No abstract

CPF (chlorpyrifos) is an organophosphate pesticide used in agricultural and veterinary applications. Our experiment aimed to explore the effects of thymoquinone (TQ) and/or lycopene (LP) against CPF-induced neurotoxicity. Wistar rats were categorized into seven groups: first group served as a control (corn oil only); second group, TQ (10 mg/kg); third group, LP (10 mg/kg); fourth group, CPF (10 mg/kg) and deemed as CPF toxic control; fifth group, TQ + CPF; sixth group, (LP + CPF); and seventh group, (TQ + LP + CPF). CPF intoxication inhibited acetylcholinesterase (AchE), decreased glutathione (GSH) content, and increased levels of malondialdehyde (MDA), an oxidative stress biomarker. Furthermore, CPF impaired the activity of antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT) along with enhancement of the level of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β. CPF evoked apoptosis in brain tissue. TQ or LP treatment of CPF-intoxicated rats greatly improved AchE activity, oxidative state, inflammatory responses, and cell death. Co-administration of TQ and LP showed better restoration than their sole treatment. In conclusion, TQ or LP supplementation may alleviate CPF-induced neuronal injury, most likely due to TQ or LPs’ antioxidant, anti-inflammatory, and anti-apoptotic effects.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI), it is used in the treatment of depression; it has a toxic effect on the testis. Major depressive disorder is a pathological disorder associated with increased levels of the inflammatory cytokines tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), and IL-1 beta (IL-1β). Fluoxetine increase in malondialdehyde (MDA) and decrease in antioxidant enzyme activity SOD superoxide dismutase and catalase (SOD and CAT) and reduced glutathione (GSH). The study aimed to investigate whether vitamin D can reduce the oxidative damage caused by fluoxetine. Thirty -two adult male rats are divided into four groups and are included in the analysis. Animals in Group I (control group) were administered distilled water by gavage. Groups II: animals were given a dose of 10 mg/kg of fluoxetine (fluoxetine treated group) orally by gavage daily for 4 weeks. Group III (vitamin D group) animals received intramuscular VD (1,000 IU/kg; 3 days/week for 4 weeks. Group IV (fluoxetine+ vitamin D): drugs were given in the same previous doses for 4weeks. Blood samples were obtained 24 hours after the last dose of each drug. The biochemical results showed that fluoxetine significantly increased oxidative stress in testicular tissue and inflammatory markers in serum. The in-depth investigations supported that administering the fluoxetine combined with vitamin D reduced the testicular damage to a marked level and normalized all relevant markers. It was concluded that the oxidative stress induced by fluoxetine administration in rats could be reduced by vitamin D supplementation.

Although the classic form of asthma is characterized by chronic pneumonitis with eosinophil infiltration and steroid responsivity, asthma has multifactorial pathogenesis and various clinical phenotypes. Previous studies strongly suggested that chemical exposure could influence the severity and course of asthma and reduce its steroid responsiveness. Cypermethrin (CYP), a common pesticide used in agriculture, was investigated for the possible aggravation of the ovalbumin (OVA)-induced allergic pneumonitis and the possible induction of steroid resistance in rats. Additionally, it was investigated whether pirfenidone (PFD) could substitute dexamethasone, as an alternative treatment option, for the induced steroid resistance. Fifty-six male Wistar albino rats were randomly divided into seven groups: control, PFD alone, allergic pneumonitis, CYP alone, allergic pneumonitis/CYP-exposed, allergic pneumonitis/CYP/dexamethasone (Dex), and allergic pneumonitis/CYP/PFD-treated groups. Allergic pneumonitis was induced by three intraperitoneal OVA injections administered once a week, followed by an intranasal OVA instillation challenge. CYP (25 mg/kg/d), Dex (1 mg/kg/d), and PFD (100 mg/kg/d) were administered orally from day 15 to the end of the experiment. Bronchoalveolar lavage fluid (BALF) was analyzed for cytokine levels. Hematoxylin and eosin (H&E) and periodic acid Schiff (PAS)-stained lung sections were prepared. Immunohistochemical identification of p38 MAPK and lung macrophages was performed. The inflammatory/oxidative status of the lung and PCR-quantification of the STAT6, p38 MAPK, MUC5AC, and IL-13 genes were carried out. The allergic pneumonitis-only group showed eosinophil-mediated inflammation (p < 0.05). Further CYP exposure aggravated lung inflammation and showed steroid-resistant changes, p38 activation, neutrophil-mediated, M1 macrophage-related inflammation (p < 0.05). All changes were reversed (p < 0.05) by PFD, meanwhile not by dexamethasone treatment. Pirfenidone could replace dexamethasone treatment in the current rat model of CYP-induced severe steroid-resistant asthma via inhibiting the M1 macrophage differentiation through modulation of the STAT6/p38 MAPK pathway.

Background: bleomycin-induced lung toxicity and oxidative damage by decreasing the deactivating enzyme, genetic vulnerability, and released cytokines of inflammation. Melatonin has a free radical detoxifying effect, coenzyme Q10 has a strong antioxidant effect. Aim of the study: this study aimed to evaluate the possible protective role of melatonin and coenzyme Q10 in bleomycin-induced lung injury in Albino rats. Material and Methods: forty male Albino rats were categorized into five groups; group I (control group), group II (bleomycin group): rats were given a single dose of bleomycin intra-tracheal for inducing lung injury, group III (melatonin group): rats were given melatonin for three weeks after intratracheal installation of bleomycin, group IV (coenzymeQ10 group): rats were given coenzymeQ10 for three weeks after intratracheal installation of bleomycin and group V (combined melatonin and Co Q10 group): rats were given a combination of melatonin and coenzyme Q10for three weeks after induction of bleomycin lung toxicity. Lung tissues were prepared for biochemical, histological and immunohistochemical studies. Results: bleomycin produced a significant increase in the level of malondialdehyde and a significant reduction in glutathione peroxidase activity in lung tissues with loss of normal histological lung architecture, significant elevation in main area percent of collagen fibers deposition and caspase-3 immuno positive expression. In group III melatonin enhanced a significant improvement in the biochemical changes, moderate prevention of histopathological changes in lung tissue with a significant reduction in main area percent of collagen fibers deposition and caspase-3 immuno positive expression. While, in group IV co enzyme Q10 enhanced non significant improvement in the biochemical changes, mild prevention of histopathological changes and non-significant reduction in main area percent of collagen fibers deposition and caspase-3 immuno positive expression. Using a combination of both drugs in group V enhanced a significant improvement in the biochemical changes and almost preservation of normal histological architecture of the lung tissue. Conclusion: administration of both melatonin and coenzyme Q10 produced almost a complete recovery of bleomycin induced lung injury.