Effect of acute heat stress on certain immunological parameters in albino rats.

The effect of acute heat stress on certain immunological parameters were studied in male albino rats. The test rats were exposed to an ambient temperature of 40 degrees celsius for 30 minutes and sacrificed immediately. Total WBC count, Differential count, Phagocytic index, NBT reduction, organ weight body weight ratio of spleen, thymus, and popliteal lymph nodes, and soluble immune complex levels were measured in control group and the heat stressed animals. The heat stressed animals show decrease in total WBC count, and neutrophilia, eosinophilia, and lymphocytopenia. The phagocytic index showed a significant increase whereas the avidity index showed a decrease from the control value. NBT reduction was also significant. The soluble immune complex level was not altered. The heat stressed animals showed a decrease in the thymus and spleen weight/body weight ratio while the lymph node/body weight ratio showed an increase compared to the control animals.     

Neuro immuno modulation by ventral hippocampus

Bilateral electrical lesion at ventral hippocampal formation (VHF) did not affect some aspects of nonspecific immunity like total W.B.C. count, percentage of cells in differential count, their absolute count (lymphocyte and neutrophils) and neutrophil functions. The changes observed are due to non-specific craniocerebral trauma as the sham operated animals also showed a similar pattern of response. However the lesion at VHF increases the spleen cell count significantly whereas immunization in these animals decreases the spleen cell count. The thymus weight/body weight ratio also decreases in these animals. Our study confirms the neuroimmuno modulation and the influence of VHF on certain nonspecific immune parameters.     

Immunomodulatory effects of fenugreek (Trigonella foenum graecum L.) extract in mice

Immunomodulatory activity of aqueous extract of Trigonella foenum graecum L., a widely used medicinal and dietary herb, was evaluated in male Swiss albino mice. Mice were treated with three doses of extract (50, 100 and 250 mg/kg body weight per os) for 10 days. Body weight, relative organ weight, cellularity of lymphoid organs, delayed type of hypersensitivity (DTH) response, plaque-forming cell (PFC) assay, haemagglutination titre (HT), quantitative haemolysis of SRBC (QHS) assay, phagocytosis, and lymphoproliferation were studied in various groups of animals. At doses of 50 and 100 mg/kg, a significant increase (p < 0.05) in relative organ weight of thymus was observed but there was no effect on kidney and spleen weights. Liver weight also increased significantly at doses of 100 and 250 mg/kg. However, no elevation in the levels of liver function test (LFT) enzymes was observed. As regards lymphoid organ cellularity, spleen recorded no significant increase at any dose, whereas cellularities of thymus and bone marrow were significantly increased. T. foenum graecum extract elicited a significant (p < 0.001) increase in the DTH response at doses of 50 and 100 mg/kg, but the change at higher dose of 250 mg/kg was not statistically significant. Humoral immunity as measured by PFC showed an elevated response at a dose of 100 mg/kg, but at 50 and 250 mg/kg, no significant effect was observed. In the HT test, plant extract also showed modulatory effect at all the doses. Plant extract elicited a significant increase in phagocytic index and phagocytic capacity of macrophages. Stimulatory response of plant extract was also observed in lymphoproliferation assay but the response was weak. Overall, T. foenum graecum showed a stimulatory effect on immune functions in mice. As it is used for a variety of medicinal purposes, its immunostimulatory effect, as reported in this study, strengthens the rationale of its use in several Ayurvedic and Unani drugs.     

Immunotoxic and cancerostatic effects of ethyl-4-isothiocyanatobutanoate in female Lewis rats with implanted fibrosarcoma

