Protective effects of gallic acid against nickel-induced kidney injury: impact of antioxidants and transcription factor on the incidence of nephrotoxicity.

Nickel (Ni) is a common metal with a nephrotoxic effect, damaging the kidneys. This study investigated the mechanism by which gallic acid (GA) protects mice kidneys against renal damage induced by Nickel oxide nanoparticles (NiO-NPs). Forty male Swiss albino mice were randomly assigned into four groups, each consisting of ten mice (n = 10/group): Group I the control group, received no treatment; Group II, the GA group, was administrated GA at a dosage of 110 mg/kg/day body weight; Group III, the NiO-NPs group, received injection of NiO-NPs at a concentration of 20 mg/kg body weight for 10 consecutive days; Group IV, the GA + NiO-NPs group, underwent treatment with both GA and NiO-NPs. The results showed a significant increase in serum biochemical markers and a reduction in antioxidant activities. Moreover, levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), phosphorylated nuclear factor kappa B (p65), and protein carbonyl (PC) were significantly elevated in group III compared with group I. Furthermore, the western blot analysis revealed significant high NF-κB p65 expression, immunohistochemistry of the NF-κB and caspase-1 expression levels were significantly increased in group III compared to group I. Additionally, the histopathological inspection of the kidney in group III exhibited a substantial increase in extensive necrosis features compared with group I. In contrast, the concomitant coadministration of GA and NiO-NPs in group IV showed significant biochemical, antioxidant activities, immunohistochemical and histopathological improvements compared with group III. Gallic acid has a protective role against kidney dysfunction and renal damage in Ni-nanoparticle toxicity.

Anti-angiogenic and anti-proliferative activity of ziziphus leaf extract as a novel potential therapeutic agent for reducing hepatic injury in experimental hamster schistosomiasis.

BACKGROUND: Schistosomiasis is one of the most prevalent helminthic infections worldwide. Praziquantel (PZQ) resistance poses a possible danger to the disease's ability to be controlled. Little is known about the role of Ziziphus spina-christi leaf extract (ZLE) in the treatment of hepatic schistosomiasis. However, no study has explored ZLE's anti-angiogenic and anti-proliferative activity as a possible mechanism for reducing hepatic injury in this context. Therefore, this study aimed to evaluate the therapeutic potential of ZLE as an anti-angiogenic, and anti-proliferative agent in hamsters infected with S. mansoni. METHODS: Fifty hamsters were used and divided into 5 groups (10 hamsters each); noninfected untreated (controls), noninfected treated with ZLE, infected untreated, infected treated with PZQ- and infected treated with ZLE. Anti-angiogenic and anti-fibrotic effects of the drugs were assessed pathologically through the immunohistochemical expression of VEGF, Ki-67, and TGF ß1 in liver sections. Some oxidative stress parameters were measured in hepatic homogenates (NO, GSH, GST, and SOD), and serum liver enzymes were also assessed. RESULTS: A significant decrease in worm burden, granuloma size, granuloma area, and numbers in the ZLE- and PZQ-treated groups compared to the infected untreated group, and the decrease in granulomas number and tissue egg load was significantly lower in PZQ treated group compared to ZLE treated group (p<0.05). ZLE exhibited significant anti-angiogenic and anti-fibrotic effects on granulomas, illustrated by significantly lower expression of VEGF and TGF-ß1 than infected untreated and PZQ-treated groups. ZLE exhibits antiproliferative activity evidenced by a significant reduction of positive Ki-67 hepatocytes percentage compared to the infected untreated group. Moreover, ZLE exhibits potent antioxidant effects evidenced by a significantly lowered NO and conservation of hepatic GSH, GST, and SOD in hepatic homogenates compared to infected untreated and PZQ-treated groups (p<0.05). CONCLUSION: Our results point to ZLE as a promising hepatoprotective therapeutic tool in the treatment of schistosome hepatic fibrosis as it has anti-angiogenic, anti-proliferative, anti-fibrotic, and antioxidant effects in hamsters infected with S. mansoni, providing scientific support for its use in conventional medicine.

Fagonia indica ameliorates chromium-induced nephrotoxicity: Role of antioxidant activity and pro-inflammatory cytokines in in-vivo renoprotection.

