial sensation, it was possible to suspect problems with the trigeminal and facial nerves of the cranial nerve. Magnetic resonance imaging revealed a lesion suggestive of myositis in the right muscular lesion at atlanto-occipital junction level on site of vaccine injection. Therefore, right-sided facial paralysis was tentatively determined to be a secondary cause of nerve damage caused by myositis. The patient was treated with immunosuppressants such as prednisolone and mycophenolate mofetil. After 3 months of immunosuppressant therapy, the patient's symptoms improved.

Prodigiosin Production From Serratia sp. PDGS120915 Isolated From Daeyeon Stream Water in Busan (하천에서 분리한 Serratia sp. PDGS120915의 프로디지오신 생산)

  • Keunho Ji;Young Tae Kim
    • Journal of Life Science
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    • v.34 no.6
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    • pp.377-384
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    • 2024
  • Prodigiosin is a red pigment characterized by a common pyrrolylpyrromethane skeleton. It is produced by Serratia marcescens, Vibrio psychroerythrus, Hahella chejuensis, etc. Prodigiosin has been reported to possess anticancer, immunosuppressant, antifungal antimalarial, and algicidal activities. However, despite prodigiosin's diverse range of activities, its production rate is significantly low and biosynthesis conditions are difficult. Consequently, the selling price is high, and its usability is limited. This study aimed to increase the efficiency of prodigiosin production according to the culture conditions of Serratia. In this study, a bacterial strain PDGS120915 producing prodigiosin was isolated from lightly contaminated stream water in Busan and identified as a strain of Serratia sp. based on 16S rDNA gene sequence analysis and physiological characteristics. The reddish pigment from PDGS120915 was directly extracted using acidified ethanol, and a characterization analysis confirmed that it was a prodigiosin compound. The optimal conditions for pigment production were 25℃, pH 7, and 0% NaCl concentration for a duration of 14 hr. Furthermore, by treating carbon and nitrogen sources, such as fructose and beef extract, respectively, prodigiosin production increased approximately six-fold and four-fold. Among the minerals tested, 0.1% KCl was found to be the most effective for prodigiosin production. Moreover, casein was identified as the most suitable source for prodigiosin production.

Anti-inflammatory Activity of Crinum asiaticum Linne var. Japonicum Extract and its Application as a Cosmeceutical Ingredient (문주란의 항염효과와 화장료적 특성)

  • Kim, Ki-Ho;Kim, Young-Heui;Kim, Ki-Soo;Park, Sun-Hee;Lee, Soo-Hee;Kim, Young-Jin;Kim, Young-Sil;Kim, Jong-Heon
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.32 no.1 s.55
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    • pp.59-64
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    • 2006
  • Crinum asiaticum Linne var. japonicum has long been used as a rheumatic remedy, an anti-pyretic, an anti-ulcer treatment, and for the alleviation of local pain and fever in Korea and Malaysia. In order to investigate the possibility of Crinum asiaticum Linne var. japonicum extract as a cosmetic ingredient, we measured its anti-inflammatory effect by inhibition of iNOS (inducible nitric oxide synthase), and the release of PGE2, IL-6, and IL-8. HPLC experiment after extraction with 95% ethanol at pH 3.5 showed that Crinum asiaticum Linne var. japonicum was mainly composed of lycorine (up to 1%), a well-known immunosuppressant. The content of lycorine varied depending on the type of tissue analyzed and the extraction method. In anti-inflammatory assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)- activated mouse macrophage RAW 264.7 cells, the ethanolic extract of Crinum asiaticum showed inhibitory activity of NO production in dose-dependent manner ($IC_{50} = 83.5 {\mu}g/mL$). Additional study by RT-PCR demonstrated that the extract of Crinum asiaticum significantly suppressed the expression of the iNOS gene. Moreover, the extract of Crinum asiaticum did not show my cytotoxicity, but did show cell proliferation effect against LPS ($10{\sim}60%$ increase of tell viability). In an assay to determine inhibition of the $H_2O_2$-activated release of PGE2, IL-6, and IL-8 in human normal fibroblast cell lines, the release of PGE2 and IL-6 was almost completely inhibited above concentrations of 0.05% and 1%, respectively. Moreover, the release of IL-8 was completely inhibited over the entire range of concentrations (> 0.0025%). The result showed that the extract of Crinum asiaticum Linne var. japonicum has sufficient anti-inflammatory effect. There-fore, Crinum asiaticum Linne var. japonicum extract may be useful as an ingredient of cosmetic products.

