Cadmium-induced adrenal cortical autophagy in rats: possible modulation by sildenafil

Background: The link between autophagy, inflammatory bowel disease, ischaemic injury and cancer had been established. Reasonable evidence is available for cadmium to be related to certain cancers. Sildenafil had been investigated to modulate oxidative stress mechanisms. The aim of this study is to investigate cadmium-induced adrenal cortical autophagy and to declare possible modulation by sildenafil.Materials and methods: Twenty four Wistar rats weighing 150–200 g were randomly and equally assigned into: control group, sildenafil (20 mg/kg/day orally) exposed group, cadmium group (cadmium chloride 1 mg/kg/day SC), cadmium + sildenafil group (rats received cadmium concomitant with sildenafil). Euthanasia was done 4 weeks from the beginning of experiment; adrenal glands were subjected to biochemical, histological, ultrastructural and immunnohistochemical assessment.Results: Control and sildenafil exposed groups exhibited nearly similar results. Cadmium had produced adrenal cortical apoptosis and ultrastructural derangement of cell organelles. Cadmium-induced autophagy was detected by ultrastructural abundance of enlarged lysosomes and significant (p < 0.05) increase in the optical density of lysosomal associated membrane protein 2 immunoexpression. Sildenafil taken with cadmium had decreased adrenal cortical autophagy, significantly modulated the adrenal gland superoxide dismutase and malondialdehyde compared to cadmium group. Also, the optical density of nuclear factor kappa B (NF-kB) and caspase-3 immunoexpression was significantly decreased in cadmium + sildenafil compared to cadmium group.Conclusions: Cadmium might induce adrenal cortical autophagy in rats and sildenafil might show an ameliorating effect probably through enhancement of antioxidant defence mechanism and modulation of NF-kB

Febuxostat ameliorates methotrexate-induced lung damage

Background: The intention of the present study was to assess the structural affection of the lung following methotrexate (MTX) overdose. The proposed underlying mechanisms involved in lung affection were studied. The possible modulation role of febuxostat over such affection was studied. Materials and methods: Twenty-four rats were divided into three groups: control, MTX-treated, febuxostat-treated. The study was continued for 2 weeks. Lung was processed for histological and immunohistochemical (inducible nitric oxide synthase [iNOS] and cyclooxygenase [COX]-2) studies. Inflammatory markers (tumour necrosis factor alpha [TNF-a], interleukin 1 [IL-1]), Western blot evaluation of nuclear factor kappa B (NF-kB) and oxidative/antioxidative markers were done. Results: Methotrexate-treated group exhibited inflammatory cellular infiltrations, thickened interalveolar septa, dilated congested blood vessels, extravasated blood, and apoptosis. The collagen fibres content increased 3-fold. MTX induced lung affection through oxidative stress (increase MDA/decrease GSH, SOD) and apoptosis. It induced sterile inflammation through an increase of NF-kB (2-fold), IL-1 (3-fold) and TNF-a (3-fold), COX-2 cells (2.5-fold) and iNOS (6-fold). With the use of febuxostat, the normal lung architecture was observed with a bit thickened interalveolar septum and extravasated blood. The collagen fibres content was minimal. Decrement of oxidative stress and sterile inflammation (COX-2 cells and iNOS were comparable to the control group. NF-kB, IL-1 and TNF-a became higher by 34%, 64% and 100%). Conclusions: The overdose of MTX displays inflammatory lung affection with residual fibrosis. It induces lung affection through oxidative stress, apoptosis and sterile inflammation. With the use of febuxostat, the normal lung architecture was preserved with a little structural affection or fibrotic residue. Febuxostat exerts its lung protection through its anti-inflammatory and antioxidant features

Green tea extract modulates lithium-induced thyroid follicular cell damage in rats

Background: The aim of the current work was to clarify the modulation role of green tea extract (GTE) over structural and functional affection of the thyroid gland after long term use of lithium carbonate (LC). The suggested underlying mechanisms participating in thyroid affection were researched. Materials and methods: Twenty-four Sprague-Dawley adult albino rats were included in the work. They are divided into three groups (control, LC, and concomitant LC + GTE). The work was sustained for 8 weeks. Biochemical assays were achieved (thyroid hormone profile, IL-6). Histological, histochemical (PAS) and immunohistochemical (caspase-3, TNF-α, PCNA) evaluations were done. Oxidative/antioxidative markers (MDA / GSH, SOD) and western blot evaluation of the Bcl2 family were done. Results: LC induced hypothyroidism (decrease T3, T4/increase TSH). The follicles were distended, others were involuted. Some follicles were disorganized, others showed detached follicular cells. Apoptotic follicular cells were proved (Bax and caspase-3 increased, Bcl2 decreased, Bax/Bcl2 ratio increased). The collagen fibers' content and proinflammatory markers (TNF-α and IL-6) increased. The proliferative nuclear activity was supported by increase expression of PCNA. Oxidative stress was established (increase MDA/decrease GSH, SOD). With the use of GTE, the thyroid hormone levels increased, while the TSH level decreased. Apoptosis is improved as Bax decreased, Bcl2 increased, and Bax/Bcl2 ratio was normal. The collagen fibers' content and proinflammatory markers (TNF-α and IL-6) decreased. The expression of PCNA and caspase-3 were comparable to the control group. The oxidative markers were improved (decrease MDA/increase GSH, SOD). Conclusions: In conclusion, prolonged use of LC results in hypothyroidism, which is accompanied by structural thyroid damage. LC induced thyroid damage through oxidative stress that prompted sterile inflammation and apoptosis. With the use of GTE, the thyroid gland achieved its structure and function. The protecting role of GTE is through antioxidant, antifibrotic, anti-inflammatory, and antiproliferative effects