Impact of Oral Probiotics in Amelioration of Immunological and Inflammatory Responses on Experimentally Induced Acute Diverticulitis.

Acute diverticulitis is inflammation of a colon diverticulum; it represents a major cause of morbidity and mortality. The alteration of gut microbiota contributes to the promotion of inflammation and the development of acute diverticulitis disease. Probiotics can modify the gut microbiota, so they are considered a promising option for managing diverticulitis disease. This study aimed to investigate the potential protective effect of probiotics, alone or in combination with amoxicillin, on the experimentally induced model of acute diverticulitis disease. Forty-two rats were divided into seven groups as follows: control group: received water and food only; DSS group: received 3% dextran sulfate sodium (DSS) daily for 7 days; LPS group: injected with lipopolysaccharide (LPS) enema at the dose of (4 mg/kg); probiotics group: treated with probiotics (Lactobacillus acidophilus and Bifidobacterium lactis) each of which (4 × 108 CFU suspended in 2 ml distilled water) orally for 7 days; DSS/LPS group: received DSS and LPS; DSS/LPS treated with probiotics group; DSS/LPS treated with probiotics and amoxicillin group. The results revealed that both treatments (probiotics and probiotics-amoxicillin) attenuated DSS/LPS-induced diverticulitis, by restoring the colonic antioxidant status, ameliorating inflammation (significantly reduced TNF-α, interleukins, interferon-γ, myeloperoxidase activity, and C-reactive protein), decreasing apoptosis (through downregulating caspase-3), and reduction of the colon aerobic bacterial count. These probiotic strains were effective in preventing the development of the experimentally induced acute diverticulitis through the anti-inflammatory and immunomodulatory effects and have affected gut microbiota, so they can be considered a potential option in treating acute diverticulitis disease.

Protective effects of amoxicillin and probiotics on colon disorders in an experimental model of acute diverticulitis disease.

Acute diverticulitis disease is associated with inflammation and infection in the colon diverticula and may lead to severe morbidity. This study aimed to evaluate and compare the protective effects of amoxicillin antibiotic, either alone or in combination with probiotics (Lactobacillus acidophilus and Bifidobacterium lactis), in a rat model of acute diverticulitis disease. Acute diverticulitis was induced, in albino rats, by adding 3% weight/volume of dextran sulfate sodium (DSS) to the rats' drinking water; daily for 7 days, in addition to injecting lipopolysaccharide (LPS) enema (4 mg/kg). The impact of treatments was assessed by measuring the physiological and immunological parameters and evaluating colon macroscopic and microscopic lesions. The results showed that both treatments (especially probiotics with amoxicillin) alleviated the adverse effects of DSS and LPS. This was obvious through the modulation of the rats' body weight and the colon weight-to-length ratio. Also, there was a significant (p < 0.001) decrease in the colon macroscopic lesion score. The pro-inflammatory cytokines [(TNF)-α, (IL)-1ß, (IFN)-γ, and (IL)-18]; in the colon tissue; were significantly (p < 0.001) decreased. Also, both treatments significantly ameliorated the elevation of myeloperoxidase activity and C-reactive protein levels, in addition to improving the histopathological alterations in the colon tissue. In conclusion, amoxicillin and probiotics-amoxicillin were effective in preventing the development of experimentally induced acute diverticulitis, through their anti-inflammatory and immunomodulatory effects. Furthermore, this study has explored the role of probiotics in preventing DSS/LPS-induced acute diverticulitis, so it can be applied as a promising treatment option for acute diverticulitis disease.

Ameliorative effect of bone marrow-derived mesenchymal stem cells on burn-induced hepatic and metabolic derangements in rats.

AIMS: The current study aims to investigate the therapeutic potential of bone marrow-derived mesenchymal stem cells (MSCs) as a solo therapy in ameliorating both skin lesions and liver injury induced by cutaneous severe burn injury (SBI) in rats. MAIN METHODS: In anesthetized male adult Wistar albino rats, 30 % total burn surface area and established hepatic injury was achieved via direct contact of each experimental animal's dorsum with heated metal rod (100 °C) for 10 s. On the next day following burn, human MSCs or mouse MSCs was administered locally around the burn site and intraperitonially (0.5 × 106 cells/rat for each route) and outcomes were investigated at 4 and 14 days following burn induction. KEY FINDINGS: Both types of MSCs significantly improved skin and liver histology, decreased liver enzymes, and ameliorated oxidative stress in hepatocytes of SBI-rats. Further, SBI-induced rises in hepatic apoptotic marker (caspase-3, Bax) and serum inflammatory markers (TNF-α, IL-1ß, and IL-6) were reduced following either human or mouse MSC administration. In addition, MSCs augmented insulin receptor substrate-1, phosphorylated protein kinase-B (phospho-Akt), while alleviating serum glucose levels in SBI-rats. These previous effects persisted even at the 14-day time point. SIGNIFICANCE: Following single administration, bone marrow-derived MSCs is capable of counteracting SBI-induced skin lesions as well as related hepatic complications, specifically via mitigating postburn hyperglycemia and hyperinflammation.

The possible neurobehavioral protective effects of natural antioxidant against phototoxicity attenuation of antimicrobial quinolone group in rats.