Isothiocyanates (ITCs) have been isolated from plants. Naturally occurring and synthetic ITCs are known as effective chemopreventive agents. Ethyl 4-isothiocyanatobutanoate (E-41B) is a derivative of gamma-aminobutyric acid. Immunotoxic and canocerostatic effects of E-41B in female inbred Lewis rats implanted with experimental fibrosarcoma BP6-TU2 was evaluated in this study. On day 5 after subcutaneous application of tumor cells, animals started to be treated intraperitoneally three times a week with two different doses of E-41B: 28 and 35 mg/kg/day during 28 days. High dose of E-41B was close to maximum tolerated dose (MTD). Control groups of rats with or without tumors injected intraperitoneally only saline or 70% dimethylsulphoxide were added. Administrating of E-41B resulted in suppression of thymus, popliteal lymph node, spleen weight and spleen cellularity. Hematologic evaluation displayed decreased erythrocyte (ERY) count and level of hemoglobin (HB) in rats treated withE-41B. Immune assays--the phagocytic activity of polymorphonuclear leukocytes (PMN) and monocytes, primary antibody response and in vitro proliferative activity of spleen lymphocytes (LY) to mitogens were not significantly affected by E-41B treatment E-41B moderately decreased tumor weights, but this decrease was not statistically significant in comparison with DMSO-exposed rats with tumors. The fibrosarcoma implantation itself increased significantly spleen weight and changed hematological parameters (decreased HB, increased mean cell volume of ERY, increased leukocyte count, increased % PMN, decreased % LY, decreased % EO). Moreover, moderate decreased percentage of CD161+ positive cells (NK cells) were found in peripheral blood. Immune assays showed decline in proliferation of lymphocytes and phagocytic activity of leukocytes. Our findings indicate that administration of E-41B displayed hematoxic effect in rats implanted with fibrosarcoma. Immunotoxic effect was shown as decreased lymphoid organ weight and spleen cytotoxicity although function of immune cells was not impaired.     

Role of corticosteroids in cadmium induced immunotoxicity

Cadmium chloride at doses of 30, 100 and 300 ppm was orally fed to swiss albino mice for 35 days and the humoral and cell mediated immunity was studied by measuring the haemagglutination titre and delayed type hypersensitivity response respectively. Further, the blood corticosteroid level was determined in all the groups. Cadmium at doses of 100 and 300 ppm was found to significantly (p < 0.05) suppress both humoral and cellular immunity with simultaneous increase in the level of blood corticosterone and aldosterone. In order to assess whether the suppression of immune response in cadmium exposed mice is mediated by corticosteroids, aminoglutethemide, an adrenal blocker was administered to mice along with cadmium and the immune response was studied. Aminoglutethemide when administered alone caused significant (p < 0.05) stimulation of immunoglobulin level and delayed type hypersensitivity response as compared to cadmium (300 ppm) fed mice. When co-administered with cadmium, the cadmium induced immunosuppression was reversed back to normal. The results of this study indicate the involvement of adrenal hormones in cadmium induced immunosuppression suggesting that cadmium activates the corticosteroid associated immunoregulatory circuit.     

A study on immunotoxicological effects of subacute amitraz exposure in rats

The effects of amitraz, a formamidine pesticide, were investigated in four-week old outbred male Wistar rats on certain classic toxicological and haematological parameters as well as on specific immune functions. The animals were treated, per os by gavage for 28 days, in a five-day treatment two days break system, with 26.5, 21.1, 10.6 and 5.29 mg/kg/day amitraz. On the 29th day, organ weights of the thymus, heart, lung, spleen, liver, kidneys, adrenals, testicles and popliteal lymph node; WBC and RBC counts, Ht, MCV, haemoglobin; and cell content of the femoral bone marrow were determined. In two separate groups, the effects of amitraz on the PFC content of the spleen, and on the maximum level and time course of DTH reaction, were investigated.Amitraz in 26.5 mg/kg dose increased relative adrenal weight, and decreased relative liver weight, MCV value, PFC content of the spleen, and the maximum level of DTH reaction. The 21.1 mg/kg dose decreased only MCV value, while 10.6 mg/kg elevated the liver-to-brain weight ratio. Based of these findings, a NOEL dose of 5.29 mg/kg was determined for amitraz in this experimental system; while the LOEL doses were 10.6 mg/kg for the general toxicological, 21.1 mg/kg for the haematological and 26.5 mg/kg for the immune function parameters. The results show that the exposure sensitivity of these immune functions to amitraz is lower than that of some other toxicological and haematological parameters.     

