Key result
Rivaroxaban increases rat mitochondrial toxicity at lower doses but provides antioxidant protection at higher concentrations.
Why the study?
The effects of rivaroxaban on mitochondrial toxicity and oxidative stress in isolated kidney mitochondria were not well characterized.
Rivaroxaban demonstrates a concentration-dependent biphasic effect on isolated rat kidney mitochondria, inducing toxicity at lower concentrations and protection at higher concentrations.
May suggest rivaroxaban mitochondrial effects in rat kidney; leaves clinical relevance and human translation open.
Rivaroxaban as a small molecule is able to directly and reversibly inhibit the factor Xa. This study was designed to figure out the evaluation effect of rivaroxaban on mitochondria obtained from rat kidneys. We isolated mitochondria from rat kidneys using gradient centrifugation. Then, the toxicity parameters including succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) formation, mitochondrial swelling, mitochondrial membrane potential (MMP) collapse and cytochrome c release were measured in kidneys mitochondria following the exposure to rivaroxaban. The results showed that rivaroxaban (1.4 and 2.8 mM) raised the reactive oxygen species (ROS) generation, swelling in the mitochondria, collapse in the mitochondrial membrane potential (MMP) and cytochrome c release in the mitochondria isolated from kidneys. While, rivaroxaban at a higher concentration of 5.6 mM showed the opposite effect compared to other lower concentrations. The results indicate that rivaroxaban may have antioxidant effects at high concentrations. The results suggest that rivaroxaban (5.6 mM) has protective effects against oxidative stress and mitochondrial toxicity.
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Samiei et al. (2019) studied Mitochondrial toxicity and oxidative stress. Rivaroxaban was evaluated on Toxicity parameters including SDH activity, ROS formation, mitochondrial swelling, MMP collapse and cytochrome c release. Rivaroxaban at 1.4 and 2.8 mM increased ROS generation and mitochondrial toxicity in isolated rat kidney mitochondria, while a higher concentration of 5.6 mM showed protective antioxidant effects.
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