Protective effect of dexamethasone against paraquat-triggered toxicity in A549 cells through inhibiting inflammation, apoptosis and TGF-ß1/Smad3 pathway.

Dexamethasone is a glucocorticoid that is used for the treatment of interstitial pneumonia and pulmonary fibrosis as it possesses anti-inflammatory and anti-fibrosis properties. In the current study, A549 cells were exposed to paraquat, dexamethasone, or both of them, to investigate the potential effect of dexamethasone against paraquat-triggered poisoning in A549 cells. The inflammatory response was evaluated by measuring tumor necrosis factor-α, interleukin-1ß, and interleukin-6 while the degree of fibrosis was assessed by detecting collagen I and fibronectin using enzyme-linked immunosorbent assay. Western blotting was used to assess the protein expression of apoptotic proteins as well as transforming growth factor-ß1, Smad 3 and phospho-Smad 3. DNA ladder assay was performed to estimate DNA damage in different groups of the alveolar epithelial cells. Dexamethasone protected against paraquat-induced inflammatory response as shown by the significantly reduced levels of the pro-inflammatory cytokines and it also alleviated paraquat-provoked fibrosis as it substantially diminished collagen I and fibronectin levels. Moreover, dexamethasone remarkably decreased the relative expression levels of transforming growth factor-ß1 and phospho-Smad3 that were upregulated upon PQ treatment. Dexamethasone also protected against paraquat-induced genotoxicity and apoptosis. In conclusion, dexamethasone may protect against paraquat-induced inflammation, fibrosis, genotoxicity, and apoptosis via modulating TGF-ß1/Smad 3 signaling pathway.

Protective effect of Moringa oleifera Lam. leaf extract against oxidative stress, inflammation, depression, and apoptosis in a mouse model of hepatic encephalopathy.

The present study aimed to assess the antioxidative, anti-inflammatory, antiapoptotic, and anti-depression impacts of Moringa oleifera Lam. leaf ethanolic extract (MOLE) in the hippocampus and cerebral cortex of CCl4-induced hepatic encephalopathy mouse model. High-performance liquid chromatography was used to detect marker compounds: rutin and ß-sitosterol. Animals were divided into four groups: vehicle group, CCl4-treated group, MOLE-treated group, and (CCl4 + MOLE) group treated with MOLE for 14 days before CCl4-induced neurotoxicity. MOLE decreased alanine aminotransferase, aspartate aminotransferase, corticosterone, and ammonia levels in serum and improved the antioxidant status of CCl4-treated mice in the hippocampus and cerebral cortex. It reduced the expression of toll-like receptor 4 (TLR4), TLR2, myeloid differentiation primary response 88 (MYD88), and nuclear factor-kappa B (NF-κB) genes and the protein levels of the pro-inflammatory cytokines. MOLE also attenuated apoptosis, as revealed by the reduced expression of caspase3, and prevented histological deterioration. Furthermore, MOLE attenuated CCl4-induced anxiety and depression-like behavioral changes. Collectively, MOLE modulates neuroinflammation, oxidative stress, TLR4/2-MyD88/NF-κB signaling, and apoptosis in the hippocampus and cerebral cortex of the hepatic encephalopathy experimental model.

The ameliorative effect of kaempferol against CdCl2- mediated renal damage entails activation of Nrf2 and inhibition of NF-kB.

This study evaluated the nephroprotective effect of kaempferol against cadmium chloride (CdCl2) -induced nephropathy in rats. It also investigated if activation of Nrf2 is a common mechanism of action. Adult male rats ((150 ± 15 g) were divided into 4 groups (n = 8/each) as a control (1% DMSO, orally), control + kaempferol (200 mg/kg, orally), CdCl2 (50 mg/l in drinking water), and CdCl2 + kaempferol (200 mg/kg)-treated rats. All treatments were conducted for 8 weeks. Kaempferol significantly attenuated CdCl2-induced weight loss, reduction in kidney weights, and the injury in the glomeruli, proximal tubules, and distal tubules in the treated rats. It also significantly lowered serum levels of urea and creatinine, increased urine output and urinary creatinine levels and clearance but reduced urinary levels of albumin urinary albumin exertion (UAER), and urinary albumin/creatinine ratio (UACR) in these rats. In parallel, kaempferol downregulated renal levels of cleaved caspase-3 and Bax and unregulated those of Bcl2. In the kidney tissues of the control animals and CdCl2 rats, kaempferol significantly attenuated oxidative stress, inflammation and significantly boosted levels of manganese superoxide dismutase and glutathione. Also, and in both groups, kaempferol suppressed the nuclear levels of NF-κB p65, downregulated Keap1, and stimulated the nuclear activation and protein levels of Nrf2. In conclusion, kaempferol is a potential therapeutic drug to prevent CdCl2-induced nephropathy due to its anti-inflammatory and anti-oxidant effects mediated by suppressing NF- NF-κB p65 and transactivating Nrf2.

Environmental Risk Factors in Patients with Noninvasive Fungal Sinusitis.

Objective. The aim of our study was to try to determine the possible environmental risk factors for noninvasive fungal sinusitis in Egyptian patients. Methods. This is a prospective epidemiological case control study on the environmental risk factors of noninvasive fungal sinusitis. It included 60 patients and 100 age and sex matched controls. Results. There was a statistically significant relation between apartment floor, surface area, exposure to dust, exposure to cockroaches, poor air conditioning, and fungal sinusitis. Yet, no statistical significance was found between allergy related occupations, exposure to animals or plants, although their percentages were higher among cases, smoking, and urban or rural residence. Conclusion. We suggest that for patients with noninvasive fungal sinusitis a change in their living environment must be implied with better exposure to sunlight, larger well ventilated homes, proper cleaning of dust and cockroach extermination, and if possible the judicious use of air conditioners.