Chromium (Cr) is an environmental pollutant, has high redox potential, and can exist in various oxidation states, possibly leading to nephrotoxicity. As a potential treatment option, Fagonia indica (F. indica) is an herb remedy traditionally used as a phytomedicine to cure ailments. However, efficient validation of its protective effect and molecular mechanisms has not yet been established. As such, this study aims to investigate the protective effect of F. indica against Cr-induced nephrotoxicity in Swiss mice. Mice were divided into five groups: group I (negative control), group II (F. indica), group III (potassium dichromate [PDC]-treated), group IV (PDC + saline), and group V (PDC + F. indica). Our results demonstrate that group III exhibited decreases in superoxide dismutase (SOD), glutathione s-transferases (GST), glutathione peroxidase (GSH-Px), catalase (CAT), and thioredoxin peroxidase (TPX) levels. Meanwhile, protein carbonyl (PCO) and malondialdehyde (MDA) levels increased in kidney homogenates, increasing the expression of the pro-inflammatory cytokine interleukin-6 (IL-6). This was followed by elevated NF-κB, blood urea nitrogen (BUN), and creatinine serum levels in group III compared with group I. Moreover, histopathological and immunohistochemical examinations demonstrated severe damage to the renal tubular epithelial cells, as well as marked congestion and expressions of caspase-3 and NF-κB. Further, group V showed an improvement in antioxidant activity parameters and reductions in the IL-6, caspase-3, and NF-κB expressions, followed by significant decreases in NF-κB, BUN, and creatinine serum levels. Furthermore, fewer histopathological disturbances were observed compared with untreated group III. Such alterations may be attributed to the antioxidant and anti-inflammatory effects of F. indica. Therefore, our exploration reveals that F. indica is effective in protecting against Cr-induced nephrotoxicity, and it could be applied in the future to human kidney diseases caused by environmental pollutants.

Fagonia indica attenuates chromium-induced nephrotoxicity via antioxidant and anti-inflammatory activities in mice.

Chromium (Cr) is a common environmental pollutant that has wide-ranging toxic manifestations. Fagonia indica (F. indica) is an herbal medicine with anti-inflammatory properties and antioxidant activity. This study aims to evaluate the protective role of F. indica (whole plant) in attenuating Cr-induced nephrotoxicity in Swiss mice. Swiss albino mice were divided into five groups (10 mice in each): group I (control); group II (F. indica-treated); group III (Cr-intoxicated); group IV (Cr- and saline-intoxicated); and group V (Cr-intoxicated and F. indica-treated). Blood samples were drawn after sacrifice for biochemical examinations. Kidney specimens were collected to examine antioxidant activities and conduct histological and immunohistochemical studies for all groups. Mice intoxicated with Cr at 15 mg/kg/b.wt showed a decrease in superoxide dismutase (SOD), glutathione S-transferase (GST), and glutathione peroxidase (GSH-Px) levels compared to the control group, followed by an elevation in the serum IL-6 level. The data revealed severe damage to the renal tubular epithelial cells as well as marked congestion and positive, diffuse, and strong expression of caspase-3 in the dilated tubules. Additionally, the data disclosed an increase in the serum level of blood urea nitrogen (BUN) and creatinine in group III compared with group I. Group V, treated with F. indica at a selected dose of 120 mg/kg/b.wt, showed an improvement in antioxidant activity, attenuation of the IL-6 level, fewer histopathological disturbances, and a statistically significant decrease in the serum level of BUN and creatinine compared with group III. Such changes may be attributed to the antioxidant and anti-inflammatory effects of F. indica. Therefore, our investigation revealed that F. indica effectively protects against Cr-induced nephrotoxicity.

Caffeic acid phenethyl ester mitigates infertility: A crucial role of metalloproteinase and angiogenic factor in cadmium-induced testicular damage.

Cadmium (Cd) is expected to cause deleterious effects on most organs, especially on the male reproductive system. The current study was performed to assess the effect of Cd on fertility in Swiss mice and to evaluate the protective role of caffeic acid phenethyl ester (CAPE) in relieving the detrimental effect of Cd. The mice were divided into four groups of 10: normal Group I received distilled water. Group II, III, and IV were injected 3 mg/kg body weight with Cd intraperitoneally for four consecutive days. Group III received saline. Group IV was treated with 3 mg/kg/day CAPE intraperitoneally for 6 days. Results indicated that CAPE brings about a highly significant improvement in fertility parameters, spermatogenesis, and reduced apoptotic percent. Moreover, metalloprotease-3 (MMP-3) and vascular endothelial growth factor reduced significantly. Overall, our results strongly suggest that CAPE has a protective effect, counteracts the toxic effects of Cd, and prevents testicular injury.

