Salivary Antiviral and Antibacterial Properties in the Encounter of SARS-CoV-2.

Due to the high mortality rate of COVID-19 and its high variability and mutability, it is essential to know the body's defense mechanisms against this virus. Saliva has numerous functions, such as digestion, protection, and antimicrobial effects. Salivary diagnostic tests for many oral and systemic diseases will be available soon because saliva is a pool of biological markers. The most important antiviral and antibacterial compounds identified in saliva include lysozyme, lactoferrin (LF), mucins, cathelicidin, salivary secretory immunoglobulin (SIgA), chromogranin A, cathelicidin, salivary agglutinin (SAG) (gp340, DMBT1), α, ß defensins, cystatin, histatins, secretory leukocyte protease inhibitor (SLPI), heat shock protein (HSP), adrenomedullin and microRNA (miRNAs). Antimicrobial peptides (AMPs) in saliva could be used in the future as models for designing effective oral microbial antibiotics. The antiviral properties of the peptides in saliva may be one of the future treatments for the COVID-19 virus. In this review, we investigate compounds with antiviral and antibacterial properties in saliva and the importance of these compounds in saliva in exposure to the COVID-19 virus. Due to the transmission route of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) into the oral cavity in the lower and upper respiratory tract, studies of salivary antiviral properties in these patients are very important. Some of the antiviral effects of saliva, especially mucin, α, ß-defensins, IgA, IgG, IgM, lysozyme, SAG, SLPI, and histatins, may play a greater role in neutralizing or eliminating COVID-19.

Thymoquinone Ameliorates Lung Inflammation and Pathological Changes Observed in Lipopolysaccharide-Induced Lung Injury.

Anti-inflammatory, antioxidant, and immunomodulatory effects of thymoquinone (TQ) have been shown. The effects of TQ on lipopolysaccharide- (LPS-) induced inflammation and pathological changes in rats' lung were investigated in this study. Four groups of rats included (1) control (saline treated); (2) LPS (treated with 1 mg/kg/day i.p. for two weeks); and (3 and 4) 5 or 10 mg/kg TQ i.p. 30 min prior to LPS administration. Total and differential WBC counts in the blood and bronchoalveolar fluid (BALF), TGF-ß1, INF-γ, PGE2, and IL-4 levels in the BALF and pathological changes of the lung were evaluated. Total WBC count and eosinophil, neutrophil, and monocyte percentage were increased, but the lymphocyte percentage was reduced in the blood and BALF. The BALF levels of PGE2, TGF-ß1, and INF-γ were also increased, but IL-4 level was reduced due to LPS administration. LPS also induced pathological insults in the lung of rats (P < 0.05 to P < 0.001 for all changes in LPS-exposed animals). Treatment with TQ showed a significant improvement in all changes induced by LPS (P < 0.05 to P < 0.05). TQ showed a protective effect on LPS-induced lung inflammation and pathological changes in rats which suggested a therapeutic potential for TQ on lung injury.

Cardiac and renal fibrosis and oxidative stress balance in lipopolysaccharide-induced inflammation in male rats.