Clinical Manifestation and Treatment Outcome of Lupus Nephritis in Children (소아 루프스 신염의 임상양상 및 치료결과)

  • Park Jee-Min;Shin Jae-Il;Kim Pyung-Kil;Lee Jae-Seung
    • Childhood Kidney Diseases
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    • v.6 no.2
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    • pp.155-168
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    • 2002
  • Purpose; Systemic lupus erythematosus(SLE) is an autoimmune disease with multi-system involvement and renal damage is a major cause of morbidity and mortality in children. Renal involvement is more common and severe in children than in adults. Therefore, renal biopsy plays a crucial role in planning effective therapy. In this study, we investigated the clinical and pathological findings of lupus nephritis in children to aid clinical care of the disease. Methods: The clinical and pathological data of 40 patients who were diagnosed as SLE with renal involvement in Shinchon Severance Hospital from Jan. 1990 to Sep. 2002 were analyzed retrospectively. Results: The ratio of male to female patients was 1:3 and the median age at diagnosis was 12.1(2-18) years old. FANA(95.0%), anti-ds DNA antibody(87.5%), malar rash(80.0%) were the most common findings among the classification criteria by ARA. Microscopic hematuria with proteinuria(75.0%), nephrotic syndrome(55.0%), and microscopic hematuria alone(15.0%) were the most common renal presentations in the respective order at diagnosis. There were 27 cases with WHO class IV lupus nephritis confirmed by renal biopsy and 3 cases with pathological changes of WHO class type. Different treatment modalities were carried out : prednisolone only in 5 cases, prednisol-one+azat-hioprine in 9 cases, prednisolone+azathioprine+intravenous cyclophosphamide in 14 cases, prednisolone+cyclosporine A+intravenous cyclophosphamide in 12 cases, plasma exchange in 9 cases and intravenous gamma-globulin in 2 cases. The average follow-up period was $51.8{\pm}40.5$ months. During $51.8{\pm}40.5$ months. During follow-up, 4 patients expired. The risk factors associated with mortality were male, WHO class IV and acute renal failure at diagnosis. Conclusion: Renal involvement was noted in 63.5% of childhood SLE, and 67.5% of renal lesion was WHO class IV lupus nephritis which is known to be associated with a poor prognosis. Therefore aggressive treatment employing immunosuppressant during the early stages of disease could be helpful in improving long-term prognosis. But careful attention should be given to optimize the treatment due to unique problems associated with growth, psychosocial development and gonadal toxicity, especially in children.

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The Effect of Angiotensin Converting Enzyme Inhibitor on Chronic Cyclosporine Nephropathy in Salt Depleted Rats (저염식이를 이용한 cyclosporine 신독성에서 angiotensin converting enzyme Inhibitor의 영향)

