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.

Pancreatic tumor is a lethal malignancy resistant to conventional current protocols for management including surgical intervention, chemotherapy, and radiation which possesses adverse effects. The present study was designed to evaluate the effects of an extract from Annona Muricata, known as Graviola. Graviola leaves extract (GLE) contain bioactive compound "annonaceous acetogenins" known for anticancer activity on cancer cell lines. This study aimed to explore the molecular mechanisms involved in the progression of pancreatic cancer PC including: redox status, oxidative stress, gene and microRNA expression, and the protective and therapeutic effect of GLE against PC. The study was divided into two phases of male Sprague Dawley rats; to study the protective effect of GLE in one using DMBA for (PC) induction, and GLE effect as adjuvant therapy, blood and pancreatic tissue samples were obtained for assessment of different parameters. These parameters indicated impaired liver and kidney functions in the positive control group (Group II) compared to control (Group I) and co-treated groups (Group III), while in phase II no changes were found, except in treated groups. Also lipid peroxidation, antioxidant capacity, levels of inflammatory cytokines, and expression of NF-κB, COX-2, VEGF-A, iNOS, TNF-α and miRNA levels (miRNA 21, 34a, and 200b) showed aberrant expression in positive control group compared to other groups in both phases. Our findings suggest that microRNAs imbalance in miRNA-21, miRNA-34a and miRNA-200b could be exploited as novel biomarkers for diagnostic and prognostic assessments of PC and as targets for therapy. Collectively, GLE showed significant cytotoxic activity against pancreatic carcinogenesis through multiple pathways motensive nonpregnant women; thereby, exposing them to cardiovascular risks in the near future.

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.