Suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ivermectin is a US Food and Drug Administration (FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties. Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries, its potential therapeutic effect on pulmonary fibrosis (PF) has not been investigated. This study aimed to explore the ability of ivermectin (0.6 mg/kg) to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model. This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF. The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury, as manifested by the reduced infiltration of inflammatory cells, as well as decreased the inflammation and fibrosis scores. Intriguingly, ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-‍β1 (TGF-‍β1) and fibronectin protein expression, highlighting its anti-fibrotic activity. This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain (NOD)‍-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), with a subsequent decline in the interleukin‍-‍1β (IL‍-‍1β) level. In addition, ivermectin inhibited the expression of intracellular nuclear factor-‍κB (NF‍-‍κB) and hypoxia‑inducible factor‑1α (HIF‍-‍1α) proteins along with lowering the oxidative stress and apoptotic markers. Altogether, this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin. These beneficial effects were mediated, at least partly, via the downregulation of TGF-‍β1 and fibronectin, as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1α and NF-‍κB.

Moringa oleifera leaf ethanol extract ameliorates lead-induced hepato-nephrotoxicity in rabbits

Objective: To evaluate the effect of Moringa oleifera leaf ethanol extract as an adjunct treatment on lead acetate induced hepato-nephrotoxicity in rabbits. Methods: Thirty-six male New Zealand White rabbits were assigned into two main groups. The first group (14 rabbits) served as normal control. The secondgroup (22 rabbits) was administered orally with lead acetate at a dose of 40 mg/kg/day, 5 days/week for 8 weeks. At the 4th and the 8th week of treatment, 6 animals (3 animals at each period) of the second group were sacrificed while the remaining animals (16 rabbits) were assigned randomly into 2 subgroups (8 rabbits each): treated and non-treated. The first subgroup was orally given 1 mL phosphate-buffered saline for further 4 weeks while the second subgroup was administered orally with Moringa oleifera leaf ethanol extract at a dose of 400 mg/kg/day for the same period. Blood samples were collected to determine hematological and serum biochemical indices. Tissue specimens were collected from the liver and kidney for evaluation of the oxidant/antioxidant markers and for histopathological examinations. Results: Lead acetate exposure decreased the mean body weight gain, hematocrit, hemoglobin, mean corpuscular volume, and lymphocytes count. Moreover, it markedly increased counts of monocytes and platelets, serum enzyme activity, levels of creatinine, total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Malondialdehyde level was markedly increased while the reduced glutathione content was significantly decreased in liver tissue of lead intoxicated-rabbits. Histopathological alterations were also noticed in the liver and kidney of lead intoxicated rabbits. Moringa oleifera leaf ethanol extract significantly improved hematological and serum biochemical parameters and histopathological structure of the liver and kidney. Conclusions: Moringa oleifera leaf ethanol extract ameliorates hemato-biochemical and histopathological alterations caused by lead acetate and improveshepatic and renal functions.

Modulating effect of peppermint and eucalyptus oils in infectious bursal disease immunocompromised chickens