Protective effects of caffeic acid phenethyl ester on cadmium-induced testicular injury: A crucial role of antioxidant enzymes in male mice infertility.

Infertility in men is referred to inability to achieve pregnancy in fertile females after at least one year of regular intercourse. The lack of oxygen in the environment may lead to an imbalance of testes production. Swiss mice were alienated into four groups 10 mice/each. This included one negative normal control group I. The induction of infertility was achieved with injection of cadmium chloride at dose 3 mg/kg body weight for four consecutive days for the rest groups. Group III received vehicle (saline) from the second day of induction for the similar period during the experiment. Infertile mice determined depending on alterations in morphology, motility, and reduced sperm count. Group IV was treated with 3 mg/kg of caffeic acid phenethyl ester (CAPE) per day, for 6 days from the second day of cadmium intoxication. Data showed effectiveness of CAPE significantly through improving the antioxidant enzymes SOD, GST and GSH in testes homogenate and GSH-Px in mice serum that were treated compared to those in the untreated group II (P˂0.001). The histopathology, DNA analysis showed marked improvement in spermatogenesis and DNA intact pattern in treated mice testis. Overall, the results demonstrated the ability of CAPE to improve spermatogenic cells. The data analysis indicated the possibility for the future use of CAPE as an inhibitory agent of infertility. Clinical trials and further studies are required to evaluate the definite medical effects of CAPE based on abundant experimental studies, with predictive future applications in human clinical trials.

Induction of synthesis of matrix metalloproteinases by interleukin-6; evidence for hepatic regeneration following hemi-hepatectomy.

AIM OF THE STUDY: Interleukin-6 (IL-6) can play a role in hepatic regeneration through many mechanisms, one of which is the induction of synthesis of matrix metalloproteinases (MMPs). The aim of the study is to focus on the significance and role of MMPs in the regenerative process to reveal the correlation between IL-6 and MMPs in rats following partial hepatectomy. MATERIAL AND METHODS: Following hemi-hepatectomy, eighty male rats were divided into a control group and a group treated with IL-6 35 µg/100 gm body weight according to a lethality study. The blood samples were drawn from all animal groups for MMP-9 serum level assessment. For the quantitative determination of MMP-9 an enzyme-linked immunosorbent assay (ELISA) was used (Cytoimmune Science Inc., MD) through the quantitative sandwich immunosorbent assay technique. A monoclonal antibody for MMP-9 was pre-coated onto microplate standards. After washing away the unbound substances, an enzyme-linked polyclonal antibody specific for cytokine was added to the wells and color developed in proportion to the amount of total cytokine (pro and/or active) bound in the initial step. The color development was stopped and the intensity of the color was measured. RESULTS: The liver regeneration rate (%) was significantly higher in the group of rats treated with IL-6 (median value was 49.55% vs. 33.20%), p < 0.001. The MMPs' serum level was significantly higher in the group of rats with resection and treatment (median value was 8.01). CONCLUSIONS: These results give evidence for the vital role of MMPs in the process of hepatic regeneration, the level of which, in turn, has a close relationship with the level of IL-6. MMPs have diverse effects in promoting angiogenesis, remodeling of extracellular matrix and endothelial cell proliferation.

Role of interleukin 6 in liver cell regeneration after hemi-hepatectomy, correlation with liver enzymes and flow cytometric study.

AIM OF THE STUDY: Liver regeneration after hemi-hepatectomy may be affected by several growth factors and cytokines. The aim is to evaluate the importance of interleukin 6 (IL-6) in the induction of liver cell regeneration and find correlations with other parameters such as liver enzymes, and DNA analysis by flow cytometric studies. MATERIAL AND METHODS: 80 adult male Sprague-Dawley rats were obtained and divided into two equal groups (n = 40 rats) to undergo 70% partial hepatectomy: group 1 - untreated (control) group; 40 rats not treated; and group 2 - treated group, 40 rats treated with IL-6 35 µg/100 gm body weight according to a lethality study for a period of 4 days, then hepatic resection was carried out according to the steps of Higgins and Anderson. Assessment of liver enzymes and bilirubin level was done. Flow cytometric study was done using a flow cytometer (FACSCalibur; Becton Dickinson) and DNA content was estimated with CellQuest software (Becton Dickinson). RESULTS: The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were significantly higher in the untreated group of rats with liver resection. A higher value of bilirubin was observed in the treated group. Rat weight at sacrification was significantly lower in the group of rats treated with IL-6 than those without treatment, p < 0.001. Liver weight at sacrification was significantly higher in the group of rats treated with IL-6 (p < 0.001). The percentage of apoptotic cells with hypodiploid DNA content was determined from DNA histograms. Untreated rat resected liver showed a peak pattern that represented liver damage with high damage of 73.4%. CONCLUSIONS: Interleukin 6 is of value in induction of liver cell regeneration after seventy percent hemi-hepatectomy as evident by increased liver cell mass, liver enzymes and flow cytometric analysis.