Role of Corticosteroids In Cadmium Induced Immunotoxicity

ABSTRACT

Cadmium chloride at doses of 30, 100 and 300 ppm was orally fed to swiss albino mice for 35 days and the humoral and cell mediated immunity was studied by measuring the haemagglutination titre and delayed type hypersensitivity response respectively. Further, the blood corticosteroid level was determined in all the groups. Cadmium at doses of 100 and 300 ppm was found to significantly (p<0.05) suppress both humoral and cellular immunity with simultaneous increase in the level of blood corticosterone and aldosterone. In order to assess whether the suppression of immune response in cadmium exposed mice is mediated by corticosteroids, aminoglutethemide, an adrenal blocker was administered to mice along with cadmium and the immune response was studied. Amino glutethemide when administered alone caused significant (p<0.05) stimulation of immunoglobulin level and delayed type hypersensitivity response as compared to cadmium (300 ppm) fed mice. When co-administered with cadmium, the cadmium induced immunosuppression was reversed back to normal. The results of this study indicate the involvement of adrenal hormones in cadmium induced immunosuppression suggesting that cadmium activates the corticosteroid associated immunoregulatory circuit.     

Immunotoxicological investigations in the mouse: general approach and methods

The adverse effects of chemicals on the lymphoreticular system have generated considerable toxicological interest. In this series of papers, the effects of selected environmentally relevant compounds are reported. This first paper describes the methods and general approach used in judging a chemical's potential risk to the immune system. Risk evaluation was approached utilizing acute, 14- and 90-day studies. Both sexes of the CD-1 random-bred mouse were employed. The immune system was evaluated against a background of more standard toxicological parameters, which included fluid consumption, body and organ weights, hematology, serum and liver chemistries, hepatic microsomal enzyme activities and blood coagulation. Bone marrow status was evaluated by assessing DNA synthesis. Humoral immunity was evaluated by determining the number of IgM spleen antibody-forming cells (AFC) to sheep erythrocytes (sRBC), the serum antibody level to sRBC, and spleen lymphocyte response to the B cell mitogen, lipopolysaccharide (LPS). The status of cell-mediated immunity was assessed by quantitating the delayed type hypersensitivity (DTH) response to sRBC, proliferation of the popliteal lymph node, and the spleen cell response to the T lymphocyte mitogen, Concanavalin A (Con A). Macrophage function was evaluated by measurement of the vascular clearance rate and distribution of radiolabeled sRBC in the liver, spleen, lungs, and thymus, and recruitability, adherence, chemotaxis, and phagocytic activity of peritoneal exudate cells (PEC). Historical control data from six 14- and 90-day studies conducted over a one year period are given. The data resulting from these types of studies can provide a basis for the initial evaluation of a chemical's adverse effect on the immune system.     

酶降解的枸杞多糖免疫增强作用实验研究

目的研究酶降解的枸杞多糖（LBP）对正常小鼠及免疫功能低下小鼠免疫功能的影响。方法酶解法得到中相对分子质量枸杞多糖,分别以50,100,200 mg/kg小鼠灌胃给药,连续10 d,通过免疫器官质量测定、炭粒廓清试验、脾脏T及B淋巴细胞转化试验观察其对免疫功能的影响。注射环磷酰胺造成免疫功能低下模型,测定小鼠的白细胞数、胸腺指数、脾指数,观察其对免疫功能的影响。结果与对照组比较,中、高剂量酶降解的枸杞多糖能增大脾脏指数及胸腺指数（P〈0.01）,能提高吞噬指数及校正吞噬指数（P〈0.05）,能提高B淋巴细胞增殖能力（P〈0.05）;中剂量酶降解的枸札多糖能提高T淋巴细胞增殖能力（P〈0.05）;低、中、高剂量酶降解的枸杞多糖均能提高环磷酰胺模型小鼠的白细胞数、胸腺指数、脾指数（P〈0.05）。结论酶降解的枸杞多糖具有免疫增强作用。     

The effect of acute noise stress on neutrophil functions

The effect of acute noise stress on albino rats was studied by estimating the plasma corticosterone level, total leukocyte count and differential leukocyte count. Neutrophil function was assessed by Candida phagocytosis and Nitroblue tetrazolium reduction test. The total leukocyte count was significantly decreased. No significant changes were observed in the differential count of the leukocytes. A significant increase in the plasma corticosterone level, Candida phagocytosis and Nitroblue tetrazolium reduction was observed indicating acute noise to be a potent stressor in albino rats.     

