Protective effects of indole-3-carbinol on cyclophosphamide-induced clastogenecity in mouse bone marrow cells

Indole-3-carbinol (I3C) is present in many cruciferous vegetables and is known to possess protective properties against chemically induced toxicity and carcinogenesis. In the present study, the antimutagenic potential of I3C has been evaluated using in vivo chromosomal aberration (CA) assay as a cytogenetic end point. Chromosomal analysis was carried out in mouse bone marrow cells following administration of 13C (5 mg/kg; i.p.) for 5 consecutive days. Cyclophosphamide (CP), a well known mutagen, was given at two dose levels of 25 mg/kg b.wt. and 100 mg/kg b.wt., respectively, 24 hours prior to the last dose of I3C. Two groups of five mice each were also injected with CP (25 or 100 mg/kg b.wt.) alone whereas for the vehicle control a group of mice was injected with normal saline only. The results revealed a significant inhibition in the frequencies of CP-induced CAs and aberrant cells in bone marrow cells of I3C-supplemented Swiss albino mice. The antimutagenic potential of 13C towards CP was also evident as the status of mitotic index (MI) was found to show an increment. This study revealed the antigenotoxic potential of I3C against CP-induced chromosomal mutations.     

Oligomerization of indole-3-carbinol in aqueous acid.

Indole-3-carbinol [I3C, also called 3-(hydroxymethyl)indole] is a naturally occurring modulator of carcinogenesis with a biological activity that is at least partially dependent on its conversion to active substances in acidic media. We compared the identities of the major oligomeric products of I3C produced under conditions approximating those found in gastric juice with the reported identities of products of 3-substituted indoles produced under enzymatic and other nonenzymatic conditions. After a 10-min treatment in aqueous HCl solution, I3C was converted in 18% yield to a mixture of acetonitrile-soluble products, the major components of which (as determined by HPLC) were diindol-3-ylmethane (5.9%), 5,6,11,12,17,18-hexahydrocyclononal[1,2-b:4,5-b':7,8-b"]triindo le (2.0%), and [2-(indol-3-ylmethyl)indol-3-yl]indol-3-ylmethane (5.9%). Tentative assignments were made for 3,3-bis(indol-3-ylmethyl)indolenine (0.59%), a symmetrical cyclic tetramer (0.64%), and a linear tetramer (1.1%). Indolo[3,2-b]carbazole (ICZ) was formed slowly in aqueous acidic solutions in low yields (2.0 ppm) which increased to greater than 90 ppm following addition of an organic solvent [tetrahydrofuran (THF) or dimethylformamide (DMF)] to a neutralized solution. Relative yields of trimers vs dimer increased with decreasing pH and with decreasing starting concentration of I3C. Evidence is presented that ICZ formation may not involve radical intermediates as is characteristic of photodynamic processes. A mechanistic rationale is presented for the formation of the identified products.     

Dietary indole-3-carbinol alters immune functions in rats

To further elucidate the physiological mechanisms that may contribute to the dichotomy of effect of indole-3-carbinol (I3C) on cancer development, we examined immune functions representative of the three major branches of the immune system in rats fed either a high (150 mg/kg) or low (50 mg/kg) dose of I3C. Animals fed the high dose of I3C daily for 7 wk had significantly reduced natural killer cell activity. In contrast, T-cell-mediated delayed-type hypersensitivity was significantly elevated. Antibody production in response to the antigen keyhole limpet hemocyanin was not significantly altered compared to controls. These results indicate that exposure to I3C may have differential effects on major immune responses. The significance of these immune function alterations in tumor development will require additional investigation of the effects of dietary I3C on immune functions in appropriate tumor models.     

Assessment of chromosomal aberration in the bone marrow cells of Swiss Albino mice treated by 4-methylimidazole

4-Methylimidazole (4-MEI) is formed during the production of certain caramel coloring agents used in many food and drink products. It may also be formed during the cooking, roasting, or other processing of some foods and beverages. So it was unintentionally consumed in worldwide. This study was aimed to investigate the genotoxic and cytotoxic effects of 4-MEI using chromosome aberration (CA) and mitotic index (MI) in Swiss Albino mice. In this research, CA and MI of the mouse bone marrow cells were analyzed after treating the animals with 4-MEI (100, 130 and 160 mg/kg) for 12 h and 24 h treatment times. All data were analyzed using statistical methods. 4-MEI significantly increased the percentage of CAs at all concentrations for 12 h and at highest concentration for 24 h treatment periods. 4-MEI at highest concentration for 12 h and at all concentrations for 24 h decreased the MI in comparison with control. Genotoxic and cytotoxic effects of 4-MEI at 24 h treatment periods were concentration dependent. Consequently, it can be said that 4-MEI have genotoxic and cytotoxic effect in mouse.     