In-vivo antioxidant and anti-inflammatory activity of rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists in animal model of bronchial asthma.

OBJECTIVES: Peroxisome proliferator activated receptor-gamma (PPAR-γ) has been shown to play an important role in the control of immunological and inflammatory responses. This study aims at investigating the potential role of rosiglitazone, a strong PPAR-γ agonist in a murine model of bronchial asthma. METHODS: Adult male guinea pigs were administered ovalbumin 100 mg/kg subcutaneous (SC) and 100 mg/kg intraperitoneal (IP). Treatment with rosiglitazone [5 mg/kg/day, per oral (PO)] was assessed for 21 days. On day 21, the animals were challenged with the same dose of ovalbumin. The forced expiratory volume in 1 s (FEV1 ) to forced vital capacity (FVC), FEV1 /FVC, was measured using a spirometer to diagnosis lung obstruction. Serum levels of interleukin-5 (IL-5) and immunoglobulin E (IgE) were assessed. The activity of superoxide dismutase (SOD) and catalase and the level of reduced glutathione (GSH) were determined in lung tissue homogenates. KEY FINDINGS: Our results demonstrated that treatment with rosiglitazone resulted in a statistically significant improvement in lung function and histopathological features. Significant decrease in the serum levels of IL-5 and IgE were observed. The activity of SOD and catalase as well as the GSH level were significantly increased in the lung tissues of treated animals compared with untreated asthmatic animals. Serum IgE concentrations and IL-5 levels were directly correlated to each other and inversely correlated to the SOD, GSH and catalase levels in the all studied guinea pigs. CONCLUSIONS: Our results provide evidence that the PPAR-γ agonist rosiglitazone may have potential in the development of therapies for bronchial asthma.

Alternative Medicine in Diabetes - Role of Angiogenesis, Oxidative Stress, and Chronic Inflammation.

Diabetes is a chronic metabolic disorder that is characterized by hyperglycemia due to lack of or resistance to insulin. Patients with diabetes are frequently afflicted with ischemic vascular disease and impaired wound healing. Type 2 diabetes is known to accelerate atherosclerotic processes, endothelial cell dysfunction, glycosylation of extracellular matrix proteins, and vascular denervation. Herbal medicines and naturally occurring substances may positively affect diabetes management, and could thus be utilized as cost-effective means of supporting treatment in developing countries. Natural treatments have been used in these countries for a long time to treat diabetes. The present review analyses the features of aberrant angiogenesis, abnormalities in growth factors, oxidative stress, and metabolic derangements relevant to diabetes, and how herbal substances and their active chemical constituents may counteract these events. Evidence for possible biochemical effectiveness and limitations of herbal medicines are given, as well as details regarding the role of cytokines and nitric oxide.

Protective and anti-angiopathy effects of caffeic acid phenethyl ester against induced type 1 diabetes in vivo.