Rat hippocampus and primary immune response

During immune challenge hippocampal region shows time-dependent changes in neurotransmitter levels. Hence in the present study the effect of electrolytic lesion in the dorsolateral hippocampus (DLH) and ventral hippocampal formation (VHF) (to create a disturbance in neurotransmitter levels) on humoral immunity in albino rats has been studied along with appropriate controls. Haemagglutination titre, IgM and IgG levels were monitored on the 5th day after an immune challenge by sheep red blood cells (SRBC) suspension. Antigen challenged lesioned animals had low circulating antibody titre levels compared with the controls and their site-specific sham lesioned groups. The IgM levels were significantly lowered in both DLH and VHF lesioned and immunized animals compared to their immunized sham groups as well as immunized controls. However, only immunized VHF lesioned group showed a significant decrease in IgG level from their immunized sham group. It was concluded from the results that an intact hippocampal region is essential for the normal humoral immunity for the primary immune response in rats. Probably VHF region may be required for the secondary immune response as indicated by the alteration in IgG levels in these animals.     

Effect of cyclophosphamide on T-lymphocyte marker expression in T-cell areas of some lymphoid organs of the rat

Surface markers on rat lymphocytes from thymus and T-cell areas of lymph node, spleen and Peyer's patches were examined in histological sections after one single dose of Cyclophosphamide (CY, 100 mg/kg body weight). A panel of monoclonal antibodies was used: W3/13, W3/25 and OX8 to investigate Pan T, TH and Ts/c marker expressions respectively. Ts/c marker expression showed a marked and significant reduction in both thymus and lymph node lymphocytes 3 days after CY treatment. This was followed by return to normal in the thymus and a significant rebound increase in the lymph node by day 7 after treatment. This Ts/c marker expression in both the spleen and Peyer's patches showed a significant increase on both day 3 and 7 after CY treatment. Mast cells were observed in large numbers in the thymus and lymph node but not in the spleen and Peyer's patches. TH marker expression was increased significantly in lymph nodes, spleen and Peyer's patches. No change was observed in Pan T marker expression in any of the tissues at any of the times examined.     

Augmentation of immune response by chicoric acid through the modulation of CD28/CTLA-4 and Th1 pathway in chronically stressed mice

This study demonstrates the protective effect of chicoric acid (CA) on chronic restraint stress-induced altered T lymphocyte subset distribution and corresponding cytokine secretion patterns in experimental Swiss albino mice. CA has the potential to restore diminished immune response and Th1/Th2 homeostasis in chronically stressed mice as evident by significant increase in lymphocyte proliferation and CD3⁺, CD4⁺ and CD8⁺ T cell population. Interestingly, chicoric acid imparted immunostimulation mainly by upregulating the expression of CD28 and CD80 and downregulating CTLA-4. It exerted stimulatory effect on IL-12, IFN-gamma and IL-2 and suppressed the increased IL-10 levels in chronically stressed mice. It also exhibited a significant lowering effect on raised corticosterone levels and reversed the chronic stress-induced hypertrophy of adrenal glands and atrophy of thymus and spleen, thereby showing its normalizing effect on HPA axis. Our results reveal that CA has the potential to reverse the impact of chronic restraint stress on immune status by normalizing corticosterone levels and augmenting Th1 cytokine profile along with the co-stimulatory molecules particularly CD28/CTLA-4 pathway that plays a very important role in generation of an effective immune response in immune compromised situations.     

Effect of L-arginine on restraint stress induced modulation of immune responses in rats and mice.

