Biochemical and histologic changes in albino rats in response to charcoal powder exposure

Background. In developing and under-developed countries, charcoal production predisposes workers to charcoal dust. This is a common occurrence as workers in this field are not properly protected and as such are exposed to charcoal dust through inhalation and skin contact. Charcoal comprises many components such as polycyclic aromatic hydrocarbons (PAHs). Due to the possible health risk associated with such exposure, this study was designed to determine the effects of charcoal powder of particle size 125 µm - 150 µm on certain biomarkers in male albino rats. Albino rats were used because of their similar physiology to humans. Materials and Methods. 20 albino rats weighing between 250 g and 300 g were used for this study; they were randomly distributed in 4 groups (5 rats each) and the charcoal powder was incorporated into their feed at different percentages; control, group 1 (10 % charcoal), group 2 (30 % charcoal) and group 3 (charcoal powder bedding) for 50 days. Using standard procedures and methods, the following parameters were tested: Hematological parameters, semen parameters, liver enzymes, renal function, hormones and lung histology. Results. The results indicated a decrease in the level of liver enzymes AST (IU/L) and ALT (IU/L) in group 1, group 2 and group 3 when compared to the control with the lowest value of 48.75 IU/L and 11.50 IU/L respectively recorded in group 2. Prolactin (mIU/L) had mean values of 1.73, 1.30 and 1.83 in group 1, group 2 and group 3 respectively while the control was 2.10. Testosterone (nmol/L) had a mean value of 1.18, 0.53 and 0.25 in group 1, group 2 and group 3, respectively, while the control was 0.90 with a significant difference (P<0.05). Creatinine (µmol/L) increased in group 1 and group 2 with a slight reduction in group 3 when compared to control (1.04) with a value of 1.35, 1.40 and 1.23, respectively. Total sperm count (´105/mL) had a mean value of 58.33, 50.00 and 43.25 in group 1, group 2 and group 3, respectively, while the control was 100.50. The lung histology for the treated groups revealed infiltration of inflammatory cells and thickening of inter-alveolar walls. Conclusion. Long term exposure to charcoal powder through nasal or oral route had serious effects on rats’ health, such as kidney damages, inflammation of the lungs and decrease in fertility in males primarily due to the presence of PAHs in charcoal.

Effects of Elemental Mercury Vapor Inhalation on Arterial Blood Gases, Lung Histology, and Interleukin-1 Expression in Pulmonary Tissues of Rats

We investigated the effects of elemental mercury vapor inhalation on arterial blood gases (ABGs), lung histology, and interleukin-1 (IL-1) expression in pulmonary tissues in rats. A total of 42 Sprague Dawley rats were divided randomly into three groups. Rats in the first group were used as the control (CG). A short-term group (STG) and a long-term group (LTG) were exposed to 500 μg/m3 of mercury vapor 2 hrs/day for 21 days and 65 days, respectively. After exposure periods were completed, arterial blood samples were obtained, and ABGs were measured. Lung tissue sections were prepared for histology evaluation and immune-stained to detect IL-1 expression. There was a significant decrease in body weight in both STG (15%) and LTG (22%) compared with the CG. In the LTG, six out of 14 (43%) rats died, including two males and four females, while none of the rats in the STG died during the experiment. In both STG and LTG, a significant acid-base imbalance was characterized by a significant decrease in blood pH values and a significant increase in PCO2 values. Both PO2 and SpO2 blood values were significantly decreased in the STG and LTG, while no changes were observed in HCO3 values in all groups. Histological evaluation of lung tissues revealed severe lesions characterized by pulmonary emphysema and inflammatory cellular infiltrate. IL-1 expression in lung tissues was not significantly different between exposed rats and control subjects. These results indicate significant alterations in blood acid-base status characterized by severe respiratory acidosis with hypoxemia and no evidence of compensatory alkalosis in rats after exposure to short- and long-term elementary mercury vapor.

To study the in-vivo efficacy and safety of AYUSH polyherbal formulation among COVID-19 infected Syrian gold hamsters

The COVID-19 pandemic has infected millions of people around the world and the resulting disease burden has challenged the already stressed healthcare systems globally. Amidst the increasing morbidity rate of SARS-CoV-2, the scientific community is vigorously researching possible remedies targeted against the virus. Natural herbs have a great potency to cure infectious diseases and are vastly unexplored. The present study aims to investigate Ayurvedic herbs in a unique polyherbal formulation, NOQ19, against the SARS-CoV-2 virus in an animal model. A total of 19 female Syrian hamsters were infected with the virus cell culture through intranasal route. 4 out of 19 animals were mock controls, 5 were infection controls, 4 were treated with remdesivir and acted as positive controls and remaining 6 were treated with NOQ19. The hamsters were observed to note body weight reduction and adverse events followed by sacrifice on day 4 after inoculation with the virus. The lung pathology and viral load was studied in each hamster. Results showed a significant reduction of 78.2% in the viral load for the NOQ19 arm, as compared to the infection control. Gross examination of the lung histology of the NOQ19 arm suggested an improvement in edema and congestion compared to the infection control. Also, no adverse events were noticed in NOQ19 hamster group. Therefore, the authors propose NOQ19 formulation as a potential option to be tested further for its efficacy and efficiency against COVID-19.

