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Cyclophosphamide (CP)-induced lung toxicity is a remaining obstacle against the beneficial use of this chemotherapeutic agent. More considerations were given to the role of Alogliptin (ALO) in ameliorating CP-induced toxicities in many tissues. We designed this study to clarify the protective potential of ALO against CP-induced lung toxicity in rats. ALO was administered for 7 days. Single-dose CP was injected on the 2nd day (200 mg/kg: i.p.) to induce lung toxicity. Rats were divided into four groups: control, ALO-treated, CP-treated and ALO + CP-treated group. Leucocytic count, total proteins, LDH activity, TNF-α, and IL-6 were estimated in the bronchoalveolar lavage fluid (BALF). The oxidative/antioxidants (MDA, Nrf2, TAO and GSH), inflammatory (NFκB), fibrotic (TGF-β1) and apoptotic (PI3K/Akt/FoxO1) markers in pulmonary homogenates were biochemically evaluated. Rat lung sections were examined histologically (light and electron microscopic examination) and immunohistochemically (for iNOS and CD68 positive alveolar macrophages). CP significantly increased oxidative stress, inflammation, fibrosis, and apoptosis markers as well as deteriorated the histopathological pulmonary architecture. These hazardous effects were significantly ameliorated by ALO treatment. ALO protected against CP-induced lung toxicity by mitigating the oxidative, inflammatory and fibrotic impacts making it a promising pharmacological therapy for mitigating CP-induced lung toxicity. Graphical abstract

The effect of vitamin D on cardiac dysfunction after menopause is still under investigation. Therefore, we investigated the effect of vitamin D3 on cardiac apoptotic and structural changes in ovariectomized rats. Forty adult female albino rats were divided into 4 equal groups: sham rats, sham rats treated with vitamin D3, ovariectomized rats, and ovariectomized rats treated with vitamin D3 (500 IU/kg per day for 6 weeks, orally). Body mass, blood pressure, heart rate, and whole heart mass (WHM) were measured. Serum soluble receptors of advanced glycation end products (sRAGE), C-reactive protein, malondialdehyde, and total antioxidant capacity were estimated. Cardiac sections were stained with haematoxylin–eosin and Masson’s trichrome stain. Fas and FasL apoptosis-related proteins were detected by immunohistochemistry. Vitamin D3 treatment significantly decreased ovariectomy-induced cardiac Fas and FasL apoptosis-related proteins, whole heart mass, body mass, C-reactive protein, and malondialdehyde accompanied by decreased inflammation and reduced collagen deposition between cardiac muscle fibres. However, vitamin D3 significantly increased total antioxidant capacity and sRAGE in ovariectomized and sham treated groups. Our findings suggest that vitamin D3 treatment can prevent ovariectomy-induced cardiac structural and apoptotic changes in rats via increasing sRAGE and antioxidant activity. Our results suggest that vitamin D3 has therapeutic effect against postmenopausal cardiovascular disease.

Hyperthyroidism is associated with cardiac hypertrophy, fibrosis, and increased risk of cardiovascular mortality. Sacubitril/valsartan (LCZ696) is a new combined drug that has shown promise for the treatment of hyperthyroidism-associated heart failure; however, the underlying molecular mechanisms, including the contributions of epigenetic regulation, remain unclear. The present study was designed to investigate the therapeutic efficacy of LCZ696 and the potential contributions of microRNA regulation in a rat model of hyperthyroidism-induced cardiac hypertrophy. Cardiac hypertrophy was induced by intraperitoneal administration of levothyroxine. Sixty adult male Wistar rats were randomly allocated to four equal groups (15 rats each): control, cardiac hypertrophy (CH), CH + valsartan, and CH + LCZ696. Treatment with LCZ696 or valsartan significantly improved hemodynamic abnormalities, normalized serum concentrations of natriuretic peptide, fibroblast growth factor-23, and cardiac inflammatory markers compared to CH group rats. Treatment with LCZ696 or valsartan also normalized myocardial expression levels of autophagy markers, fibrotic markers, PPAR-ϒ, mir-377, and let-7b. In addition, both valsartan and LCZ696 ameliorated collagen deposition, ventricular degeneration, and various ultrastructural abnormalities induced by levothyroxine. The beneficial effects of LCZ696 were superior to those of valsartan alone. The superior efficacy of LCZ696 may be explained by the stronger modulation of miR-377 and let-7b.

Background: Gout is a metabolic disease strictly related to hyperuricemia. The associated intense inflammation and pain are triggered by the deposited monosodium urate crystals (MSU) in joints. The principal therapeutic strategies of gout involve the control of hyperuricemia and anti-inflammatory medications. Objectives: This study aimed to investigate the possible beneficial effects of ozone therapy, a well-known antioxidant, and an immunomodulation, on gouty arthritis and the underlying mechanisms. Methods : Acute gouty arthritis was induced in male albino rats via MSU crystals intra-articular injection in the ankle joint. The gouty arthritic rats received pre-treatment with ozone, colchicine (as a reference drug), or combination. Results : The obtained results of ozone therapy showed obvious reduction in the degree of ankle edematous swelling, pro-inflammatory cytokines, lipid peroxidation, the nucleotide binding oligomerization domain like receptor containing pyrin domain 3 (NLRP3), procaspase-1, caspase-1, interleukin-1β synovial tissue levels with enhancement of antioxidant defense system. Additionally, ozone therapy significantly attenuated the histological derangements in gouty arthritic rats. Conclusion : This study suggests that ozone is able to treat gouty arthritis and reducing synovial injury through an anti-inflammatory effect as well as antioxidant activity.