Endocrine disruption by indole-3-carbinol and tamoxifen: blockage of ovulation

Immature Sprague-Dawley rats received daily doses of indole-3-carbinol (I3C, 0-1.5 g/kg/day), 3,3'-diindolymethane (DIM, 0-400 mg/kg/day), tamoxifen (TAM, 0-0.5 mg/kg/day), or vehicle to determine if their antiestrogenic effects occur by the same mechanism and whether I3C's action is mediated by DIM. Follicular development was induced on day 24 of age by equine chorionic gonadotropin (eCG, 5 IU) 1 day after the initial dose. In a hormone replacement study, human chorionic gonadotropin (hCG, 10 IU sc, 48 h post-eCG) was used to mimic a normal preovulatoy luteinizing hormone (LH) surge following treatment with either I3C or TAM. Blood and ovaries were collected throughout follicular development and the number of ova shed was measured on the morning following expected ovulation (72 h post-eCG). I3C but not TAM reduced body weight gain at higher doses after 4 days of dosing. Ovarian weight gain and ovulation were inhibited by both I3C and TAM in a dose-dependent fashion. During the preovulatory period, both I3C and TAM blocked normal LH and follicle-stimulating hormone (FSH) surges and suppressed serum progesterone (P(4)) profoundly without changing circulating levels of estrogen (E(2)). At the time of expected ovulation, serum E(2) was increased in rats receiving I3C or tamoxifen, whereas serum P(4) was dose-dependently decreased. DIM exerted no significant effects on any of the endpoints studied, even at the highest dose, indicating that the antiestrogenic effects of I3C are not mediated by this metabolite of I3C. hCG successfully restored ovarian weight gain and ovulation in TAM-treated rats. However, hCG only partially reversed the blockage of ovulation by I3C, although ovarian weight gain was restored to normal. In summary, both I3C and TAM block ovulation by altering preovulatory concentrations of LH and FSH, but I3C appears to exert its effect(s) by (a) different mechanism(s) of action. I3C seems to act at both the ovarian and hypothalamic levels by mechanisms similar to those seen in TCDD-treated rats, whereas TAM appears to act only on the hypothalamic-pituitary axis as an anti-estrogen.     

3-吲哚甲醇的抗肿瘤作用

目的 探讨硫代葡萄糖苷的降解产物3-吲哚甲醇(IC)在体内、外的抗癌活性,为十字花科蔬菜的防癌作用以及从蔬菜中筛选药用成分提供理论依据.方法 体内试验以荷瘤小鼠实体瘤重、抑瘤率及对脾脏、胸腺指数的影响为指标,评价IC对S180移植性肉瘤的抑制作用;长期实验在饮水中加入化学致癌剂甲硝基亚硝基胍(MNNG),诱发小鼠前胃鳞癌及癌前病变,同时给予不同剂量IC进行预防,观察癌前病变和癌变发生率;体外采用MTT法,观察IC对HeLa细胞增殖的抑制作用.结果 IC在体内能明显抑制实体瘤重,使荷瘤小鼠的脾脏和胸腺指数下降,表现出一定的免疫抑制作用;长期试验能明显降低MNNG诱发的癌前病变和癌变发生率;在体外对HeLa细胞有明显的生长抑制作用,且作用随药物浓度增加而加大.结论 IC具有一定的抗肿瘤活性.     

Intervention in free radical mediated hepatotoxicity and lipid peroxidation by indole-3-carbinol