Acute vaping exacerbates microbial pneumonia due to calcium (Ca2+) dysregulation

As electronic cigarette (E-cig) use, also known as “vaping”, has rapidly increased in popularity, data regarding potential pathologic effects are recently emerging. Recent associations between vaping and lung pathology have led to an increased need to scrutinize E-cigs for adverse health impacts. Our previous work (and others) has associated vaping with Ca2+-dependent cytotoxicity in cultured human airway epithelial cells. Herein, we develop a vaped e-liquid pulmonary exposure mouse model to evaluate vaping effects in vivo. Using this model, we demonstrate lung pathology through the use of preclinical measures, that is, the lung wet: dry ratio and lung histology/H&E staining. Further, we demonstrate that acute vaping increases macrophage chemotaxis, which was ascertained using flow cytometry-based techniques, and inflammatory cytokine production, via Luminex analysis, through a Ca2+-dependent mechanism. This increase in macrophage activation appears to exacerbate pulmonary pathology resulting from microbial infection. Importantly, modulating Ca2+ signaling may present a therapeutic direction for treatment against vaping-associated pulmonary inflammation.

Early treatment with a combination of two potent neutralizing antibodies improves clinical outcomes and reduces virus replication and lung inflammation in SARS-CoV-2 infected macaques

There is an urgent need for effective therapeutic interventions against SARS-CoV-2, including new variants that continue to arise. Neutralizing monoclonal antibodies have shown promise in clinical studies. We investigated the therapeutic efficacy of a combination of two potent monoclonal antibodies, C135-LS and C144-LS that carry half-life extension mutations, in the rhesus macaque model of COVID-19. Twelve young adult macaques (three groups of four animals) were inoculated intranasally and intra-tracheally with a high dose of SARS-CoV-2 and 24 hours later, treated intravenously with a high (40 mg/kg) or low (12 mg/kg) dose of the C135-LS and C144-LS antibody combination, or a control monoclonal antibody. Animals were monitored for 7 days. Compared to the control animals, animals treated with either dose of the anti-SARS-CoV-2 antibodies showed similarly improved clinical scores, lower levels of virus replication in upper and lower respiratory tract, and significantly reduced interstitial pneumonia, as measured by comprehensive lung histology. In conclusion, this study provides proof-of-concept in support of further clinical development of these monoclonal antibodies against COVID-19 during early infection.

Effect of giving probiotic supplement Lactobacillus acidophilus La-14 as an immunomodulator to maintain a respiratory system in Mus musculus

Background and Objectives: In 2020 the whole world is experiencing a pandemic condition due to infection with the SARS-CoV-2 virus which can cause the COVID-19 disease. This condition results in “Panic Buying”, because everyone tries to avoid the spread and transmission of the COVID-19 disease by doing various ways, one of which is by taking additional supplements such as vitamin C and probiotic supplements. Materials and Methods: The materials used were mice Mus musculus male DDY strain aged 1-2 months. Probiotic supplement Lactobacillus acidophilus La-14 with a viability of 1 × 108 CFU/ml. with a weight of 0.16 grams dissolved in 0.25 ml 0.9% NaCl. Vitamin C used is a commercial vitamin C tablet, weighing 0.06 grams in 0.25 ml 0.9% NaCl. Meanwhile, the feed for mice (Mus musculus) is a complete feed from Pokphand with the code BR1 CP511B. Lung histology preparations data were analysed descriptively and statistically through the test Chi square while the data on the number of lymphocytes were analysed descriptively. Results: The histological observations of lungs of Mus musculus showed that in the treatment of ML, MV, and MKA test was carried out chi square ratio between the groups that did not have lymphocyte infiltration and those that had lymphocyte infiltration showed a significant difference (p <0.05). Meanwhile, the results of the lymphocyte count showed that ML and MV treatment was higher than that of MK treatment. Conclusion: It is suggested that the administration of probiotics can stimulate and modulate the respiratory immune system.

Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective Burkholderia ΔtonB Δhcp1 live attenuated vaccines

Melioidosis, caused by Burkholderia pseudomallei (Bpm), lacks a vaccine. We identify the immune correlates of protection induced by B. mallei ΔtonB Δhcp1 (CLH001) and Bpm ΔtonB Δhcp1 (PBK001) vaccines against inhalational melioidosis. Mucosal immunization with either vaccine generates Bpm-specific IgM and IgG (IgG2b/c > IgG1 > IgG3) antibodies in sera and lungs, and lung IgA antibodies. Sera confers complement-independent bactericidal activity and macrophages opsonophagocytic uptake but is insufficient in passive transfer experiments to provide significant protection. Both vaccines elicit memory Th1 and Th17 CD4+ T-cell responses in lung and spleen after Bpm antigen-specific recall. The PBK001 vaccine is superior in generating respiratory IgA post-boost, anamnestic IgG at challenge, T-cell recall to specific antigen, and development of diverse polyfunctional memory T-cell pools. Analysis of lung histology suggests that potent polyfunctional T-cell memory and/or IL-17 signatures generated with PBK001 vaccination may be associated with moderate lung inflammation post vaccination.