The present study investigates the role of nitric oxide (NO) on restraint stress (RS)-induced modulation of humoral and cell-mediated immune responses in rats and mice. RS produced suppression of humoral immune response, i.e., anti-SRBC antibody titre ( 7.38 +/- 0.32 versus 4.13 +/- 0.30; mean +/- S.E.M., P < 0.001). In case of cell-mediated immunity, in delayed type hypersensitivity (DTH) response the change in paw volume decreased from 0.069 +/- 0.003 mm (mean +/- S.E.M.) in control non-stressed group to 0.038 +/- 0.002 mm in the stressed group (P < 0.001) while percentage leucocyte migration inhibition (% LMI) decreased from 39.7 +/- 1.95 in control non-stressed animals to 15.2 +/- 1.07 in animals subjected to stress (P < 0.01). Pretreating the animals with an NO precursor, L-arginine (1000 mg kg-1, i.p.) antagonized the effect of RS on humoral (anti-SRBC antibody titre 6.50 +/- 0.27 versus 4.13 +/- 0.30, P < 0.001 ) and cell-mediated (DTH response 0.066 +/- 0.002 mm versus 0.038 +/- 0.002 mm, P < 0.001; % LMI 41.5 +/- 1.46 versus 15.2 +/- 1.07, P < 0.01) immune responses. Administration of 7-nitroindazole (7-NI, 50 mg kg-1, i.p.), an inhibitor of neuronal NO synthase, alone further enhanced the immunosuppressive effect of RS (anti-SRBC antibody titre 2.75 +/- 0.25 versus 4.13 +/- 0.30, P < 0.001; DTH response 0.019 +/- 0.002 mm versus 0.038 +/- 0.002 mm, P < 0.001; % LMI 5.0 +/- 1.08 versus 15.2 +/- 1.07, P < 0.01). However, when given before L-arginine treatment, 7-NI reversed the effect of the latter drug on stress-induced immunomodulation (anti-SRBC antibody titre 3.00 +/- 0.27 versus 6.5 +/- 0.27, P < 0.001; DTH response 0.043 +/- 0.003 mm versus 0.066 +/- 0.002 mm, P < 0.001; % LMI 12.0 +/- 0.93 versus 41.5 +/- 1.46, P < 0.01). Unlike its effect on RS-induced immune responsiveness, L-arginine (250, 500, 1000 mg kg-1) when given for 5-7 days to naive non-stressed animals produced dose dependent suppression of both humoral (anti-SRBC antibody titre 6.4 +/- 0.32 versus 5.4 +/- 0.32, 4.0 +/- 0.27, 3.1 +/- 0.30, respectively) and cell-mediated (DTH 0.065 +/- 0.003 mm versus 0.064 +/- 0.004 mm, 0.039 +/- 0.003 mm, 0.020 +/- 0.002 mm, respectively and % LMI 37.52 +/- 1.58 versus 30.48 +/- 1.07, 28.18 +/- 1.22, 19.76 +/- 0.83, respectively) immune responses. 7-NI significantly blocked these immunosuppressive effects of L-arginine (anti-SRBC antibody titre 6.0 +/- 0.38 versus 3.1 +/- 0.030, P < 0.01; DTH response 0.056 +/- 0.004 mm versus 0.020 +/- 0.002 mm, P < 0.001; % LMI 34.76 +/- 1.31 versus 19.76 +/- 0.83, P < 0.01). However, 7-NI when given to non-stressed animals failed to modulate immune responsiveness. Thus, NO appears to play an important role in RS-induced immunomodulation and these effects are different from its effect on immune responsiveness in non-stressed animals.     

