Background: Hepatitis C virus (HCV) infection is a global public health problem and Egypt has the highest HCV prevalence worldwide. Hence, global efforts target to eliminate HCV by 2030. Sofosbuvir is a nucleotide analogue inhibitor of HCV polymerase essential for viral replication. Animal studies prove that Sofosbuvir metabolites cross the placenta and are excreted in the milk of nursing animals. We aimed to investigate the possible effects of preconception maternal exposure to Sofosbuvir on mitochondrial biogenesis in prenatal fetal liver, skeletal muscle, and placental tissues. Methods: The study was conducted on 20 female albino rats divided into a control group receiving a placebo and an exposed group receiving 4 mg/kg orally/day for 3 months of Sofosbuvir. At the end of the treatment period, pregnancy was induced in both groups by mating with healthy male rats overnight. At gestational day 17, all pregnant female rats were sacrificed. Each fetus was dissected to obtain the fetal liver, skeletal muscle, and placental tissues. Results: The results of our study indicated that the exposure of young female rats to Sofosbuvir affects pregnancy outcomes. Fetal liver and muscle showed lower mitochondrial DNA-copy number (mtDNA-CN) by about 24% and 29% respectively, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and its downstream targets; nuclear respiratory factor-1 and mitochondrial transcription factor A. While the placental tissues showed different patterns, particularly elevated in mtDNA-CN by about 43%. Conclusions: The study provides preliminary evidence of the detrimental effects of Sofosbuvir on the pregnancy outcomes of the exposed females and may impair the placental and fetal organs’ development. These effects may be mediated through modulating mitochondrial homeostasis and functions.

Introduction: Epilepsy is a common neurological disorder; seizures and hyperexcitability are its defining features in the central nervous system (CNS). The condition known as status epilepticus (SE) can be fatal, as it involves seizures occurring. Epilepsy is typically treated with antiepileptic drugs (AEDs) like carbamazepine (CBZ). The present study aimed to establish a rat model of SE-like disease using the LiCl-pilocarpine and then utilize these rat models to evaluate the therapeutic potential of AST and/or CBZ in a solution form or loaded on NLCs via intranasal administration. Additionally, to investigate the potential molecular targets of AST and AST + CBZ-nanoformulations.Methods: After the treatment was completed, the rats underwent behavioral tests, including the rotarod and Morris Water Maze (MWM). They are then sacrificed and their brains were dissected to obtain the cerebral cortex and hippocampus for the assessment of neurotransmitters such as gamma-aminobutyric acid (GABA), serotonin, and dopamine; gene expression of GABA type A (GABAA) receptors subunits and gephyrin; indicators of inflammation like nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and High-Mobility Group Box 1 (HMGB1); antioxidant markers, including nuclear factor transcription factor E2-related factor 2 (Nrf2) and hem oxygenase-1 (HO-1).Results: The rats treated with the combination of AST and CBZ in nano-formulations seeing the best results.Discussion: Astaxanthin (AST) may reduce epilepsy-induced oxidative stress and neuronal cell death in the brain. Nano lipid carriers (NLCs) serve as better drug delivery carriers for lipophilic drugs such as CBZ and AST. AST exhibited potential anti-epileptic effects on its own, particularly as NLC-nanoformulations and when combined with conventional AEDs (CBZ).

Osteoporosis is the most common metabolic bone disorder affecting up to 40% of postmenopausal women, characterized by a reduction in bone mass leading to bone fragility and fractures. Herbal medication has been and remains commonly used instead of chemical drugs because of its minor side effects. Lepidium sativum L. (LS) or “hab arachad”, is a native shrub, which is well known as a good alternative medication for fracture healing. The aim of this study is to evaluate the effect LS extract loaded chitosan nanoparticles on gene expression of miR-142-3p and miR-23a in experimental rat model of osteoporosis. The osteoporosis was induced in rats by subcutaneous injection with methylprednisolone (3.5 mg/kg b.wt / day) for 4 weeks. Then osteoporotic rats were orally treated with 400 mg/kg b.wt /day LS extract, chitosan nanoparticles (CN) and 400 mg/kg b.wt /day LS extract loaded on chitosan nanoparticles for 12 weeks. Our results showed that treatment with LS, CN and LS loaded on CN ameliorated the biochemical bone indices with variable degrees, with a net results of enhanced serum calcium and phosphorus. Treated rats showed a significant decrease in the expression of miR-23a and a significant increase in the expression of miR-142-3p which emphasized the improvement of osteoporosis. The effect of treatment with LS and LS loaded on CN was confirmed by histopathological observations. All of these effects together with the safety and no adverse effects of LS and LS loaded on CN make it a promising therapeutic agent for management of Osteoporosis.

