Ameliorative effects of sildenafil against carbon tetrachloride induced hepatic fibrosis in rat model through downregulation of osteopontin gene expression.

The liver carries out many essential tasks, such as synthesising cholesterol, controlling the body's storage of glycogen, and detoxifying metabolites, in addition to performing, and regulating homeostasis. Hepatic fibrosis is a pathological state characterized by over accumulation of extracellular matrix (ECM) including collagen fibers. Sildenafil (a selective inhibitor of type 5 phosphodiesterase) has anti-inflammatory, antioxidant and anti-apoptotic properties. It is commonly used to treat erectile dysfunction in male. The purpose of the current investigation was to evaluate sildenafil's hepatoprotective potential against liver fibrosis in rats that was caused by carbon tetrachloride (CCl4). Liver enzymes and oxidative markers as well as profibrotic genes were determined. The findings showed that sildenafil alleviates the hepatic dysfunctions caused by CCl4 by restoring normal levels of ALT, AST, and GGT as well as by restoring the antioxidant status demonstrated by increased glutathione (GSH), and catalase. In addition, a significantly down-regulated the mRNA expressions of profibrotic genes [collagen-1α, IL-1ß, osteopontin (OPN), and transforming growth factor-ß (TGF-ß)]. Additionally, sildenafil lessens the periportal fibrosis between hepatic lobules, congestion and dilatation in the central vein, and the inflammatory cell infiltrations. As a result, it is hypothesized that sildenafil may be helpful in the management of hepatotoxicity brought on by CCl4 through suppressing OPN.

Protective effect of quercetin on pulmonary dysfunction in streptozotocin-induced diabetic rats via inhibition of NLRP3 signaling pathway.

Diabetes mellitus (DM) is a dysmetabolic disease characterized by chronic hyperglycemia. In the developed countries, DM is the commonest life style disease that affects both old and young age. Nod-like receptor protein-3 (NLRP3)-mediated pyroptosis may in fact aid in the development of diabetic complications. Quercetin is a natural flavonoid, can be present in natural foods and plants. Many studies have reported the antioxidant role of quercetin on different tissues, but its effects on NLRP3-mediated pyroptosis in diabetic lung are unclear. The current study aimed to assess quercetin's protective effects on lung function, oxidative stress, and NLRP3-mediated pyroptosis in Wister rats exposed to streptozotocin (STZ)-induced DM. Forty male Wister rats were randomly allocated into four equal groups. The groups of rats were as follows: group 1 (G1) was kept under normal control conditions; G2 was injected I/P quercetin at a dose of 30 mg/kg b.wt., daily for 30 days; G3 and G4 were injected with a single dose of streptozotocin (STZ) 50 mg/kg b.wt. I/P to induce DM. After 72-h post diabetes induction, the rats of G4 were treated with quercetin as a manner in the second group. The results showed that quercetin ameliorates the pulmonary dysfunctions caused by DM through restoring the levels of glucose, insulin, and arterial blood gases, as well as the oxidative markers. Also, NLRP3-pyroptosis-mediated IL1ß was inhibited. Quercetin also reduces the effect of DM on the lung by decreasing the pathological changes in the lung. In conclusion, NLRP3 inflammasome-induced pyroptosis may aggravate lung injury in diabetic rats. Quercetin has the potential to ameliorate diabetes induced pulmonary dysfunction by targeting NLRP3.