The fluoroquinolones absorb light in the 320 to 330 nm ultraviolet A (UV-A) wavelength and produce reactive oxygen species (ROS) such as superoxide anion, hydroxyl radical, and hydrogen peroxide; thus, the photodynamic generation of ROS may be the basis of phototoxicity of quinolones in human beings and animals. This study aimed to evaluate the damaging effects of UV-A radiation at different periods of exposure on rats' brains administered with ciprofloxacin. Ciprofloxacin administration in UV-A exposed animals exaggerated the brain-oxidative stress biomarkers and decreased the locomotor activity. Exposure of rats to UV-A for 60 minutes induced a significant increase of malondialdehyde (MDA), myeloperoxidase (MPO), and a decrease in the values of superoxide dismutase (SOD), glutathione (GSH) compared to a normal one; these changes were UV-A exposure time-dependent. However, the administration of vitamin C to the UV-60-treated group decreased the values of MDA, MPO, and shifted the values of SOD, GSH toward the normal values. Vitamin C, probably due to its strong antioxidant properties, could improve and partially counteract the toxic effect of UV-A on oxidative stress parameters and prevent the damage in rat's brain tissues.

Mesenchymal stem cells therapeutic potential alleviate lipopolysaccharide-induced acute lung injury in rat model.

Inhalation of bacterial endotoxin induces an acute inflammation in the lower respiratory tract. The current study examined the therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) in lipopolysaccharide (LPS)-induced pulmonary congestion in rats as compared with dexamethasone (Dexa) and sodium bicarbonate (NaHCO3 ). LPS (20 µL of LPS of Escherichia coli in each nostril for two consecutive days) induced lung injury as marked by an elevation of number of inflammatory cells especially neutrophils, increased total protein levels, elevation of lipid peroxidation, and reduction of reduced glutathione in bronchoalveolar lavage along with the reduction of reduced glutathione. These deleterious effects were hampered after treatment with BM-MSCs (1 × 106 cells/rat) once before acute lung injury (ALI) induction with LPS to an even better extent than Dexa (2 mg/kg once, ip) and NaHCO3 (10-15 mL/day for two consecutive days). In summary, BM-MSCs have the ability to suppress the endotoxin-induced systemic inflammatory response and could prove to be a novel approach to therapy for ALI in rats.

Neuroinflammatory reactions in sickness behavior induced by bacterial infection: Protective effect of minocycline.

The neurological changes elicited by bacterial infection are called sickness behavior. Minocycline (MIN) is neuroprotective with a remarkable brain tissue penetration. MIN was orally administered at a dose 90 mg/kg for 3 days, whereas Escherichia coli was given as a single intraperitoneal injection (0.2 mL of 24 h growth) on the third day. After 24 h of bacterial infection, behavioral tests namely open field and forced swimming were carried out, then animals were decapitated. Rats infected with E. coli displayed reduced struggling time in forced swimming test, as well as, exploration and locomotion in open field test with reduction in neurotransmitters (norepinephrine, dopamine, and serotonin) versus elevation in the inflammatory (tumor necrosis factor-alpha, interferon-gamma) and oxidative stress (thiobarbituric acid reactive substance, reduced glutathione) biomarkers. Inflammatory infiltrates of nuclear cells were observed in brains of infected rats. MIN administration prevented the deleterious effects of E. coli infection, thus protects against sickness behavior possibly via defending from neuroinflammation.

Concurrent administration effect of antibiotic and anti-inflammatory drugs on the immunotoxicity of bacterial endotoxins.

Pseudomonas aeruginosa (P. aeruginosa) is a gram-negative bacterium that causes a variety of diseases in compromised hosts. Bacterial endotoxins such as lipopolysaccharide (LPS) are the major outer surface membrane components that are present in almost all gram-negative bacteria and act as extremely strong stimulators of innate immunity and inflammation of the airway. This study was undertaken to determine the effect of combined administration of Gentamicin (GENT) as an antibiotic and Dexamethasone (DEXA) as an anti-inflammatory drug on some immunological and histological parameters. After determination of LD50 of P. aeruginosa, mice groups were injected with DEXA, GENT and lipopolysaccharide alone or in combination. Lipopolysaccharide single injection caused a significant increase of total leukocyte count, lymphocytes, neutrophils and levels of IgM and IgG. DEXA induced an increase of neutrophilia and lymphopenia. Immunological examination demonstrated that combined treatment has a significant effect of decreasing lymphocytes and IgG levels than single treatment does. Histological examination demonstrated that the inflammation of thymus, spleen, lymph node and liver decreases in mice that received combined treatment than those that received individual treatment. Concurrent administration of DEXA and GENT has a great effect on protecting organs against damage in case of endotoxemia.

The neuroprotective effect of mesenchymal stem cells on an experimentally induced model for multiple sclerosis in mice.

Multiple sclerosis (MS) is a chronic autoimmune demyelinating neurodegenerative central nervous system disorder. The aim of the present study was to investigate the prophylactic effect exerted by the one-time intraperitoneal injection of mesenchymal stem cells (MSCs) 1 × 106 and 14-day intraperitoneal injection of methylprednisolone (MP) 40 mg/kg in an experimental autoimmune encephalomyelitis (EAE). EAE was induced by intradermal injection of rat spinal cord homogenate with complete Freund's adjuvant in Swiss mice. Results of MSCs and MP-treated mice showed a significantly milder disease and fewer clinical scores compared to control mice. They suppressed tumor necrosis factor-alpha and myeloperoxidase and increased interleukin 10, whereas thiobarbituric acid reactive substances and nitric oxide brain contents were reduced to comparable levels between treatment groups. Brain content of GSH was significantly higher in MSCs-treated mice than control mice. It is evident that MSCs have relevant prophylactic effect in an animal model of MS and might represent a valuable tool for stem cell based therapy in MS.

Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats.

Cerebrolysin (CBL), a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF), is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ) on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i) vehicle- (ii) CBL- and (iii) STZ diabetic-control as well as (iv) STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%), which were associated by weight loss, elevated tumor necrosis factor (TNF)-α and decreased insulin growth factor (IGF)-1ß in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp)-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU), glycine, serotonin (5-HT) and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-α and IGF-1ß, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti-inflammatory, antioxidant and antiapototic effects.