雷公藤内酯酮对炎症及免疫功能的影响

目的:研究雷公藤内酯酮(triptonide)对炎症及免疫功能的影响。方法:观察口服给予雷公藤内酯酮对小鼠耳廓急性炎症,毛细血管通透性的影响,以及对小鼠免疫器官指数、碳粒廓清速率、脾细胞抗体、血清溶血素抗体、外周血T淋巴细胞的影响。结果:雷公藤内酯酮1,2,4mg.kg-1能明显抑制小鼠耳廓急性炎症及毛细血管通透性,2,4mg.kg-1能降低胸腺指数、碳粒廓清速率、抑制脾细胞抗体的形成、降低小鼠血清溶血素含量及外周血T淋巴细胞的百分比。结论:雷公藤内酯酮具有抗炎及免疫抑制作用。     

Immunotoxicological Investigations in the Mouse: General Approach and Methods

ABSTRACT

The adverse effects of chemicals on the lymphoreticular system have generated considerable toxicological interest. In this series of papers, the effects of selected environmentally relevant compounds are reported. This first paper describes the methods and general approach used in judging a chemical's potential risk to the immune system. Risk evaluation was approached utilizing acute, 14- and 90-day studies. Both sexes of the CD-I random-bred mouse were employed. The immune system was evaluated against a background of more standard toxicological parameters, which included fluid consumption, body and organ weights, hematology, serum and liver chemistries, hepatic microsomal enzyme activities and blood coagulation. Bone marrow status was evaluated by assessing DNA synthesis. Humoral immunity was evaluated by determining the number of IgM spleen antibody-forming cells (AFC) to sheep erythrocytes (sRBC), the serum antibody level to sRBC, and spleen lymphocyte response to the B cell mitogen, lipopolysaccharide (LPS). The status of cell-mediated immunity was assessed by quantitating the delayed type hypersensitivity (UTH) response to sRBC, proliferation of the popliteal lymph node, and the spleen cell response to the T lymphocyte mitogen, Concanavalin A (Con A). Macrophage function was evaluated by measurement of the vascular clearance rate and distribution of radiolabeled sRBC in the liver, spleen, lungs, and thymus, and recruitability, adherence, chemotaxis, and phagocytic activity of peritoneal exudate cells (PEC). Historical control data from six 14- and 90-day studies conducted over a one year period are given. The data resulting from these types of studies can provide a basis for the initial evaluation of a chemical's adverse effect on the ininiune system.     

Alteration of induced cellular and humoral immune responses by pesticides and chemicals of environmental concern: quantitative studies of immunosuppression by DDT, aroclor 1254, carbaryl, carbofuran, and methylparathion.

Dose-dependent, immunosuppressive effects of continued dietary treatment of rabbits with DDT, Aroclor 1254, carbaryl, carbofuran, and methylparathion were studied. The animals were given a diet containing graded amounts of chemicals for 4 wk and challenged with sheep red blood cells and Freund's adjuvant. The testing followed for an additional 4 wk while the animals were maintained on the same diets as before. The most sensitive indication of immunosuppression was based on evaluation of lymphatic organs, primarily those dependent on thymus-derived lymphocytes. The chemical treatments resulted in a decreased count of plasma cells in popliteal lymph nodes (except with carbaryl), reduction of germinal centers in the spleen, and increasing atrophy of thymus cortex. These responses were generally scaled to increasing levels of the compounds tested. Hemolysin and hemagglutinin titers were not significantly affected by any of the chemical treatments nor were consistent trends observed. The antigen-induced increase in serum γ-globulin was consistently decreased with DDT, Aroclor, carbaryl, and carbofuran treatments, but only carbaryl produced significant changes (at 10 days postantigen). DDT groups showed significantly higher preantigen γ-globulin values which were less evident following antigen challenge. Skin sensitivity to tuberculin was decreased (except with carbaryl) but generally only at high dosages of the test chemicals. None of the compounds showed any effect on growth, food consumption, leucocyte count, or on organ to body weight ratios for liver, kidney, spleen, and adrenal, except for slight liver enlargement caused by Aroclor 1254.     