The immunomodulatory effect of peppermint and eucalyptus essential oils in broiler chickens immunoconmpromised by either infection or vaccination with infectious bursal disease virus [IBDV] was investigated. No significant difference in HI titers was observed in volatile oils treated group over their untreated one at any interval. However, the protection percentage reached 35% in treated group and was 25% in untreated one as Compared with 0% in unvaccinated control group when challenged with velogenic viscerotropic Newcastle disease virus [vvNDV]. Significant increase in Bursa / body weight ratios was observed between IBDV vaccinated treated group as compared with untreated one at 3 and 10 days post-vaccination [PV]. In addition, significant increase was observed between IBDV infected treated birds versus infected untreated group at 3 days Post-infection [PI]. These findings indicate that treatment with volatile oil ameliorated the immunocompromised effects of IBDV vaccine or infection on immune system of treated birds. The positive effect of volatile oils on cell mediated immunity of treated birds revealed significant increase in phagocytic%, lysozyme and nitric oxide activities at 14 and 28 days of age in IBDV vaccinated and treated birds as compared with IBDV vaccinated and untreated birds. Moreover; the phagocytic index was higher in IBDV infected and treated birds over non treated ones at 42 days of age. Histomorphological examination of the major immune organs clarified lymphocytic necrosis and depletion, hyperplasia of reticuloendothelial cells, vacuolations of lymphoid follicles, interfollicular lyinphocytic cells infiltration and interfollicular connective tissue proliferation of bursa of Fabricius [B,F]. Lymphocytic depletion and hyperplasia of reticular cells of spleen. Lymphocytic necrosis, depletion, focal hemorrhage of thymus glands. Necrosis and depletion of caecal tonsils. The sum lesion scores were 0, 0, 2 and 1, 1, 5 in volatile oils treated and untreated chickens at 3, 7 and 10 days PV respectively. While the sum lesion scores reached 21, 23, 14 and 21, 23, 20 in volatile oils treated and untreated chickens at 3, 7 and 10 days PI respectively. On the other hand there was lymphoblast activation reached 1 score in BF in volatile oils treated group only at 3 and 7 days PV. No histopathological changes all over the experimental period could be detected in blank control group. In conclusion our study reveals that eucalyptus and peppermint oils have a potent immunomodulatory effects and are able to evoke the immune response in IBDV vaccinated or infected chickens

Genetical and pathological study on effect of fenugreek on kinetics of the mice tissues

In the present investigation, the effects of fenugreek [T foenum graecum] administration on the liver and ovarian activity were studied. Seventy two Swiss albino female mice were orally administrated with different doses of fenugreek oil for 10 days. The mode and magnitude of effect was found to be depending on the dose of fenugreek oil and type of tissue. Administration of fenugreek oil at 0.1 and 0.15 ml/ mouse increased the total number of cumulus-oocyte complexes- [COCs] as well as improved their quality. Cytogenetically, fenugreek oil was able to stimulate the oocytes collected from treated mice at different doses to progress in meiosis. Half of the oocytes number collected from female mice treated with fenugreek oil were arrived at GVBD and M I stages. However, most oocytes collected from untreated female mice were still in GV stage. Levels of nucleic acids content in all groups did not significantly change neither in the DNA nor RNA in ovarian- or liver-tissues. Histopathological examination of the ovaries collected from untreated mice as well as from mice treated with 0.05 ml/ mouse of fenugreek oil showed no histopathological alterations. However, ovaries of mice treated with 0.1 or 0.15 ml/ mouse of fenugreek oil showed numerous mature ovarian follicles as well as multiple corpora lutea. According to the available literatures, this is the first study that suggests significant stimulating effects of fenugreek oil on the ovarian activity in mice