The cytoprotective effect of the natural dietary constituent indole-3-carbinol (I-3-C) on carbon tetrachloride (CCl4) mediated hepatotoxicity in mice was examined. I-3-C pretreatment by gavage 1 hr prior to intraperitoneal injection of CCl4 produced a 63% decrease in CCl4-mediated centrolobular necrosis and a related 60% decrease in plasma alanine aminotransferase activity (a marker of liver necrosis). Since the toxicological effects of CCl4 are mediated by radical species generated during reductive metabolism by cytochrome P-450, we examined the potential ability of I-3-C to scavenge reactive radicals. Three systems were used to evaluate the ability of I-3-C to intervene in free radical mediated lipid peroxidation. These systems consisted of the following: (1) phospholipid dissolved in chlorobenzene, with peroxidation initiated by the thermal and photo decomposition of azobisisobutyronitrile (AIBN); (2) sonicated phospholipid vesicles in phosphate buffer (pH 7.4), with peroxidation initiated by ferrous/ascorbate; and (3) mouse liver microsomes containing an NADPH-regenerating system, with peroxidation initiated with CCl4. Lipid peroxidation was measured in these three systems as thiobarbiturate-reacting material. In the AIBN and ferrous/ascorbate systems, I-3-C inhibited lipid peroxidation, with greater inhibition under conditions of low rates of free radical generation. I-3-C was not as effective an antioxidant as butylated hydroxytoluene (BHT) or tocopherol, but it inhibited peroxidation in a dose-response manner. I-3-C was most effective as a radical scavenger in the microsomal CCl4-initiated system by inhibiting lipid peroxidation in a dose-dependent fashion, with 50% inhibition at 35-40 microM I-3-C. This concentration is about one-third of the concentration of I-3-C achieved in liver after treatment of mice by gavage with 50 mg I-3-C/kg body weight. These data suggest that I-3-C may be a natural antioxidant in the human diet and, as such, may intervene in toxicological or carcinogenic processes that are mediated by radical mechanisms.     

Modulation of P-glycoprotein-mediated multidrug resistance in K562 leukemic cells by indole-3-carbinol

Resistance to chemotherapeutic drugs is one of the major problems in the treatment of cancer. P-glycoprotein (P-gp) encoded by the mdr gene is a highly conserved protein, acts as a multidrug transporter, and has a major role in multiple drug resistance (MDR). Targeting of P-gp by naturally occurring compounds is an effective strategy to overcome MDR. Indole-3-carbinol (I3C), a glucosinolates present in cruciferous vegetables, is a promising chemopreventive agent as it is reported to possess antimutagenic, antitumorigenic, and antiestrogenic properties in experimental studies. In the present investigation, the potential of I3C to modulate P-gp expression was evaluated in vinblastine (VBL)-resistant K562 human leukemic cells. The resistant K562 cells (K562/R10) were found to be cross-resistant to vincristine (VCR), doxorubicin (DXR), and other antineoplastic agents. I3C at a nontoxic dose (10 x 10(-3) M) enhanced the cytotoxic effects of VBL time dependently in VBL-resistant human leukemia (K562/R10) cells but had no effect on parent-sensitive cells (K562/S). The Western blot analysis of K 562/R 10 cells showed that I3C downregulates the induced levels of P-gp in resistant cells near to normal levels. The quantitation of immunocytochemically stained K562/R10 cells showed 24%, 48%, and 80% decrease in the levels of P-gp by I3C for 24, 48, and 72 h of incubation. The above features thus indicate that I3C could be used as a novel modulator of P-gp-mediated multidrug resistance in vitro and may be effective as a dietary adjuvant in the treatment of MDR cancers.     

Fate of indole-3-carbinol in cultured human breast tumor cells

Indole-3-carbinol (I3C), a natural component of Brassica vegetables, is a promising cancer preventive agent that can reduce the incidence of tumors in reproductive organs when administered in the diet. Here we report on the metabolic fate of radiolabeled I3C in MCF-7 cells. I3C was surprisingly inert to metabolism by these cells with a half-life in medium of approximately 40 h. [(3)H]I3C levels in media declined at a similar rate whether incubation was with cultured cells or in cell-free medium. Neither [(3)H]I3C nor its modified products accumulated in MCF-7 cells and only low levels of intact I3C were detected in cellular fractions. In contrast, I3C represented over 30% of the radioactivity in media even after 72 h. In cytosolic fractions, the 3-(cystein-S-ylmethyl) and 3-(glutathion-S-ylmethyl) conjugates of [(3)H]I3C were the primary conversion products identified after 16 h, representing approximately 50% and approximately 15% of the radioactivity in these fractions, respectively. The reaction of I3C with thiols appears to be nonenzymatic since the cysteine conjugate is produced when I3C is incubated in cell-free medium containing additional cysteine. Both cellular and extracellular proteins were nonspecifically modified with [(3)H]I3C. In medium, proteins are radiolabeled even in the absence of cells, indicating again that enzymatic activation was not required. I3C was also oxidized to indole-3-carboxaldehyde and indole-3-carboxylic acid in culture medium independent of cells. Unexpectedly, 3,3'-diindolylmethane (DIM), an I3C product with in vitro and in vivo biological activity, was detected in cellular fractions and appeared to accumulate in the nucleus, representing approximately 40% of this fraction after 72 h treatment. These findings suggest that MCF-7 cells do not vigorously metabolize I3C and that the major route of reaction is with cellular thiols such as glutathione and proteins. The accumulation of DIM in the nucleus suggests that this product may have a role in the cellular biological activities of I3C.3     