OBJECTIVE: This study aims at investigating the anti-diabetic effects of caffeic acid phenethyl ester (CAPE) against induced immunoregulated diabetes in vivo. METHODS: Swiss mice were administered cyclosporine (CsA) 20mg/kg/day, s.c. for 10 days and simultaneously received multiple low doses of streptozotocin (MLDSTZ) 40mg/kg/day, i.p. for 5 consecutive days. RESULTS: Our results showed that administering CAPE (5µM/kg i.p./every 2 days) to diabetic mice led to a time-dependent decrease in blood glucose levels to 137.1±7.2 from 229.1±12.6mg/dl and induced a significant increase in serum insulin levels by 93.8% compared with untreated ones. An in vivo anti-inflammatory effect of CAPE treated diabetic mice was observed, based on a significant decrease in IL-1ß and IFN-γ (P<0.01) levels and a highly significant reduction in NO (P<0.001). An anti-angiogenic effect of CAPE was observed, as determined by a significant serum matrix metalloproteinase (MMP-9) reduction, angiopoietin (Ang-2) reduction and activation of endostatin serum level in the CAPE treated diabetic mice. Furthermore, histopathological examination showed that destroyed pancreatic islets were regenerated and became free of cell infiltration after treatment. CONCLUSION: CAPE has a significant anti-diabetic effect on mice in vivo. This anti-diabetic effect may be related to its anti-inflammatory and angiostatic effects. It also reduced angiogenic factors which may shift the equilibrium to the angiostatic effect of CAPE. These findings provide the validity of CAPE as anti-diabetic agent in the special model of CsA/STZ and could be relevant in the future for human diabetes.

Inhibitory effect of caffeic acid phenethyl ester on mice bearing tumor involving angiostatic and apoptotic activities.

UNLABELLED: This study aims at investigating the anti-tumor effect of caffeic acid phenethyl ester (CAPE) against animal carcinogenesis. In order to substantiate this fact implanted tumor Ehrlich carcinoma cells were assessed in vivo to Swiss mice strain. We found that administrating of CAPE (15 mg/kg S.C.) showed that the tumor volume decreased significantly by 51%. As a result, it improved animal chances of survival and they became healthier. An anti-angiogenic effect of CAPE in vivo was observed, as determined by a significant serum matrix metalloproteinase (MMP-9) reduction (142.1 ng/ml), activation of endostatin serum level (1.9 ng/ml), as well as DNA fragmentation in tumor treated mice when compared with untreated ones. CONCLUSION: CAPE has a significant inhibitory effect on tumor in vivo. This inhibition may be related to its angiostatic and apoptotic effects. It also reduced angiogenic factors which may shift the equilibrium to the angiostatic effect of CAPE. These findings provide the possibility for the future use of CAPE as tumor therapy in human clinical trials.

Snake venom inhibits the growth of mouse mammary tumor cells in vitro and in vivo.

Crude preparations as well as purified components of venoms isolated from American, Asian and European snakes have been shown to inhibit the growth of some mouse and human cancer cell lines. However, it is not known if Cerastes cerastes venom (CCV) obtained from the Egyptian desert possesses any anti-tumor activity. In the present study we examined in vitro the effect of CCV on the growth rate and morphology of a mouse mammary tumor virus-induced mammary tumor cell line (RIII/Sa-MT). In addition, the effect of the venom on the growth of RIII/Sa-MT cells transplanted into syngeneic mice was investigated. Our results show that CCV at a concentration of 7 microg/ml kills in vitro a significant number of cells (approximately 55%) within a period of 48 h. CCV (1 microg/mouse), administered once per week directly into growing tumors for a period of 4 weeks, was found to reduce tumor load by 54%, and as a consequence the CCV-treated mice lived for more than 35 days longer than untreated mice. Histological and ultrastructural examination of the cells and tumors, as well as nuclear staining of the cells and DNA fragmentation studies, led us to conclude that necrosis is most likely the underlying mechanism by which CCV inhibited the growth of mouse mammary tumor cells both in vitro and in vivo.

Prognostic implication of N-RAS gene mutations in Egyptian adult acute myeloid leukemia.

The pathogenesis of acute myeloid leukemia (AML) involves the cooperation of mutations promoting proliferation/survival and those impairing differentiation. Point mutations of the N-RAS gene are the most frequent somatic mutations causing aberrant signal-transduction in acute myeloid leukemia (AML). The aim of the present work is to study the frequency and prognostic significance of N-RAS gene mutations (N-RASmut) in de novo Egyptian adult AML. Bone marrow specimens from 150 patients with de novo acute myeloid leukemia and controls were analyzed by genomic PCR-SSCP at codons 12, 13 (exon 1), and 61 (exon 2) for N-RAS mutations. In 12.7% (19/150) AML cases, N-RAS gene mutations were found and were observed more frequently in the FAB subtype M4eo (P = 0.028) and with codon 12, 13 (14 of 19; 73.7%). Patients with N-RAS mutation had a significant lower peripheral and marrow blasts (P = 0.004, P = 0.03) and clinical outcome did not improve more than in patients without mutation. In patients with N-RAS gene mutation vs. those without, complete remission rate was (63.2% vs. 56.5%; P = 0.46), resistant disease (15.8% vs. 23.6%; P = 0.51), three years overall survival (44% vs 42%; P= 0.85) and disease free survival (42.1% vs. 38.9%, P = 0.74). Multivariate analysis showed that age was the strongest unfavorable factor for overall survival (relative risk [RR], 1.9; P = 0.002), followed by cytogenetics (P = 0.004). FAB types, N-RAS mutation and leukocytosis were the least important. In conclusion, the frequency and spectrum of N-RAS gene mutation differ between biologically distinct subtypes of AML but do not significantly influence prognosis and clinical outcome in patients with AML.