  • Lee Eun-Ju;Lee Eun-Sil;Hah Jung-Hi;Kim Yong-Jin;Park Yong-Hoon
    • Childhood Kidney Diseases
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    • v.4 no.2
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    • pp.127-135
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    • 2000
  • Purpose: Cyclosporine(CsA) is a potent immunosuppressant but the use of CsA is associated with various side effects, especially nephrotoxicity. In tile kidney, salt depletion activates tile renin-angiotensin-aldosteron(RAS) system and accentuates chronic CsA nephropathy. We postulate that angiotensin converting enzyme inhibitors(ACEI) can prevent chronic CsA nephropathy, since ACEI may inhibit this cascades. This study was aimed to assess the effect of ACEI on chronic cyclosporin nephropathy in salt depleted rats. Methods: 36 Fischer-344 rats were divided into 6 goups. Group I received normal salt diet(NSD). Group II received a low salt diet(LSD). Group III received CsA with a NSD. Group IV received CsA with a LSD. Group V received NSD+CsA with ACEI. Group VI received LSD+CsA with ACEI. Rats were sacrificed after six weeks and the glomerular filtration rate(GFR), serum sodium, potassium and whole blood cyclosporine levels were measured. Renal tissues me sampled for the observation of histological changes. Results: No differences in blood CsA level & serum sodium were found between groups during the course of this experiment. Serum potassium in group VI was significantly increased compared with group IV and V (P<0.05). In groups treated with CsA only and in those where CsA was combined with ACEI, GFR was found to be significantly more decreased in LSD than NSD, and GFR in group V was significantly decreased in comparison with group III (P<0.05). Renal histologic lesions associated with CsA which consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles were more severe in tile LSD group. But, no differences were observed between tile groups treated with CsA and ACEI, and the groups treated with only CsA. Conclusion: Salt depletion associated with the activation of the RAS system accentuated chronic CsA nephrotoxicity, but, ACEI could not reduce the functional and morphological changes of salt depleted kidneys, in which nephropathy can be exacerbated in spite of the blocking of the angiotensin II pathway. further studies are required to elucidate whether Am ameliorated the effect of salt-depleted CsA nephrotoxicity upon the effective renal blood flow.

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APOPTOTIC EFFECT IN COMBINATION OF CYCLOSPORIN A AND TAXOL ON ORAL SQUAMOUS CELL CARCINOMA CELL LINE THROUGH THE PI-3 KINASE/AKT1 PATHWAY (구강 편평세포암종 세포주에서 Cyclosporin A와 Taxol 투여시 PI-3 kinase/Akt1 Pathway에 의한 세포사멸 병용효과)

  • Kim, Kyu-Young;Lee, Jae-Hoon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.5
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    • pp.426-436
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    • 2007
  • Oral cancer take up 2-6% of all carcinomas and squamous cell carcinoma, which is the most common type in oral cancer, has a poor prognosis due to its high metastasis and recurrence rates. In treating oral cancer, chemotherapy to the primary, metastasized and recurrent lesion is a very important and useful treatment, even though its widespread usage is limited due to high general toxicity and local toxicity to other organs. Taxol, a microtubule stabilizing agent, is an anticancer drug that induces cell apoptosis by inhibiting depolymerization of microtubules in between the metaphase and anaphase of the cell mitosis. Recently, its effectiveness and mechanism on various tumor has been reported. However, not much research has been done on the application of Taxol to oral squamous cell carcinoma. Cyclosporin A, which is an immunosuppressant, is being used on cancers and when co-administered with Taxol, effectiveness of Taxol is enhanced by inhibition of Taxol induced multidrug resistance. In this study, Cyclosporin A with different concentration of Taxol was co-administered to HN22, the oral squamous cell carcinomacell line. To observe the cell apoptosis and the mechanisms that take part in this process, mortality evaluation of tumor cell using wortmannin, c-DNA microarray, RT-PCR analysis, cytometry analysis and western blotting were used, and based upon the observation on the effect and mechanism of the agent, the following results were obtained: 1. The HN22 cell line viability was lowest when $100{\mu}M$ of Wortmannin and $5{\mu}g/ml$ of Taxol were co-administered, showing that Taxol participates in P13K-AKT1 pathway. 2. In c-DNA microarray, where $1{\mu}g/ml$ of cyclosporine A and 3mg/ml of Taxol were co-administered, no up regulation of AKT1, PTEN and BAD c-DNA that participate in cell apoptosis was observed. 3. When $1{\mu}g/ml$ of Cyclosporin A was applied alone to HN22 cell line, no difference was found in AKT1, PTEN and BAD mRNA expression. 4. Increased AKT1, mRNA expression was observed when $3{\mu}g/ml$ of Taxol was applied alone to HN22 cell line. 5. When $1{\mu}g/ml$ of Cyclosporin A and Taxol($3{\mu}g/ml\;and\;5{\mu}g/ml$) were co-administered to HN22 cell line, PTEN mRNA expression increased, whereas AKT1 and BAD mRNA decreased. 6. As a result of cytometry analysis, in the group of Cyclosporin A($1{\mu}g/ml$) and Taxol($3{\mu}g/ml$) co-administration, increased Annxin V was observed, which shows that apoptosis occurred by deformation of plasma membrane. However, no significant difference was observed with vary ing concentration. 7. In western blot analysis, no caspase 3 was observed in the group of Cyclosporin A($1{\mu}g/ml$) and Taxol($3{\mu}g/ml$) co-administration. From the results of this study, it can be concluded that synergistic effect can be observed in combination therapy of Taxol and Cyclosporin A on oral squamous cell carcinoma cell line, where decreased activity of the cell line was observed. This resulted in decreased AKT1 and BAD mRNA and increased PTEN mRNA expression and when wortmannin and Taxol were co-administered, the viability decreased which confirms that Taxol decreases the viability of tumor cell line. Hence, when Taxol and cyclosporine A are co-administered, it can be assumed that cell apoptosis occurs through AKt1 pathway.