Nucleophilic index value: implication in the protection by indole-3-carbinol from N-nitrosodimethylamine cyto and genotoxicity in mouse liver

A novel assay system was developed in order to quantitate the nucleophilicity of pure chemicals or tissue extracts. This Nucleophilic Index Value (NIV) assay was based on the ability of putative nucleophiles to inhibit the methylation of cysteine by limiting concentrations of the electrophilic source, N-methyl-N-nitrosourea (MNU). Efficacy of model and cellular nucleophiles was quantitated as nmol cysteine protected by the nucleophile from methylation by MNU/h/mM compound. The NIVs of the pure compounds ascorbate, glutathione, 4-(4-nitrobenzyl)-pyridine (NBP) and indole-3-carbinol (I-3-C) were 2400, 1600, 3 and 0, respectively. When mice were treated with I-3-C by gavage at dosages of 0, 25, 50, 75 or 100 mg/kg body wt, the NIV for ethyl acetate extracts of the livers 1 h after treatment were 0, 33, 47, 52 and 92 nmol cysteine preserved/h/g tissue, respectively. The I-3-C enhancement of NIV was not attributable to ascorbate or glutathione, neither of which were present in the ethyl extracts of liver. When mice were treated with 10 mg N-nitrosodimethylamine (NDMA)/kg body wt 1 h after the varying dosages of I-3-C, the 24 h post-NDMA plasma alanine transaminase (ALT) values were decreased by I-3-C pretreatment in a dose-dependent fashion. Plasma ALT values were used in this study as an indicator of hepatotoxicity. The coefficient of determination, r2, computed from the linear least squares correlation coefficient between NIV and ALT values, was 0.80 (0-100 mg I-3-C/kg) and 0.97 (0-75 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)     

The micronutrient indole-3-carbinol: implications for disease and chemoprevention

This review provides a historical perspective for the development of indole-3-carbinol (I-3-C) as a chemopreventive or therapeutic agent. Early experiments in animal models clearly showed that feeding cruciferous vegetables reduced the incidence of chemical carcinogenesis. Excitement was generated by the finding that these vegetables contained a high content of indole-containing compounds, and I-3-C could by itself inhibit neoplasia. The mechanism of action was linked primarily to the ability of I-3-C and derived substances to induce mixed-function oxidases and phase II antioxidant enzymes by binding and activating the aryl hydrocarbon receptor. Most of the literature on chemoprotection by dietary indole compounds relates to this mechanism of action. Other mechanisms, however, are notable for this class of compounds, including their ability to act as radical and electrophile scavengers; the various ascorbate conjugates of I-3-C (ascorbigens) may be important in this regard. Exciting recent findings have demonstrated that I-3-C and its reaction products can affect cellular signaling pathways, regulate the cell cycle, and decrease tumor cell properties related to metastasis. It does not appear that I-3-C per se is the primary active compound in chemoprotection or chemoprevention. Rather, I-3-C and ascorbate provide the parent compounds for the formation of a myriad of nonenzymatic reaction products that have strong biological potency. We conclude with our thoughts regarding the current status and future directions for the use of I-3-C and related compounds.     

Genotoxicity assessment of S-equol in bacterial mutation,chromosomal aberration,and rodent bone marrow micronucleus tests

Intervention studies in man have shown that dietary soy isoflavones may provide certain health benefits. One of the possible reasons for this benefit is that the daidzein contained in soy is converted to S-equol. As part of a drug development program for S-equol, three genotoxicity studies were conducted. The studies comprised bacterial mutation, chromosomal aberration, and in vivo bone marrow micronucleus tests conducted according to Good Laboratory Practices (GLP). No evidence of genotoxic activity was observed in the in vitro tests at concentrations up to those associated with cell toxicity. In addition, no evidence of cytotoxicity or genotoxicity was seen in the rat bone marrow micronucleus test in animals dosed at levels up to the standard limit of 2000 mg/kg. It is concluded that S-equol is not active in the standard battery of genotoxicity assays recommended by the International Conference on Harmonisation (ICH) for registration of new pharmaceuticals. The current results support the further development of S-equol.     

