This study aimed to explore the potential protective effect of α-lipoic acid on busulfan-induced pulmonary fibrosis in rats.Main methods: Eighteen adult male rats were divided into 3 groups; control, busulfan, and busulfan plus α-lipoic acid groups. Lung index ratio, serum level of proinflammatory cytokine were assessed. The activities of antioxidant enzymes and lipid peroxidation products were estimated in the lung tissues in addition to the histopathological analyses. The deposition of the collagen in the lung tissues was evaluated by Sirius red staining. The expressions of α-smooth muscle actin (α-SMA), TNF-α, and Caspase 3 were determined immunohistochemically.The pulmonary expression of COX-2 and NOX-4 mRNA was assessed using qRT-PCR. Key findings: Administration of ALA significantly protect the lung against BUS-induced pulmonary fibrosis, besides the upregulation of antioxidants, and downregulation of pro-inflammatory cytokines. Also, it reduced collagen deposition that associated with a decreased expression of α-SMA, TNF-α, and Caspase 3 in the lung tissues.Moreover, ALA significantly upregulated the expression of COX-2 concomitant with the downregulation of elevated NOX-4. Significance: ALA attenuates the lung cytotoxicity of busulfan through its anti-inflammatory, anti-apoptotic, and antifibrotic effects that may be mediated by upregulation of COX-2 and downregulation of NOX-4.

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Non-alcoholic steatohepatitis (NASH) is a worldwide health problem. Alternate-day fasting (ADF), although thought to be aggressive, has proven safety and efficacy. We aimed to evaluate the effect of short-term ADF against already established high-fat-fructose (HFF)-induced NASH, independent of the amount of calorie intake, and to study the effect of ADF on lipogenesis, apoptosis, and hepatic inflammation. Male Sprague Dawley rats were divided into two groups: (1) negative control and (2) NASH group fed on HFF for 9 weeks, and then randomized into two subgroups of either HFF alone or with ADF protocol for 3 weeks. The ADF could improve HFF-related elevation in serum lactate dehydrogenase and could decrease the mRNA expression of lipogenesis genes; acetyl CoA carboxylase, peroxisome proliferator-activated receptor γ, and peroxisome proliferator-activated receptor α; apoptotic genes caspase-3, p53, and inflammatory cyclo-oxygenase 2; and immunohistochemical staining for their proteins in liver with upregulation of LC3 and downregulation of P62 immunoexpression. Moreover, ADF ameliorated HFF-induced steatosis, inflammation, ballooning, and fibrosis through hematoxylin and eosin, Oil Red O, and Sirius Red staining, confirmed by morphometric analysis, without significant weight loss. Significant correlation of morphometric parameters with levels of gene expression was found. These findings suggest ADF to be a safe effective therapeutic agent in the management of NASH

Obesity causes renal changes (ORC), characterized by defective renal autophagy, lipogenesis, enhanced macrophage infiltration and apoptosis. We hypothesize that Dasatinib, a tyrosine kinase inhibitor, may ameliorate changes associated with obesity. We the mice with either Obesogenic diet (OD) or a standard basal diet. After 12 weeks, the mice received either vehicle or Dasatinib 4 mg/kg/d for an additional four weeks. We examined serum creatinine, urea, lipid profile and renal cortical mRNA expression for lipogenesis marker SREBP1, inflammatory macrophage marker iNOS and fibrosis markers; TGFβ and PDGFA genes; immunohistochemical (IHC) staining for CD68; inflammatory macrophage marker and ASMA; fibrosis marker, LC3 and SQSTM1/P62; autophagy markers and western blotting (WB) for caspase-3; and, as an apoptosis marker, LC3II/I and SQSTM1/P62 in addition to staining for H&E, PAS, Sirius red and histopathological scoring. Dasatinib attenuated renal cortical mRNA expression for SREBP1, iNOS, PDGFA and TGFβ and IHC staining for CD68, ASMA and SQSTM1/P62 and WB for caspase-3 and SQSTM1/P62, while elevating LC3 expression. Moreover, Dasatinib ameliorated ORC; glomerulosclerosis, glomerular expansion, tubular dilatation, vacuolation and casts; inflammatory cellular infiltration; and fibrosis. Dasatinib is a promising therapy for ORC by correcting autophagy impairment, attenuating lipogenesis, apoptosis and macrophage infiltration by inducing antifibrotic activity.