BACKGROUND: Subclinical inflammation induced by persistent exposure to lipopolysaccharide (LPS) is found in some clinical conditions such as obesity or diabetes. This study aimed to investigate the effect of recurrent LPS exposure on inflammatory markers, oxidative stress balance and cardiac and renal fibrosis in male rats. METHODS: Male Wistar rats were divided into control and LPS-treated. LPS (10 mg/kg/week) was injected intraperitoneally. After 4 weeks, left ventricles and kidneys were homogenized and stained with hematoxylin and eosin (H&E) and Masson trichrome for histological examination. Serum levels of nitrite, interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured and total thiol, malondialdehyde (MDA), superoxide dismutase (SOD) and catalase were evaluated in the heart and kidney homogenates. RESULTS: Serum inflammatory markers were higher in LPS group than control (nitrite: 37.0 ± 2.2 vs. 25.5 ± 1.9 µmol/l; IL-6: 84 ± 3 vs. 98.0 ± 4.4 pg/ml; TNF-α: 75.5 ± 4.9 vs. 85.3 ± 4.7 pg/ml; respectively, P < 0.050). Evaluation of total thiol concentration (heart: 10.0 ± 0.9 vs. 22.5 ± 1.2; kidney: 7.0 ± 0.5 vs. 27.8 ± 3.1 nmol/g tissue, respectively), catalase (heart: 0.18 ± 0.03 vs. 0.66 ± 0.04; kidney: 0.17 ± 0.03 vs. 0.73 ± 0.03, U/g tissue, respectively) and SOD (heart: 8.01 ± 0.70 vs. 12.3 ± 0.4; kidney: 7.02 ± 0.60 vs. 12.0 ± 0.2, U/g tissue, respectively) showed lower levels in LPS-treated group compared to control; while MDA concentration in LPS group was higher than control (P < 0.05). Histopathological examination in LPS-treated group indicated infiltration of inflammatory cells and more collagen deposition in left ventricle wall and kidney compared to control group. CONCLUSION: We concluded that in clinical conditions with chronic LPS, cardiac and renal fibrosis occurs even in absence of preceding tissue injury due to imbalances in oxidative stress.

Thymoquinone Prevents Myocardial and Perivascular Fibrosis Induced by Chronic Lipopolysaccharide Exposure in Male Rats: - Thymoquinone and Cardiac Fibrosis.

OBJECTIVES: Thymoquinone (TQ) is one of the active ingredients of herbal plants such as Nigella sativa L. (NS) which has beneficial effects on the body. The beneficial effects of TQ on the cardiovascular system have reported. This study aimed to investigate the effect of TQ on cardiac fibrosis and permeability, serum and tissue concentration of inflammatory markers and oxidative stress status in chronic lipopolysaccharide exposure in male rats. METHODS: Seventy male Wistar rats were randomly divided into five groups as follows: (1) control; (2) LPS (1 mg/kg/day); (3-5) LPS + TQ with three doses of 2, 5 and 10 mg/kg (n=14 in each group). After 3 weeks, serum and cardiac levels of IL-1ß, TNF-α and nitric oxide (NO) metabolites, and cardiac levels of malondialdehyde (MDA), total thiol groups, catalase (CAT) and superoxide dismutase (SOD) activities, permeability of heart tissue (evaluated by Evans blue dye method) and myocardial fibrosis were determined, histologically. RESULTS: LPS administration induced myocardial and perivascular fibrosis and increased cardiac oxidative stress (MDA), inflammatory markers and heart permeability, while, reduced anti-oxidative enzymes (SOD and CAT) and the total thiol group. Administration of TQ significantly attenuated these observations. CONCLUSION: TQ improved myocardial and perivascular fibrosis through suppression of chronic inflammation and improving oxidative stress status and can be considered for attenuation of cardiac fibrosis in conditions with chronic low-grade inflammation.

Thymoquinone protects the rat kidneys against renal fibrosis.

Thymoquinone (TQ) is the main active ingredient of Nigella sativa seeds with various pharmacological effects. The aim of this study was to investigate the effect of TQ on renal fibrosis and permeability and oxidative stress status in lipopolysaccharide (LPS)-induced inflammation in male rats. Eighty male Wistar rats were divided into 5 groups as follow: control (received normal saline), LPS (1 mg/kg/day), and LPS+TQ (by doses of 2, 5 and 10 mg/kg/day). After three weeks, the biochemical parameters such as blood urea nitrogen (BUN) and creatinine in serum samples, oxidative stress markers including malondialdehyde (MDA), total thiol groups, superoxide dismutase (SOD) and catalase (CAT) activities in renal tissue homogenate and renal permeability (evaluated by Evan's blue dye method) were measured and renal fibrosis was evaluated, histologically using Masson's trichrome staining. LPS administration induced renal fibrosis (1.49 ± 0.08 vs. 7.15 ± 0.18%) and significantly increased renal permeability (6.03 ± 1.05 vs. 13.5 ± 1.04 µg evans blue(EB)/g tissue), serum BUN and creatinine levels and oxidative stress marker (MDA) (P < 0.05), while, it reduced anti-oxidative markers including total thiol group, SOD and CAT activities (P < 0.05). Administration of TQ significantly improved these alterations which were dose-dependent in oxidative stress markers, renal permeability (TQ 2, 5 and 10 mg/kg: 10.7 ± 0.3, 9.2 ± 1.4 and 11.5 ± 0.6 µg EB/g tissue; respectively) and fibrosis (TQ 2, 5 and 10 mg/kg: 6.09 ± 0.7, 4.26 ± 0.14 and 2.52 ± 0.08%; respectively). In conclusion, administration of TQ reduced renal fibrosis and permeability and improved oxidative stress status. Thus, TQ can be considered in conditions accompanied with chronic inflammation at least as a part of treatment strategy.