Insulinotropic and anti-inflammatory effects of rosiglitazone in experimental autoimmune diabetes.

Cytokines and nitric oxide (NO) are involved in the pathogenesis of autoimmune diabetes mellitus (DM). Rosiglitazone is an insulin-sensitizing drug that is a ligand for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-gamma). The anti-inflammatory and immunomodulating properties of PPAR-gamma have been documented. The aim of this study is to investigate the effectiveness of rosiglitazone in autoimmune DM and to clarify the possible mechanism(s) involved. Autoimmune DM was induced in adult male Balb/c mice by co-administration of cyclosporin A and multiple low doses of streptozotocin. Diabetic mice were treated daily with rosiglitazone (7 mg/kg, p.o.) for 21 days. Blood glucose level (BGL), serum insulin level and pancreatic levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and NO were measured. Histopathological examination and immunohistochemical determination of CD4 and CD8 T lymphocytes in the pancreatic islets were performed. In addition, analysis of pancreatic protein expression was carried out. The results showed that rosiglitazone treatment resulted in a significant decrease in the BGL and the pancreatic levels of TNF-alpha, IFN-gamma and NO compared to diabetic mice. The serum insulin level was significantly increased after rosiglitazone treatment compared to diabetic mice. The destroyed pancreatic islets were regenerated and became free from both CD4 and CD8 T cells after treatment. Furthermore, many changes in pancreatic protein expression were observed. These results suggest that rosiglitazone has a beneficial effect in the treatment of autoimmune diabetes, an effect that seemed to be a secondary consequence of its anti-inflammatory and immunomodulating properties and might be reflected at the level of protein expression.

Accelerated neutrophil apoptosis in neutropenic patients with hepatosplenic schistosomiasis is induced by serum Fas ligand.

Neutropenia in patients with hepatosplenic (HS) schistosomiasis may stem from enhanced neutrophil apoptosis. However, the molecular mechanism of neutrophil apoptosis has not been clearly defined. Neutrophils harvested from neutropenic patients with HS schistosomiasis (n = 25), non-neutropenic patients with hepatointestinal (HI) schistosomiasis (n = 10), and age- and sex-matched healthy control subjects (n = 10) were examined for the degree of apoptosis after incubation with autologous sera. Neutrophil apoptosis was quantified by flow cytometry through determination of propidium iodide nuclear staining and confirmed by DNA gel electrophoresis at 0 time (fresh neutrophil), 4 and 24 h culture. Neutrophils from healthy subjects were also incubated with either 10% heterologous normal or neutropenic serum, with and without anti-Fas ligand antibody. Serum Fas ligand levels were assessed in sera of patient groups and healthy controls by ELISA. Compared with normal controls and HI, HS group demonstrated greater neutrophil apoptosis in the presence of autologous serum (P < 0.01, < 0.05, respectively). Furthermore, compared with normal neutrophils exposed to heterologous normal serum, those exposed to heterologous neutropenic serum exhibited higher apoptosis rates (P < 0.01). The apoptotic effect of neutropenic sera is attenuated by anti-Fas ligand. Fas expression was significantly higher in HS group as compared to both HI and normal healthy controls (P < 0.05). Serum Fas ligand levels were significantly higher among HS group as compared to both HI and control groups (P < 0.01 for both). Neutrophil apoptosis was not correlated to the size of spleen in HS group. In conclusion, the rate of neutrophil apoptosis is accelerated in neutropenic HS schistosomiasis. These findings suggest that enhanced neutrophil apoptosis demonstrated in HS patients is triggered by soluble Fas ligand, which is mostly derived from spleen.