Indole-3-carbinol and indole-3-acetonitrile influence on hepatic microsomal metabolism

Mice, rats, and rabbits were injected ip or gavaged for 10 days with indole-3-carbinol (IC) or indole-3-acetonitrile (IAN), two major indoles in cruciferous vegetables. The metabolic response of hepatic microsomes was compared with those of animals receiving the standard inducing agents, phenobarbital (PB), β-naphthoflavone (NF), and Aroclor 1254 (Ar). Rat and mouse liver microsomes exhibited increases in cytochrome P-450 and benzo[a]pyrene (BaP) oxidase activity after IC treatment, but rabbit microsmes were not affected. IAN was without effect on cytochrome P-450 or BaP oxidase activity in all three species. In mouse, gavage with IC produced a 61% decrease in zoxazolamine paralysis time, increased the extinction coefficient for binding IC to hepatic microsomes, and decreased the wavelength for maximum absorbance of the CO-reduced minus reduced difference spectrum. Furthermore, gavage with IC produced clear significant increases in several hepatic microsomal enzyme activities, including ethoxyresorufin O-deethylase. All of the alterations observed following IC gavage paralleled those following NF or Ar induction, but were dissimilar from the changes observed after PB administration. These data suggest that dietary IC may act as a moderate inducing agent for hepatic cytochromes P-448 (NF-inducible forms).     

The stability of the nitrosated products of indole, indole-3-acetonitrile, indole-3-carbinol and 4-chloroindole

The nitrosation rates of indole-3-acetonitrile, indole-3-carbinol, indole and 4-chloroindole and the stability of their nitrosated products were investigated. Each of the nitrosated indole compounds was directly mutagenic to Salmonella typhimurium TA100 in the following order of potency: 4-chloroindole much greater than indole-3-carbinol greater than or equal to indole greater than indole-3-acetonitrile. Total N-nitroso determinations, carried out according to a modified method of Walters et al. (Analyst, Lond. 1978, 103, 1127), and Ames test results revealed that each of the indole compounds immediately formed mutagenic N-nitroso products upon nitrite treatment under acidic conditions. However, the nitrosation rates of indole and 4-chloroindole were higher than those of indole-3-acetonitrile and indole-3-carbinol. For indole-3-carbinol, indole-3-acetonitrile and indole, no change in the amount of nitrosated products was observed at increasing incubation times from about 15 up to 60 min. For 4-chloroindole the amount of nitrosated products decreased with increasing incubation times. In all cases the responses in the Ames test paralleled the amounts of nitrosated products. The stabilities of the nitrosated products of the indole compounds were investigated at pH 2 and 8. Both mutagenicity data and measurements by high-performance liquid chromatography using a photohydrolysis detector indicated that the nitrosation products of indole-3-acetonitrile, indole-3-carbinol and indole were more stable at pH 8 than at pH 2. Conversely, nitrosated 4-chloroindole was stable at pH 2 but not at pH 8. The pH 8 chromatograms showed a large nitrite peak. From this we hypothesized that the presence of free nitrite might be responsible for the stability of nitrosated indole-3-acetonitrile, indole-3-carbinol and indole at pH 8. Experiments confirmed the existence of an equilibrium between the nitrosated indole compound and the free indole compound plus nitrite.     

吲哚-3-原醇对乙醛所致精密肝切片中星状细胞活化的影响

目的利用精密肝切片(PCLS)技术,研究吲哚-3-原醇(I3C)对乙醛活化肝星状细胞(HSCs)的作用及其机制。方法将200～800μmol.L-1的I3C及700μmol.L-1乙醛与PCLS共同孵育6h,免疫组化法分析肝切片中α-平滑肌肌动蛋白(α-SMA)表达,并检测培养液中谷胱甘肽S-转移酶(GST)和乳酸脱氢酶(LDH)活性、转化生长因子-β1(TGF-β1)含量、基质金属蛋白酶-1(MMP-1)及基质金属蛋白酶抑制物-1(TIMP-1)表达量及组织丙二醛(MDA)和羟脯氨酸(Hyp)含量。结果200～800μmol.L-1I3C可不同程度的减少乙醛激活的HSCs,并可明显降低乙醛升高的培养液中GST、LDH活性和肝组织中MDA和Hyp含量(P<0.05或P<0.01),呈良好的浓度依赖性。I3C给药组与乙醛对照组比较,培养液中TGF-β1含量降低(P<0.01),MMP-1/TIMP-1蛋白表达比值升高(P<0.01)。结论I3C能有效拮抗乙醛所致的HSCs活化,其机制与降低细胞氧化应激和促进基质胶原降解有关。     