Assessment of the activity of provitamin A against hepatocarcinogenesis in rats

The present work was performed to study the influence of chemoprotective and preventive activity of dietary carrot which was consumed daily on hepatocarcinogenesis induced by Dibutylnitrosamine [DBN] in male albino rats. Sixty six adult male albino rats [Sprague Dawley Strain] were randomly allocated in groups of eleven rats fed continuously for 60 days on six diets. The first three groups were served as control and put on the following diets throughout the experimental period, [GI] commercial diet; [G2] commercial diet with 50g of fresh carrot daily; [G3] commercial diet and treated with Dibutylnitrosamine [DBN] in drinking water as hepatocarcinogenie agent. The other experimental groups were fed on commercial diet +50g of fresh carrot, 30 days before [G4] or after treatment with DBN [G5] respectively, while G6 received commercial diet +50 g of fresh carrot daily and treated at the same time with DBN throughout the experimental period, 60 days. Fasting blood samples were taken on the day 60 for the determination of antioxidative state by measuring reduced glutathione [GSH]; complete blood picture [CBC] and blood indices; serum and liver malondialdehydc [lipid peroxidations marker]; liver GSH; serum AST, ALT, ALP, LDH, GOT, total and direct bilirubin; serum total protein and albumin; and pathologic evaluations were made. Fresh carrot administration revealed a protective and preventive effects on the rats hepatocyte treated with DBN which was reflected by the significant reduction in the liver function tests [AST, ALT, ALP, GOT, LDH and total bilirubin], while no significant improvement in either total protein or albumin could be detected. This reduction is ordered among the different treated groups as following G5, G6 and G4. The oxidative state was determined by measuring liver and whole blood GSH, exhibiting significant increase in blood GSH in contrast to significant reduction in liver GSH. While liver and serum MDA concentration as lipid peroxidation index, showed significant reduction in serum and liver MDA. Histopathologically, liver of rats fed carrot before, during or after hepatocarcinogensis, showed highly improvement on preneoplastic lesions, less fibrosis and oval cells development than positive control, but in different degree of lesions. It was concluded that, carrot consumption was very effective in preventing hepatocarcinogensis, when it is administrated daily after short exposure to hepatocarcinogen, while before or during the earcinogenesis carrot intake may have mild improvement effect on hepatocarcinogenesis which was revealed by decrease in the severity of illness

Efficacy and pathogenicity of three live infectious bursal disease vaccines [intermediate plus strains] in commercial native chickens breed in Egypt

In this study, three of live intermediate plus IBDV vaccines [A, B, and C] which are commonly used in Egypt were selected and their pathogenicity and efficacy were investigated. Groups of native breed chicks were vaccinated at 14 days of age with each vaccine by eye drop route and in drinking water then challenged with virulent field IBDV 14 days post vaccination [PV]. The efficacy and pathogenicity of each vaccine were evaluated based on clinical signs, mortalities, gross lesion, Bursa/ body weight ratio [BF/BW], and histopathological lesions of the bursa. It was found that these vaccines are efficient as they conferred 100% protection in all vaccinated and challenged groups compared with 20% mortality in unvaccinated challenged group. However, they did not prevent bursal atrophy or histological lesions. The bursal atrophy was observed at 7days PV in groups vaccinated with vaccine [A] while it was observed at 10 days PV in groups vaccinated with vaccines [B] and [C]. Vaccine [A] was proved to be more invasive compared with vaccines [B] and [C] as evidenced by higher bursal lesion scores and lower relative BF/BW ratios at certain intervals PV. When vaccine B and C were given in drinking water, moderate to severe bursal changes were observed. Meanwhile, when these vaccines [B and C] were given by eye drop route, mild to moderate changes in the bursa were observed indicating that vaccination by eye drop route would be better than in drinking water. It would be concluded that, all studied vaccines are efficacious and they vary in invasiveness and pathogenicity. Vaccines [B] and [C] are less pathogenic than vaccines [A] and the vaccination by eye drop route will result in less severe bursal lesions and better immune response than in drinking water

Bees honey abolishes the physiological disorders induced by some synthetic food colourant additives administered to young male albino rats

This work aimed to study the physiological changes in body weight, blood picture, thyroid hormones [T3 and T4] and liver functions as well as to examine the histochemical and histopathological changes in the liver of young male rats after receiving one of two colors additives mixture commonly used in local food factories in the Egyptian market [colour I, tartrazine and carmoisine and colour II, brilliant blue, sunset yellow, tartrazine and carmoisine] at a dose level of 0.3 g% in drinking water for 8 weeks. This work was also extended to study the possible protective role of a regular daily intake of bees honey [3.3 mg/kg b.wt.] against the disturbances induced by these colours additives. In conclusion, the tested synthetic food colours additives induced physiological disturbances in rats. On the other hand, the administration of bees honey plays an important protective role against the deleterious effects of the colours additives. However, even recent studies of the carcinogenic and other adverse properties of these compounds have failed to provide a basis for the confident prediction of the physiological specifications; hence, there is still a necessity of their metabolic and toxicological properties