Nitric Oxide, Neutrophil/Lymphocyte, and Platelet/Lymphocyte Ratios as Promising Inflammatory Biomarkers in Complicated Crohn's Disease: Outcomes of Corticosteroids and Anti-TNF-α Therapies.

Crohn's disease (CD) is a relapsing-remitting inflammatory bowel disease with a progressive course. The aim of our study was to evaluate the relationship between nitric oxide (NO), pro-inflammatory cytokines, and blood count-based ratios in patients with complicated Crohn's disease as well as the outcome of corticosteroid or anti-TNF-α therapy. In this context, we evaluated the NLR as the ratio of neutrophils count to lymphocytes count, PLR as the ratio of platelets count to lymphocytes count, and MLR as the ratio of monocytes count to lymphocytes count in patients and controls. Furthermore, we assessed NO production by the Griess method in plasma along with iNOS and NF-κB expression by immunofluorescence method in intestinal tissues of patients and controls. In the same way, we evaluated plasma TNF-α, IL-17A, and IL-10 levels using ELISA. Our results indicate that blood count-based ratios NLR, PLR, and MLR were significantly higher in patients compared to controls. In addition, increased systemic levels of NO, TNF-α, and IL-17A and colonic expression of iNOS and NF-κB were observed in the same patients. Interestingly, the high ratio of NLR and MLR as well as NO production were significantly decreased in treated patients. Collectively, our findings suggest that nitric oxide as well as the blood count-based ratios (NLR, PLR, MLR) could constitute useful biomarkers in complicated Crohn's disease, predicting the response to treatments.

Hepatic inflammation and liver fibrogenesis: A potential target for the treatment of cystic echinococcosis-associated hepatic injury.

To investigate the effect of cystic echinococcosis (CE) on liver damage, we developed a secondary experimental echinococcosis in Swiss mice by intraperitoneal inoculation of viable protoscoleces. Mice were randomly allocated into three groups: Ctrl group, PBS group, and CE group. Mice were euthanized and associated indications were investigated to evaluate inflammatory and fibrotic responses in liver. Hepatic damage and fibrotic reaction were histologically analyzed. The hepatic expression of iNOS, TNF-α, NF-κß, vimentin, Bcl-2 and CD68 was evaluated by Immunohistochemical examinations. Interestingly, a significant iNOS, TNF-α, NF-κß, vimentin, Bcl-2 and CD68 increase levels was observed in liver tissue and pericystic layer of hepatic hydatid cyst and correlate with the abundance of collagen and reticulin fibers. These observations could promote a potential target for the treatment of CE-associated hepatic injury.

Beneficial effect of dimethyl fumarate on experimental autoimmune uveitis is dependent of pro-inflammatory markers immunomodulation.

Autoimmune uveitis is an inflammatory disease of the eye and is one of the major causes of blindness worldwide. Experimental autoimmune uveoretinitis (EAU) constitutes an animal disease model of human endogenous uveitis. In our study, we investigated the immunomodulatory effect of dimethyl fumarate (DMF) using bovine retinal extract-induced uveitis in a Female Wistar rats. To evaluate the in vivo efficacy, Female Wistar rats were divided into seven experimental groups: control group (n = 5), consisting of non-immunized animals; Uveoretinitis (n = 5), and DMF/Uveoretinitis groups (n = 15), which received a subcutaneous injection of bovine retinal extract emulsified in complete Freund's adjuvant; MC group (n = 5), treated by daily intragastric administration of methylcellulose 0.08% in tap water; DMF group, consisting of control positive group, rats received daily oral gavage administration of 500 µL of dimethyl fumarate at 100 mg/Kg dissolved in 0.08% methylcellulose in tap water (n = 5). On day 14 post immunization, the rats were then euthanized and associated indications were investigated to evaluate the therapeutic efficacy. Nitric oxide (NO) and TNF-α were assessed in plasma. Meanwhile, eyes were collected for histological and immunohistochemical studies. The retinal expression of iNOS, CD68, CD20, CD25, CD4, and CD8 was examined. Interestingly, DMF enhanced a significant reduction of NO and TNF-α production in the treated group. This effect was strongly related to the histological structure of eyes improvement. In the same context, a significant decrease of iNOS, CD68, and CD20 expression and CD25 increase expression were reported in retinal tissue of DMF/Uveoretinitis group in comparison to the immunized group. Collectively, our results indicate that DMF treatment has a beneficial effect in experimental autoimmune uveoretinitis and could constitute a good candidate for monitoring an ocular inflammatory diseases.

A preventive effect of the combination of albendazole and pomegranate peel aqueous extract treatment in cystic echinococcosis mice model: An alternative approach.