The effects of thymoquinone on hippocampal cytokine level, brain oxidative stress status and memory deficits induced by lipopolysaccharide in rats.

OBJECTIVE: The study objective was to determine the protective effects of thymoquinone (TQ) on brain tissues oxidative stress status, hippocampal cytokine level, and learning and memory deficits induced by lipopolysaccharide (LPS) in rats. METHODS: Animals were randomly divided into the following groups and treated: (1) Control (saline), (2) LPS (1mg/kg i.p.), (3-5) 2, 5 or 10mg/kg TQ extract 30min before LPS injection. The treatment was started since two weeks before the behavioral experiments and continued during the behavioral tests (LPS injected 2h before each behavioral experiment). Finally, the brains were removed for biochemical assessments. RESULTS: Morris water maze (MWM) test results showed that LPS increased escape latency compared to control group whereas TQ decreased them vs. LPS group. In passive avoidance (PA) test, LPS reduced the latency to enter the dark compartment vs. control group, while TQ treatment attenuated this effect of LPS. Additionally, LPS increased interleukin-6 (IL-6) and tumor necrosis alpha (TNF-α) in the hippocampal tissues. It also elevated malondialdehyde (MDA) and nitric oxide (NO) metabolites and decreased thiol content, superoxide dismutase (SOD) and catalase (CAT) in both hippocampus and cortex vs. control group, while TQ decreased IL-6, TNF-α, MDA and NO metabolites and increased thiol content, SOD and CAT compared to LPS group. CONCLUSION: Findings of current study indicated that TQ improved LPS-induced learning and memory impairments induced by LPS in rats by attenuating the hippocampal cytokine levels and brain tissues oxidative damage.

Thymoquinone restores liver fibrosis and improves oxidative stress status in a lipopolysaccharide-induced inflammation model in rats.

OBJECTIVE: Liver fibrosis is the primary sign of chronic liver injury induced by various causes. Thymoquinone (TQ) is the major ingredient of Nigella sativa with several beneficial effects on the body. In the present study, we aimed to investigate the effect of TQ on liver fibrosis in a lipopolysaccharide (LPS)-induced inflammation in male rats. MATERIALS AND METHODS: Fifty male Wistar rats were randomly divided into five groups (n=10 in each group) as follow: (1) control; (2) LPS (1 mg/kg/day; i.p); (3) LPS+TQ 2 mg/kg/day (i.p) (LPs+TQ2); (4) LPS+TQ 5 mg/kg/day (LPS+TQ5); (5) LPS+ TQ 10 mg/kg/day (LPS+ TQ10). After three weeks, blood samples were taken for evaluation of liver function tests. Then, the livers were harvested for histological evaluation of fibrosis and collagen content and measurement of oxidative stress markers including malondialdehyde (MDA), total thiol groups, superoxide dismutase (SOD) and catalase activity in tissue homogenates. RESULTS: LPS group showed higher levels of fibrosis and collagen content stained by Masson's trichrome in liver tissue with impaired liver function test and increased oxidative stress markers (p<0.05). Treatment by TQ restored liver fibrosis, improved liver function tests and increased the levels of anti-oxidative enzymes (SOD and catalase), while reduced MDA concentration (p<0.05). CONCLUSION: Treatment by TQ restores inflammation-induced liver fibrosis possibly through affecting oxidative stress status. It seems that administration of TQ can be considered as a part of liver fibrosis management.