吲哚-3-原醇对猪血清诱导大鼠肝纤维化的治疗作用

研究吲哚-3-原醇(I3C)对猪血清诱导大鼠肝纤维化的治疗作用及其机制。腹腔注射猪血清制备大鼠肝纤维化模型,造模成功后用I3C治疗17天。采用HE和Masson三色染色法分别观察肝脏病理学和胶原含量改变;生化比色法测定肝组织羟脯氨酸(Hyp)含量;免疫组织化学法观察肝脏中α-平滑肌肌动蛋白(α-SMA)的表达。进一步培养大鼠肝星状细胞株HSC-T6,用13C处理24 h后,FITC-Annexin V/PI双重染色法检测细胞凋亡;实时荧光定量PCR法检测细胞凋亡相关蛋白Bax和Bcl-2的mRNA表达。结果显示,与模型对照组比较,各I3C治疗组的肝组织Hyp含量不同程度降低,肝细胞损伤减轻,胶原纤维沉积减少(P<0.01),α-SMA表达降低(P<0.01)。细胞实验显示,I3C可明显增加HSC-T6细胞凋亡率,升高Bax/Bcl-2的mRNA表达(P<0.05)。以上结果说明,I3C对猪血清诱导大鼠肝纤维化有一定治疗作用,可能与其诱导活化HSC凋亡继而促进基质胶原降解有关。     

Putative mechanisms of action for indole-3-carbinol in the prevention of colorectal cancer

Background: Multiple factors are known to contribute to the development of cancer and numerous agents have been shown to confer some protection. Diets high in vegetables, especially cruciferous vegetables (broccoli, Brussels sprouts, cabbage etc.) provide such protection. Objective: To define the phytonutrients within this group of vegetables and how their chemoprotective properties might be conferred. Methods: Cruciferous vegetables provide the only human dietary source of a class of phytonutrients, the glucosinolates. The glucosinolate breakdown products, which include indole-3-carbinol and sulforaphane, have demonstrated various anticancer actions in laboratory studies. We give a brief overview of current understanding of the chemopreventive pathways for indole-3-carbinol in various human cancers and how this may relate, in particular, to colorectal cancer; the supporting evidence; and our opinion of its anticancer properties. The review is limited by the lack of bioavailability data in humans. Results: Indole-3-carbinol interacts with a multitude of intracellular processes, which may halt tumourgenesis and induce apoptosis.     

吲哚-3-原醇对博莱霉素所致小鼠肺纤维化的干预作用及其机制

目的观察吲哚-3-原醇(indole-3-carbinol,I3C)对博莱霉素致小鼠肺纤维化的干预作用并初步探讨其机制。方法Imprinting Control Region(ICR)小鼠随机分为6组:正常组、模型组、醋酸泼尼松组(6.67 mg.kg-1)、吲哚-3-原醇小、中、大剂量组(25、50、100 mg.kg-1)。小鼠气管内注射博莱霉素制备肺纤维化模型后,第2天给予相应药物,每天1次。连续给药28 d后处死小鼠检测其肺系数、血清和肺组织羟脯氨酸(Hydroxyproline,HYP)、血清总抗氧化能力(To-tal antioxidative capacity,T-AOC);取固定部位肺组织切片HE染色,进行病理学观察;RT-PCR法检测肺组织中α-SMA、CollagenⅠ、TGF-β、Smad2 mRNA的表达;Western blot法检测肺组织中α-SMA、TGF-β、Smad2蛋白的表达。结果吲哚-3-原醇能够提高小鼠血清的总抗氧化能力(P<0.05或P<0.01),同时可以降低肺系数和肺组织中的HYP含量(P<0.05或P<0.01);光镜观察表明吲哚-3-原醇能明显减轻肺纤维化小鼠肺泡炎和肺纤维化程度(P<0.05或P<0.01);RT-PCR检测发现吲哚-3-原醇能明显降低肺组织α-SMA、CollagenⅠ、TGF-β、Smad2基因表达水平(P<0.05或P<0.01);Western blot分析结果说明吲哚-3-原醇能明显降低肺组织α-SMA、TGF-β、Smad2蛋白表达(P<0.05或P<0.01)。结论吲哚-3-原醇可能通过抑制TGF-β/Smad信号通路来减轻博莱霉素致小鼠肺纤维化。