Saffron extract attenuates Sofosbuvir-induced retinal neurodegeneration in albino rat.

Sofosbuvir is a novel drug candidate for the treatment of hepatitis C viral infection; however, vision loss is one of its growing adverse effects. Saffron is a natural biomolecule with a high antioxidant potential that has been efficiently used in some diseases caused by oxidative stress. This study evaluated Sofosbuvir's neurodegenerative effect on the retina of albino rat and examined the potential protective role of saffron aqueous extract. Twenty-one adult male albino rats were randomly divided into three groups: Control, Sofosbuvir-treated (41.1 mg/kg /day for 6 weeks), and Sofosbuvir + Saffron co-treated groups. Retinal specimens were biochemically analyzed for malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. In addition, light and transmission electron microscopic examination, as well as immunohistochemical staining for Caspase-3, COX-2, and GFAP were performed. Sofosbuvir treatment caused a significant increase in retinal MDA, IL-6, and TNF-α levels coupling with a significant decrease in retinal total antioxidant capacity level. Histopathological findings revealed disturbed retinal architecture, detached pigment epithelium, vacuolated photoreceptors, in addition to a significant decrease in the thicknesses of both outer and inner nuclear layers, and the number of ganglionic cells. Ultrastructural examination revealed extensive degenerative changes in all retinal layers. Caspase-3, COX-2, and GFAP immunohistochemical expressions were significantly increased. Meanwhile, concomitant treatment with Saffron significantly improved retinal redox status, inflammation, histological, and ultrastructural parameters. Saffron may protect the retina from the hazardous effects of Sofosbuvir. Saffron could be used as an adjuvant therapy to protect patients receiving Sofosbuvir from retinal damage.

Redox status, inflammation, necroptosis and inflammasome as indispensable contributors to high fat diet (HFD)-induced neurodegeneration; Effect of N-acetylcysteine (NAC).

Adequate dietary intake has a crucial effect on brain health. High fat diet (HFD) rich in saturated fatty acids is linked to obesity and its complications as neurodegeneration via inducing oxidative stress and inflammation. The present study aimed to evaluate the effect of HFD on cerebral cortex in addition to shedding the light on the modulatory role of N-acetylcytsteine (NAC) and its possible underlying biochemical and molecular mechanisms. Twenty eight male Wistar rats were equally and randomly divided into four groups. Group III, and group IV were fed on HFD (45% kcal from fat) for 10 weeks. Group II and group IV were treated with NAC in a dose of 150 mg/kg body weight via intraperitoneal route. Body weight, blood glucose, serum insulin, insulin resistance index, cerebral cortex redox and inflammatory status were evaluated. Cerebral cortex receptor-interacting serine/threonine-protein kinase3 (RIPK3), mixed-lineage kinase domain-like protein (MLKL), nod like receptor protein 3 (NLRP3), interleukin (IL)-18 levels were determined by immunoassay. In addition, apoptosis-associated speck-like proteins (ASC) expression by real-time PCR; inducible nitric oxide synthase (iNOS), glial fibrillary activating protein (GFAP) and matrix metalloproteinase-9 (MMP-9) expression by immunohistochemistry were evaluated. NAC supplementation protected against HFD-induced gain of weights, hyperglycemia, and insulin resistance. Furthermore, NAC improved redox and inflammatory status; decreased levels of RIPK3, MLKL, NLRP3, IL-18; down-regulated ASC, iNOS, GFAP and MMP-9 expression; and decreased myeloperoxidase activity in cerebral cortex. NAC could protect against HFD-induced neurodegeneration via improving glycemic status and peripheral insulin resistance, disrupting oxidative stress/neuroinflammation/necroptosis/inflammasome activation axis in cerebral cortex. NAC may represent a promising strategy for conserving brain health against metabolic diseases-induced neurodegeneration.

Mechanistic evaluation of AMPK/SIRT1/FXR signaling axis, inflammation, and redox status in thioacetamide-induced liver cirrhosis: The role of Cichorium intybus linn (chicory)-supplemented diet.

Liver cirrhosis is a scene profitable to the advance of hepatocellular carcinoma (HCC). The current work was engrossed to weigh the potential role of Cichorium intybus linn against thioacetamide (TAA)-induced liver cirrhosis and their probable underlying biochemical and molecular mechanisms. farnesoid-X-receptor (FXR) expression, proliferating cell nuclear antigen (PCNA) immunoreactivity, and activated AMP protein kinase (pAMPK), sirtuin-1 (SIRT1), and interleukin-6 (IL6) levels were estimated in hepatic tissue by real-time PCR, immunohistochemistry, and immunoassay, respectively. C. intybus linn supplementation caused a significant improvement in serum liver enzymes, albumin, bilirubin levels, tissues redox status and hepatic histological features in addition to decreased IL6 level, hydroxylproline content, and PCNA immunoreactivity. On contrary, increased pAMPK/SIRT1 levels and upregulated FXR gene expression were observed. C. intybus linn could feasibly protect against TAA-induced hepatic damage, fibrosis, and cirrhosis by relieving oxidative stress and by interruption of the inflammatory pathway via AMPK/SIRT1/FXR signaling. PRACTICAL APPLICATIONS: No specific therapies are available until now to target the underlying mechanisms for protection against liver diseases. Herbal protection is widely available and cheap with no side effect. Cichorium intybus linn, a natural supplement, is proved in this current work to have the potential of being hepatoprotectant, antioxidant, and anti-inflammatory agents, thus reducing the risk of hepatic cirrhosis.