Hepatitis C virus infection is endemic in Egypt with the highest prevalence rate in the world. Without treatment, most acute infections lead to chronic, followed by cirrhosis and hepatocellular carcinoma. Sofosbuvir acts like a nucleos(t)ide analogue that specifically inhibits hepatitis C virus replication. Our study aimed to explore the molecular mechanisms and the possible side effects of the therapeutic dose of sofosbuvir on mitochondrial biogenesis and functions of liver, muscle and ovary tissues of young normal female rats and explore the possible prenatal effect of Sofosbuvir on the embryos of the exposed mother. The study was conducted on female albino rats 2 months old that was classified into 2 groups. Group I (Control group): 20 healthy female rats and Group II (exposed group): 20 female rats that was supplemented with 4 mg/kg of sofosbuvir drug for 3 months. At the end of the treatment period, 10 normal and 10 exposed female rats will be sacrificed and dissected out to obtain blood, ovary, liver and muscles. Pregnancy will be induced in 10 control females and 10 exposed females by mating with healthy male rats overnight. At gestational day 17 (GD 17) pregnant control females and pregnant exposed females will be sacrificed by cervical dislocation. The embryos with their membranes and placentas will be quickly dissected out of the uterine horns. Each embryo will be dissected to obtain the fetal liver, and muscles. The reported toxicity was mediated through suppression of Peroxisome proliferator-activated receptor gamma coactivator- 1alpha (PGC-1α), mitochondria transcription factor A that impair mitochondrial biogenesis that manifested a decline in mitochondrial DNA copy number. Also, sofosbuvir suppresses the expression of DNA polymerase γ and declines the mitochondrial NADH dehydrogenase subunit-5 content that impair the mitochondrial functions. According to our results, the ovarian tissue is the most affected organ followed by the liver and placenta while muscle tissue appears to resist sofosbuvir-induced mitochondrial toxicity. In conclusion, the effects of sofosbuvir on the ovarian mitochondrial biogenesis and functions was found to not just affect the exposed females but unfortunately may have long-lasting consequences by impairing the embryonic development and transfer these mitochondrial abnormalities to next generations.
Name: Rana Hassan Mahmoud Hassan Khafaga
Mobile: (+2011)41274363 – (+2010)24273634
E-mail: Ranahassanmahmoud@gmail.com, Ranahassanmahmoud@alexu.edu.eg
Nationality: Egyptian
Birth date: 4\11\1989
Marital State: Married
General Certificate of Secondary Education, Preparatory Education, Primary Education and Kinder garden: Sacred Heart School, Alexandria, Egypt, since 1995 to 2008
Graduate, Class of 2012, Alexandria University, Faculty of science, Biochemistry Department
Major: Biochemistry
Minor: Chemistry
Grade: Cumulative GPA: 3.86 out of 4, Percentage: 95.80% (first on biochemistry Department, and fifth on the whole university)
Current activity:
Professional category: Assistant lecturer at Biochemistry department at Medical Research Institute (MRI), Alexandria University, Egypt.
I am recently a student in Ph.D degree in MRI Alexandria University since February 2018
– Working on a Project accepted by STDF organization titled by: Short-term and long-term trans-generational side effects of Sofosbuvir: Experimental study on female rats, 2019.
Certificates, courses and conferences:
The Fourth international conference on new horizons in basic and applied sciences (ICNHBAS) 26 -29 july 2019, Hurghada, Egypt, oral speaker and best oral presentation.
The second international conference on biological, environmental sciences and applications, 25-28 July 2018, Hurghada, Egypt, oral speaker and best oral presentation.
The third international conference on new horizons in basic and applied sciences (ICNHBAS) August 2017, Hurghada, Egypt, oral speaker.
IELTS certificate with a score of 6.5 in 31st of December 2015.
Third workshop on molecular therapeutics and degenerative medicine from 7th to 9th of October 2015 at the faculty of pharmacy, Alexandria University.
Second workshop on molecular therapeutics and introduction to molecular biology techniques from 15th to 18th of December 2014 at the faculty of pharmacy, Alexandria University.
6th international conference and 18th annual conference (Multi-disciplinary approach in cancer management), from 23 – 26 September 2014.
Biological Fluids between Routine Laboratory, Investigations and New Modern Technology VI, 14 July 2012- 19 July 2012
First aid and injections, Aug 2011
One international publication in American journal of biomedical sciences accepted in 18/3/2020, entitled by: The Effect of Graviola Leaves Extract on the Progression of Pancreatic Cancer in Rats
Reading (Science books, Poetry, and Novels).
Adventures and traveling
Playing tennis and coach trainer in gym
Making new friendships and communicating with others of several cultures