To investigate the preventive effect of the combination of albendazole (ABZ) and pomegranate peel aqueous extract (PGE) treatment in cystic echinococcosis, we assess in vivo the antihydatic and the anti-inflammatory effects of the combination of ABZ/ PGE in cystic echinococcosis mice model. To evaluate the in vivo efficacy, mice were inoculated intraperitoneally with viable protoscolices and then treated with ABZ and/or PGE during cystic echinococcosis development. Mice were randomly allocated into eight groups: ABZ/CE group, PGE/CE group, (ABZ+PGE)/CE group, CE group, and control groups (Ctrl, PBS, ABZ, and PGE groups). Drugs in diverse treated groups were orally administered daily during CE development for two months. Mice were then euthanized and associated indications were investigated to evaluate the therapeutic efficacy. Cyst development and hepatic damage were macroscopically and histologically analyzed. The hepatic expression of iNOS, TNF-α, NF-κß, vimentin, and CD68 was examined. Interestingly, the association of ABZ and PGE enhanced a significant reduction of the rate of hydatid cyst growth inhibition in comparison to the infected or ABZ-treated groups. This effect was strongly related to the histological structure of liver improvement. A significant iNOS, TNF-α, NF-κß, vimentin, and CD68 decrease expression was observed in liver tissue of (ABZ+PGE)-treated group compared with infested and ABZ-treated groups. PGE treatment indicates a significant beneficial additive antihydatic effect with a reduction of the liver side effects. The combination of albendazole and PGE treatment is more efficient and suggests its potential preventive value against Echinococcus granulosus infection.

In vivo treatment with IL-17A attenuates hydatid cyst growth and liver fibrogenesis in an experimental model of echinococcosis.

We aimed to assess the effect of exogenous Interleukin (IL)-17A in experimental model of echinococcosis. Swiss mice were inoculated intra-peritoneally with viable protoscoleces (PSCs). Then, IL-17A was administered at 100, 125 or 150 pg/mL two weeks after cystic echinococcosis (CE) induction. Cyst development and hepatic damage were macroscopically and histologically analyzed. We observed that in vivo IL-17A treatment at 100, 125, and 150 pg/mL, reduced metacestode growth by 72.3%, 93.8%, and 96.9%, respectively. Interestingly an amelioration of liver architecture was noted at 125 pg/mL without toxic effect. In this context, we showed less fibrosis reaction and reduced expression of iNOS, TNF-α, NF-κb and CD68 in hepatic parenchyma of treated mice by 125 pg/mL of IL-17A. Collectively, our results indicate an antihydatic effect and immunoprotective properties of IL-17A and suggest its potential therapeutic value against Echinococcus granulosus infection.

Immune-protective effect of echinococcosis on colitis experimental model is dependent of down regulation of TNF-α and NO production.

Hydatid disease (echinococcosis) is a chronic, endemic helminthic disease caused by the larval stage of the tapeworm, Echinococcus granulosus. This disease is endemic in many parts of the world, such as the Mediterranean area, and in particular in Algeria. Helminth parasites have developed complex strategies to modulate the immune responses of their hosts through versatile immune-regulatory mechanisms. These mechanisms may regulate immune responses associated with inflammatory diseases such as inflammatory bowel diseases (IBD). the goal of this study was to investigate the effect of Echinococcus granulosus infection on the development of dextran sulfate sodium (DSS)-induced colitis. Our results demonstrated that E. granulosus infection significantly improved the clinical symptoms and histological scores observed during DSS-induced colitis, and also maintained mucus production by goblet cells. Interestingly, this infection reduced Nitric oxide (NO) and tumor necrosis factor α (TNF-α) production and attenuated inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) expression in colonic tissues. Collectively, our data support the hygiene hypothesis and indicate that prior infection with E. granulosus can effectively protect mice from DSS-induced colitis by enhancing immune-regulatory mechanisms.

All-trans retinoic acid (ATRA) prevents lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment in aged rats.

We aimed to investigate preventive effects of All-trans retinoic acid (ATRA) on a lipopolysaccharide (LPS)-induced aged neuroinflammation model. We analyzed behavior, systemic nitric oxide (NO) production, cerebral NO synthase (NOS2) and ß-amyloid (Aß) 1-42 expression and tissue integrity in the neuroinflammation model pretreated with ATRA (150µg/ml/rat/day) for 30days. Our results showed that LPS treatment (500µg/kg/day) for 7days disturbed memory, enhanced systemic NO production, NOS2 and Aß 1-42 cerebral expression and generated an Alzheimer's disease (AD)-like neuronal degeneration. Interestingly, ATRA pretreatment prevented the LPS-induced deleterious effects. ATRA could be a potent preventive approach in AD.

