The Anti-fibrotic and Anti-inflammatory Potential of Bone Marrow-Derived Mesenchymal Stem Cells and Nintedanib in Bleomycin-Induced Lung Fibrosis in Rats.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive lung damage. Tyrosine kinase inhibitors are approved to treat people with IPF while bone marrow-derived mesenchymal stem cell therapy was previously suggested to inhibit pulmonary fibrosis through the alveolar epithelial cell repair. The present study aimed to evaluate the anti-inflammatory and anti-fibrotic effect of the bone marrow-derived mesenchymal stem cell (BM-MSC) therapy in comparison with nintedanib, a tyrosine kinase inhibitor, on improving survival in bleomycin-induced lung fibrosis in rats. Moreover, the combined therapy of BM-MSCs and nintedanib will be evaluated. In the present study, IPF was induced through intra-tracheal instillation of bleomycin (5 mg/kg) in rats then treatments were administered 14 days thereafter. Nintedanib (100 mg/kg, I.P.) was administered daily for 28 days, while BM-MSCs were injected once intravenously in tail vein in the dose 1 × 106 cells/ml/rat. In the present study, both treatment regimens effectively inhibited lung fibrosis through several pathways, suppressing tumor growth factor-ß (TGF-ß)/SMAD3 expression which is considered the master signaling pathway. Nintedanib and BLM-MSCs exerted their anti-inflammatory effect through minimizing the expression of TNF-α and IL-6. In addition, the histopathological examination of the lung tissue showed a significant decrease in the alveolar wall thickening, in the inflammatory infiltrate, and in the collagen fiber deposition in response to either nintedanib or BM-MSC and their combination. In conclusion, the therapeutic pulmonary anti-fibrotic activity of nintedanib or BM-MSC is mediated through their anti-inflammatory properties and inhibition of SMAD-3/TGF-ß expression.

Hesperidin attenuates benzo[alpha] pyrene-induced testicular toxicity in rats via regulation of oxidant/antioxidant balance.

Benzo[alpha]pyrene (BaP) is one of the polycyclic aromatic hydrocarbons, which has shown carcinogenic, teratogenic, and mutagenic potentials. The reproductive toxicity of BaP in male was not well investigated. Thereby, we have addressed in the current study the testicular toxicity of BaP and the postulate whether or not the citrus flavonoid, hesperidin (HDN), could ameliorate such toxicity in male Swiss albino rats. In this sense, animals were challenged with BaP (50 mg/kg/day, orally) for 10 consecutive days. HDN (200 mg/kg/day, orally) was administered ahead of BaP challenge for 10 consecutive days. BaP induced testicular toxicity that was well characterized histologically and biochemically. It decreased the relative testis weight and induced pyknosis and necrobiotic changes as well as chromatolysis in the nuclei of the spermatocytes in the seminiferous tubules. It also markedly deteriorated epididymal function as shown by decreased sperm count, motility, and daily sperm production. The polyaromatic hydrocarbon also reduced the testicular activities of lactate dehydrogenase (LDH-X), superoxide dismutase (SOD), and glutathione-S-transferase (GST). Besides, it decreased the testicular reduced glutathione (GSH) but increased malondialdehyde (MDA) contents. Prior administration of HDN ahead of BaP challenge ameliorated all the histological and biochemical alterations induced by BaP. It improved the epididymal function and mitigated the injurious effects of BaP on the seminiferous tubules. In conclusion, HDN has proven protective effects in BaP-induced testicular toxicity paradigm, and this protection resides, at least in part, on its antioxidant properties.