(1) Background: Hepatitis C virus (HCV) infection is endemic in Egypt, with the highest prevalence rate worldwide. Sofosbuvir (SOF) is a nucleos(t)ide analog that specifically inhibits HCV replication. This study aimed to explore the possible effects of the therapeutic dose of SOF on the mitochondrial biogenesis and functions of the liver, muscle, and ovarian tissues of young normal female rats. (2) Methods: This study was conducted on 20 female Wistar rats, classified into two groups, the control group and the exposed group; the latter was orally supplemented with 4 mg/kg/day of SOF for 3 months. (3) Results: The exposure to SOF impairs mitochondrial biogenesis via mitochondrial DNA copy number decline and suppressed mitochondrial biogenesis-regulated parameters at mRNA and protein levels. Also, SOF suppresses the DNA polymerase γ (POLG) expression, citrate synthase activity, and mitochondrial NADH dehydrogenase subunit-5 (ND5) content, which impairs mitochondrial functions. SOF increased lipid peroxidation and oxidative DNA damage markers and decreased tissue expression of nuclear factor erythroid 2-related factor 2 (Nfe2l2). (4) Conclusions: The present findings demonstrate the adverse effects of SOF on mitochondrial biogenesis and function in different tissues of young female rats, which mostly appeared in ovarian tissues.

Sofosbuvir (SOF), a nucleos(t)ide polymerase inhibitor, has been used during the past decade for mass treatment of viral hepatitis C in endemic countries like Egypt, increasing the exposure of women at childbearing age to SOF. This study investigated the long-lasting consequences of the pre-conceptional exposure of young female rats to SOF on the ovarian tissues of F1 offspring and explored the possible molecular mechanisms of these intergenerational effects at various levels. The study was conducted on young female rats that were divided into control group and SOF-exposed group at a dose of 4 mg/kg/day for three months. After that, pregnancy was induced in both groups by mating with healthy male rats. After delivery, the female neonates were followed for 4 months, and the ovarian tissues were collected to assess the studied parameters. Pre-conceptional exposure to SOF affected the ovarian functions of F1 offspring through modulation of estrogen receptors, ovarian Kiss1 and its receptor, increased lipid peroxidation marker, DNA oxidation marker, and redox-sensitive nuclear factor kappa B, and decreased nuclear erythroid-2-related factor 2, mitochondrial function, and biogenesis. SOF affected the ovarian function of the F1 offspring by inducing oxidative stress and inflammation, leading to the modulation of mitochondrial functions and biogenesis.

Hepatitis C virus (HCV) infection is a global public health problem and Egypt has the highest HCV prevalence worldwide. Hence, global efforts target to eliminate HCV by 2030. Sofosbuvir is a nucleotide analogue inhibitor of HCV polymerase essential for viral replication. Animal studies prove that Sofosbuvir metabolites cross the placenta and are excreted in the milk of nursing animals. We aimed to investigate the possible effects of preconception maternal exposure to Sofosbuvir on the mitochondrial biogenesis in prenatal fetal liver, skeletal muscle and placental tissues using female rats. The study was conducted on 20 female albino rats classified into 2 groups, control group including 10 healthy rats receiving placebo, and exposed group including 10 rats receiving 4 mg/kg of Sofosbuvir. At the end of the 3-month treatment period, pregnancy was induced in both groups by mating with healthy male rats overnight. At gestational day 17, all pregnant female rats were sacrificed. Each fetus was dissected to obtain the fetal liver, skeletal muscle and placental tissues. The results of our study indicated that the preconception exposure of young female rats to Sofosbuvir affects pregnancy outcomes, decreases fertility, and impacts mitochondrial biogenesis and functions in prenatal fetal liver, skeletal muscle and placental.