Antihydatic and immunomodulatory effects of Punica granatum peel aqueous extract in a murine model of echinococcosis.

OBJECTIVE: To investigate the effect of pomegranate peel aqueous extract (PGE) on the development of secondary experimental echinococcosis and on the viability of Echinococcus granulosus protoscoleces, and the immunomodulatory properties of PGE. METHODS: Swiss mice were inoculated intraperitoneally with viable protoscoleces. Then, PGE was orally administered daily during cystic echinococcosis development. Cyst development and hepatic damage were macroscopically and histologically analyzed. The production of nitric oxide and TNF-α was assessed in plasma and the hepatic expression of iNOS, TNF-α, NF-κB and CD68 was examined. Moreover, protoscoleces were cultured and treated with different concentrations of PGE. RESULTS: It was observed that in vitro treatment of protoscoleces caused a significant decrease in viability in a PGE-dose-dependent manner. In vivo, after treatment of cystic echinococcosis infected mice with PGE, a significant decrease in nitric oxide levels (P < 0.0001) and TNF-α levels (P < 0.001) was observed. This decline was strongly related to the inhibition of cyst development (rate of hydatid cyst growth inhibition = 63.08%) and a decrease in CD68 expression in both the pericystic layer of hepatic hydatid cysts and liver tissue (P < 0.0001). A significant diminution of iNOS, TNF-α and NF-κB expression was also observed in liver tissue of treated mice (P < 0.0001). CONCLUSIONS: Our results indicate an antihydatic scolicidal effect and immunomodulatory properties of PGE, suggesting its potential therapeutic role against Echinococcus granulosus infection.

Coenzyme Q10 Supplementation Prevents Iron Overload While Improving Glycaemic Control and Antioxidant Protection in Insulin-Resistant Psammomys obesus.

This study investigated the anti-diabetic preventive activity of coenzyme Q10 (CoQ10) in a murine model of diet-induced insulin resistance (IR), Psammomys obesus (Po). IR was induced by feeding a standard laboratory diet (SD). CoQ10 oil suspension was orally administered at 10 mg/kg body weight (BW)/day along with SD for 9 months. Anthropometric parameters, namely, total body weight gain (BWG) and the relative weight of white adipose tissue (WAT) were determined. Blood glucose, insulin, quantitative insulin sensitivity check index (QUICKI), total antioxidant status (TAS), iron, malondialdehyde (MDA) and nitrite (NO2 (-)) were evaluated. NO2 (-) level was also assessed in peripheral blood mononuclear cells (PBMCs) culture supernatants. Our results show that CoQ10 supplementation significantly improved blood glucose, insulin, QUICKI, TAS, iron and MDA, but influenced neither NO2 (-) levels nor the anthropometric parameters. These findings support the hypothesis that CoQ10 would exert an anti-diabetic activity by improving both glycaemic control and antioxidant protection. The most marked effect of CoQ10 observed in this study concerns the regulation of iron levels, which may carry significant preventive importance.

Crude extract of hydatid laminated layer from Echinococcus granulosus cyst attenuates mucosal intestinal damage and inflammatory responses in Dextran Sulfate Sodium induced colitis in mice.

BACKGROUND: Inflammatory bowel disease is an immunologically mediated disease. Notably, it is less common in countries where there is a greater risk of exposure to helminths. In our study, we examined the modulatory effect of the laminated layer extracted from the cyst wall of a helminth parasite, Echinococcus granulosus, on dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: An acute colitis was induced in BALB/c mice using 2.5% w/v DSS in drinking water. The crude extract of E. granulosus laminated layer was injected intraperitoneally daily, starting 3 days before colitis induction. The Disease Activity Index was monitored daily, colon length and weight were measured and histological scores were evaluated. Nitric oxide (NO) and cytokine levels (interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10)) were assessed by enzyme-linked immunosorbent assay. In addition, the colonic expression of inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) was examined. Statistical analyses were performed by one-way analysis of variance and the survival rate was analyzed by the long rank test. RESULTS: Hydatid laminated layer pretreatment significantly improved the clinical symptoms and histological scores (*** p < 0.01) observed during DSS-induced colitis and maintained mucus production by goblet cells. Furthermore, treatment with hydatid laminated layer caused a significant decrease in NO, IFN-γ (** p < 0.01) and TNF-α production (* p < 0.05) and an increase in IL-10 production. These results were associated with localized downregulation of iNOS and NF-κB expression. CONCLUSIONS: Our results demonstrate the potent anti-inflammatory effects of hydatid laminated layer. Furthermore, preventive treatment with the laminated layer played a beneficial role in maintaining the integrity of the intestinal mucosal barrier against DSS-induced injury.