Effects of Elemental Mercury Vapor Inhalation on Arterial Blood Gases, Lung Histology, and Interleukine-1 Expression in Pulmonary Tissues of Rats

We investigated the effects of elemental mercury vapor inhalation on arterial blood gases (ABG's), lung histology, and interleukin-1 (IL-1) expression in pulmonary tissues in rats. A total of 42 Sprague-Dowley rats were divided randomly into three groups. Rats in the first group were used as control (CG). A Short-Term Group (STG) and Long-Term Group (LTG) were exposed to 7.3 µl of elemental mercury vapor for 21 days and 65 days, respectively. After exposure periods were completed, arterial blood samples were obtained, and ABG’s were measured. Lung tissue sections were prepared for histology evaluation and immune-stained to detect IL-1 expression. There was a significant decrease in body weight in both STG (15%) and LTG (22%) compared to the CG. In the LTG, six rats died (43%), while none of the rats in the STG died during the experiment. In both STG and LTG, a significant acid-base imbalance was characterized by a significant decrease in blood PH values and a significant increase in PCO2 values. Both PO2 and SpO2 blood values were significantly decreased in the STG and LTG, while no changes were observed in HCO3 values in all groups. Histological evaluation of lung tissues revealed severe lesions characterized by pulmonary emphysema and inflammatory cellular infiltrate. IL-1 expression in lung tissue was not significantly different between exposed rats and control subjects. These results indicate significant alterations in blood acid-base status characterized by severe respiratory acidosis with hypoxemia and no evidence of compensatory alkalosis in rats after short and long-term elementary mercury vapor exposure.

Tim-3 is dispensable for allergic inflammation and respiratory tolerance in experimental asthma

T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) has been described as a transmembrane protein, expressed on the surface of various T cells as well as different cells of innate immunity. It has since been associated with Th1 mediated autoimmune diseases and transplantation tolerance studies, thereby indicating a possible role of this receptor in counter-regulation of Th2 immune responses. In the present study we therefore directly examined the role of Tim-3 in allergic inflammation and respiratory tolerance. First, Tim-3-/- mice and wild type controls were immunized and challenged with the model allergen ovalbumin (OVA) to induce an asthma-like phenotype. Analysis of cell numbers and distribution in the bronchoalveolar lavage (BAL) fluid as well as lung histology in H&E stained lung sections demonstrated a comparable degree of eosinophilic inflammation in both mouse strains. Th2 cytokine production in restimulated cell culture supernatants and serum IgE and IgG levels were equally increased in both genotypes. In addition, cell proliferation and the distribution of different T cell subsets were comparable. Moreover, analysis of both mouse strains in our respiratory tolerance model, where mucosal application of the model allergen before immunization, prevents the development of an asthma-like phenotype, revealed no differences in any of the parameters mentioned above. The current study demonstrates that Tim-3 is dispensable not only for the development of allergic inflammation but also for induction of respiratory tolerance in mice in an OVA-based model.

Lung Inflammation from Single and Repetitive Exposure to Glyphosate

Background: Glyphosate is an active ingredient in herbicides used in agriculture worldwide. Exposure to glyphosate has been associated with respiratory dysfunctions in agricultural workers. However, the ability of glyphosate to induce inflammation in the lung is not well studied. Therefore, we evaluated lung inflammatory response to glyphosate at agricultural relevant dose for single and repetitive exposures. Methods: Male C57BL/6 mice were intranasally exposed to glyphosate (1 μg/40 μl) for 1-day or once daily for 5-days, and 10-days. After the exposure periods, mice were euthanized to collect the bronchoalveolar lavage (BAL) fluid and lung tissue. Results: Repetitive exposure to glyphosate for 5-days and 10-days showed an increase of neutrophils in BAL fluid and eosinophil peroxidase levels in lungs, a marker for eosinophils. Leukocyte infiltration in lungs was further confirmed through lung histology. Th2 cytokines including IL-5 and IL-13 were increased in BAL fluid after 10-days of glyphosate exposure whereas IL-4 was not increased. Lung sections from all glyphosate groups showed higher expression for ICAM-1, VCAM-1, and vWF adhesion molecules. TLR-4 and TLR-2 expression was increased in lungs after repetitive exposure to glyphosate. Conclusions: We conclude that repetitive exposure to glyphosate induces migration of neutrophils and eosinophils and release of Th2 cytokines. This study, for the first time, provides evidence for the role of ICAM-1, VCAM-1 and vWF in lungs of glyphosate-treated animals.