Method Development for Determination of Multi-Mycotoxins in Chicken Liver and Kidney Tissues by LC-MS/MS (LC-MS/MS를 이용한 닭 간과 신장 중 곰팡이 독소 6종 동시분석법 개발)

  • Kim, Soohee;Kim, Kwang-Nam;Kim, Hyobi;Song, Jae-Young;Park, Sung-Won
    • Korean Journal of Poultry Science
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    • v.43 no.2
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    • pp.111-118
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    • 2016
  • Mycotoxins are secondary metabolites produced by molds, such as Aspergillus, Fusarium and Penicillium, that have adverse effects on animals and humans. Aflatoxin, ochratoxin, zearalenone, fumonisin and deoxynivalenol are the mycotoxins of greatest agro-economic importance and cause acute disease called mycotoxicoses. Mycotoxicosis in poultry birds results in decreased meat/egg production, immunosuppressant, and hepatotoxicosis. Some of toxins or their metabolites may be retained in animal or human tissues and induce health problems. This study was designed to develop a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous detection and quantification of mycotoxins, such as aflatoxin $B_1$, aflatoxin $M_1$, ochratoxin A, zearalenone, fumonisin B and deoxynivalenol, in chicken liver and kidney tissues. The mycotoxins were extracted and purified using modified QUECHERS methods, separated by LC and detected by an electrospray ionisation interface (ESI) and tandem MS. Good precision and linearity were observed for most of six mycotoxins. The recovery test for each mycotoxin in liver and kidney tissues mostly indicated good average recovery rates between 80.94% and 98.10% and the coefficient of variation mostly under 13.78%, except for aflatoxin $M_1$ and fumonisin $B_1$. The limit of detection (LOD) for six mycotoxins was $7.6{\sim}145.79{\mu}g/kg$ in liver tissues and $6.07{\sim}197.20{\mu}g/kg$ in kidney tissues. The quantification limits (LOQ) for 6 mycotoxins were in the range $23.04{\sim}441.78{\mu}g/kg$ in liver tissues and $18.40{\sim}597.59{\mu}g/kg$ in kidney tissues, respectively. The developed multi-mycotoxin method in this study permits simultaneous, simple, and rapid determination of several co-existing mycotoxins in chicken liver and kidney tissues.