Empagliflozin inhibits autophagy and mitigates airway inflammation and remodelling in mice with ovalbumin-induced allergic asthma.

Empagliflozin, a selective inhibitor of Na+-glucose cotransporter-2, has been reported to exert anti-inflammatory and anti-fibrotic effects in addition to autophagy modulation. Addressing the role of autophagy in allergic asthma revealed controversial results. The potential effect of empagliflozin treatment on airway inflammation and remodelling as well as autophagy modulation in a murine model of allergic asthma was investigated. Over a 7-week period, male BALB/c mice were sensitized and challenged by intraperitoneal injection and inhalation of ovalbumin, respectively. Animals were treated with empagliflozin (10 mg/kg; orally) and/or rapamycin (an autophagy inducer; 4 mg/kg; intraperitoneally) before every challenge. Methacholine-induced airway hyperresponsiveness was evaluated one day after the last challenge. After euthanasia, serum, bronchoalveolar lavage fluid, and lung tissues were collected for biochemical, histopathological, and immunohistochemical assessment. Results revealed that empagliflozin decreased airway hyperresponsiveness, serum ovalbumin-specific immunoglobulin E, and bronchoalveolar lavage total and differential leukocytic counts. Levels of inflammatory and profibrotic cytokines (IL-4, IL-5, IL-13, IL-17, and transforming growth factor-ß1) were all inhibited. Moreover, empagliflozin preserved pulmonary microscopic architecture and alleviated bronchiolar epithelial thickening, goblet cell hyperplasia, fibrosis and smooth muscle hypertrophy. These effects were associated with inhibition of ovalbumin-activated autophagic flux, as demonstrated by decreased LC3B expression and LC3BII/I ratio, as well as increased P62 expression. However, the therapeutic potential of empagliflozin was inhibited when rapamycin was co-administered. In conclusion, this study demonstrates that empagliflozin has immunomodulatory, anti-inflammatory, and anti-remodelling properties in ovalbumin-induced allergic asthma and suggests that autophagic flux inhibition may play a role in empagliflozin's anti-asthmatic effects.

Cerium oxide nanoparticles could ameliorate behavioral and neurochemical impairments in 6-hydroxydopamine induced Parkinson's disease in rats.

BACKGROUND: Cerium oxide nanoparticles (CeO2NPs) showed promising effects in neurodegenerative diseases including some animal models of Parkinsonism. However, the implication of CeO2NPs in 6-hydroxydopamine (6-OHDA) induced Parkinsonism remains to be investigated. AIM: This study was designed to assess whether CeO2NPs treatment could alleviate neurobehavioral and neurobiochemical deficits in 6-OHDA induced neurotoxicity in rats. MATERIAL AND METHODS: 50 rats received left intrastriatal (IS) injection of either saline (control, n = 10) or 6-OHDA (n = 40). At the third week post-lesion, motor dysfunction was verified using neurobehavioral tests. Then diseased rats received intraperitoneal injection of 0.1, 0.5 or 1 mg/kg of CeO2NPs or vehicle (10 rats each) for 3 weeks. Rats were subjected to behavioral assessments and then sacrificed for biochemical analyses of the striatum. Striatal dopamine levels, oxidative stress markers including total antioxidant capacity (TAC) and malondialdehyde (MDA), and caspase 3 activity as an apoptotic marker were assessed. RESULTS: Different doses of CeO2NPs variably improved motor dysfunctions induced by 6-OHDA injection in open field, Rota Rod and stepping tests. In addition, the neurobiochemical derangements were almost reversed by the 0.5 mg/kg dose of CeO2NPs, while 0.1 mg/kg dose was not sufficient to alter biochemical measurements in the striatum. Administration of 1 mg/kg of CeO2NPs partially ameliorated striatal dopamine and decreased apoptosis without significant effect on oxidative stress. CONCLUSION: The present study showed a putative therapeutic role of CeO2NPs in the treatment of 6-OHDA-induced Parkinsonian rats, and suggested their antioxidant and antiapoptotic effects as possible mechanisms for elevated striatal dopamine level and improved motor performance.

Behavioral and neuronal biochemical possible effects in experimental induced chronic mild stress in male albino rats under the effect of oral barley administration in comparison to venlafaxine.

Venlafaxine is an antidepressant of choice, whose effectiveness could be modified by a commonly used medicinal plant and nutrient. The current study had evaluated the barley extract (1 g/kg) when compared to or combined to venlafaxine (32 mg/kg) in a rat stress model. The present study was conducted on 40 male Wister albino rats; divided to five groups. Four groups were subjected to social chronic mild stress. Drugs or saline were orally daily administered one week before stress induction and extended up to ten weeks. Behavioral, brain biochemical tests and serum magnesium were assessed at the end. The study revealed significant change in the combined group on behavioral tests; forced swim test, elevated plus maze and saccharin preference test when compared to barley extract group. Furthermore, there was significant reduction in brain malondialdehyde level, no significant change in brain nitric oxide level, while significant increase in serum magnesium level was noticed. Whereas, the barley extract group recorded a lowest significant improvement in behavioral, brain and serum biochemical tests. It could be concluded that barley and venlafaxine together had muffled the oxidant stress and increased brain serotonin, serum magnesium level that might had a crucial role in experimental induced chronic mild stress in rats.