USA (Commonwealth Union)_ A first-of-its-kind study explains how a routinely used medicine to treat HIV and hepatitis promotes kidney disease and renal damage. The research is yet to be published in the journal Function. Drug toxicity, the detrimental effects of drugs on the body’s organs, is a major cause of kidney illness and is responsible for an estimated 25% cases of acute renal damage. Additionally, kidney toxicity is a common factor for the failure of novel medication development.
In case of drug toxicity, the mitochondrial function, which is the energy center of the cell, gets frequently impaired, although it is unclear how or why this occurs. Tenofovir disoproxil fumarate is the primary and standard therapy for HIV and hepatitis B across the world. Tenofovir, which is the active component in the drug, is a nephrotoxic, and it is the drug that harms the kidneys. To investigate the processes underlying this nephrotoxicity, researchers utilized a human-derived cell line that had many of the similar properties as proximal tubule cells of the kidneys.
The study exposed the cells to the medication for 24 hours and employed cutting-edge imaging tools and complete metabolic screening to assess in detail how the cells responded to the tenofovir. The researchers stated that they used higher than the normal doses of drug. According to them, [tenofovir disoproxil fumarate] toxicity in humans is a cumulative phenomena, which is likely explained by the buildup of hazardous compounds inside [proximal tubule] cells over time.
The study team discovered that a metabolite, which is a byproduct of the drug’s breakdown, of tenofovir decreased complex V activity and expression in treated cells. Complex V is a protein complex in mitochondria that turns food-derived energy into a form that cells can utilize. In the biopsy samples of people with tenofovir-induced kidney illness, a drop in complex V levels was also detected. The decrease in complex V activity indicates why drug-induced mitochondrial dysfunction develops.
According to the researchers, “By combining high-throughput imaging with detailed metabolic profiling, we were able to identify for the first time the mitochondrial phenotype of [tenofovir disoproxil fumarate] toxicity in renal epithelial cells. We envisage that this approach could be harnessed not only to investigate other drugs and toxins, but also for further purposes, such as uncovering novel genetic regulators of transport and metabolism in epithelia”.