Suppression of adjuvant arthritis in rats by cholesterol

Dietary cholesterol suppressed adjuvant arthritis, a chronic inflammatory disease, in rats, but did not significantly affect carrageenin edema, an acute inflammation. When rats were fed a high-cholesterol diet beginning 10 days before injection of adjuvant, the development of the adjuvant-induced arthritis was greatly suppressed. Cholesterol feeding prevented hypertrophy of the adrenal gland in arthritic rats, but had little influence on the serum corticosterone level. A significant positive correlation was observed between the adrenal weight and the severity of the arthritis. These findings suggest that the effect of cholesterol feeding is not due to increased adrenal sterol synthesis. Dietary cholesterol also prevented hypertrophy of the spleen, but had no effect on atrophy of the thymus in adjuvant-treated rats. Cholesterol-fed rats showed a significant decrease in the serum lipid peroxide level and a significant increase in the serum copper level. Adjuvant treatment not only enhanced hypercholesterolemia produced by cholesterol feeding, but also the level of free cholesterol in serum. These results suggest that dietary cholesterol may exert some effect on the immune response through changes in spleen and liver functions.     

Modulation of benzene toxicity by an interferon inducer (6MFA)

Repeated intraperitoneal administration of benzene (1.0 ml/kg body wt) for 3 days produced leucopenia, lymphocytopenia and an increased number of nucleated cells in the bone marrow and significantly decreased organ weights of thymus (P less than 0.001) and spleen (P less than 0.001) in female albino rats. Iron content, lipid peroxidation and superoxide dismutase activity of the liver and bone marrow were significantly increased as a result of benzene exposure. Prior administration of 6MFA, an interferon inducer with immunomodulating potential, was found to ameliorate some of the adverse effects of benzene as well as restoration of hepatic architecture histologically. Lipid peroxidation and iron content were both normalised, whereas superoxide dismutase activity was further increased and the number of lymphocytes and bone marrow cells returned to normal. Pretreatment of animals with 6MFA was able to enhance the SRBC antibody titre in benzene-treated immunosuppressed animals. The beneficial effects of 6MFA in the amelioration of the acute toxicity of benzene therefore assume certain significance.     

七味肝胆清颗粒联合头孢哌酮舒巴坦治疗慢性胆囊炎的临床研究

目的 通过连续28 d ig给予昆明小鼠大黄素,进而对其全身毒性和潜在的肝、肾毒性进行评价。方法 40只雄性昆明小鼠随机分成溶媒对照组（0.5% CMC-Na）和大黄素低、中、高剂量（100、300、600 mg/kg）组,最初的最高给药剂量为1 000 mg/kg,从给药第6天起将给药剂量调整为600 mg/kg,每组10只,连续给药28 d后进行解剖,给药后第57天进行恢复期解剖。给药后观察动物的大体症状,并进行体质量和肝、脾、肾、肾上腺及肠系膜淋巴结质量的测定、血清生化指标检测,以及大体和组织病理学检查。结果 给药结束,与溶剂对照组比较,大黄素高剂量组动物的平均体质量在试验的第3、7、10、14、17、21、28天显著降低（P<0.05、0.01、0.001）;中、高剂量组动物血清丙氨酸氨基转移酶（ALT）水平升高,低、中剂量组动物血清天冬氨酸氨基转移酶（AST）水平升高,未见统计学的显著性差异,低、中、高剂量组的其他血清生化指标均未见明显变化;低、中、高剂量组绝对脏器质量及脏器指数均未见统计学的显著性差异。试验期间高剂量组共有6只动物死亡。死亡动物大体剖检可见脾体积减小,胸腺消失。死亡动物肝镜检可见轻度肝细胞坏死、轻度肝细胞变性/坏死伴炎性细胞浸润,以及极轻度色素沉着;肾镜检可见轻度肾小管变性/坏死、轻度肾小管变性/再生,以及轻度色素沉着;脾镜检可见轻度淋巴细胞数目减少和轻度易染体巨噬细胞增多。各组计划剖检动物大体检查未见异常。高剂量组动物肝镜检可见极轻度至轻度色素沉着;肾镜检可见极轻度至轻度色素沉着、极轻度至轻度肾小管变性/再生;胆囊镜检可见极轻度至轻度透明变性、轻度胆囊结石及轻度炎性细胞浸润（中性粒细胞为主）。结论 高剂量的大黄素可对动物产生明显的全身毒性作用,并可造成肝、肾、胆囊、脾损伤,大黄素的胆囊毒性为研究大黄素的肝、胆毒性机制提供新的思路和方向。