Study: Cellular Detoxification of Antiretroviral Drugs

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A breakthrough study by a young UKZN PhD student has the potential to bring down the toxic side-effects of antiretroviral therapy in patients with HIV and AIDS.

Ms Savania Nagiah, a Medical Biochemistry PhD student at UKZN’s School of Laboratory Medicine and Medical Sciences (LMMS), identified a specific epigenetic mechanism (microRNA 124a) as a regulator of a protein that facilitates cellular detoxification of antiretroviral drugs.

Nagiah presented her study titled, “Differential Regulation of ABCC4 by microRNA-124a in HepG2 cells exposed to antiretroviral drugs” at the 2015 College of Heath Sciences Research Symposium held recently at UKZN’s Medical School.

According to Nagiah there are many adverse side effects associated with the long-term use of antiretroviral therapy.

‘Many of the side effects relate to altered metabolism.  The liver is central to metabolic processes,’ she said.  ‘The liver is also the site of metabolism for drugs. The detoxification of these drugs at the cellular level in the liver may play a role in determining toxic outcomes.’

Nagiah’s PhD focused on molecular mechanisms of liver toxicity induced by antiretroviral drugs. She looked at a specific cellular protein (ABCC4) that exports metabolised drugs from the cell.

She studied how different antiretroviral drugs induce different activity of the ABCC4. She then investigated how changes in the activity of ABCC4 may be regulated. She identified microRNA-124a as a negative regulator of ABCC4.

‘Manipulation of microRNA-124a may be a form of therapeutic intervention in antiretroviral-associated liver toxicity,’ she added.  ‘Antiretroviral therapy is a lifelong treatment and the long-term side effects cannot be ignored. By identifying the cause of toxicity at a molecular level, targeted therapies can be developed to address the adverse health outcomes observed like lipodystrophy, metabolic syndrome and type 2 diabetes.’

Nagiah’s in vitro study experiments were conducted at the Medical Biochemistry lab which is headed by Professor Anil Chuturgoon.

She said her work has not yet reached the patient level, but it does have implications for long term therapy development since it has relevance for people experiencing the side effects of long-term antiretroviral therapy.

‘If therapeutic interventions are developed from the findings of my work it will improve the quality of life of these patients and improve adherence,’ she said.

Nagiah is passionate about research and would like to continue with scientific research.

‘I am based at the Department of Medical Biochemistry, which has a predominantly female postgraduate class,’ continued Nagiah. ‘This awesome department is headed by Professor Anil Chuturgoon whose guidance and support has been the driving force behind this ambitious group of young scientists in which I feel privileged to include myself. Dr Alisa Phulukdaree, who was based at UKZN up until last year, is my mentor.  She pushed me to pursue my masters and PhD. I owe any success I have to these two individuals.’

Nagiah is the eldest of three children.  Her 17-year-old sister is in matric and her 24-year-old brother works in the motor industry with their father.  Nagiah’s mother is a teacher.

‘I’m the only person in my family who has taken an interest in science,’ she said.

Nombuso Dlamini