Mechanistic approach for the toxic effects of perfluorooctanoic acid on isolated rat liver and brain mitochondria

Abstract

<jats:sec><jats:title>Background:</jats:title><jats:p> Perfluorooctanoic acid (PFOA) is one of the most widely used perfluoroalkanes as surfactants, lubricants and processing aids in the production of polymers, which has also been detected in the environment, wildlife and human body. Animal studies indicated that PFOA caused a wide array of toxic effects including liver and brain dysfunction, carcinogenicity and reproductive and developmental toxicity. Based on the established role of mitochondria-mediated pathways in the observed toxic effects of many drugs and chemicals, in this study, the potential toxic effects of PFOA on mitochondria isolated from rat liver and brain have been investigated. </jats:p></jats:sec><jats:sec><jats:title>Method:</jats:title><jats:p> Mitochondria were isolated by differential centrifugation method and incubated with different concentrations of PFOA (0.5–1.5 mM). The effects of PFOA were assessed on a series of mitochondrial parameters including reactive oxygen species (ROS) formation, activities of mitochondrial complexes I/II/III, reduced glutathione (GSH) content, adenosine triphosphate (ATP) level, membrane potential, lipid peroxidation (LPO), mitochondrial swelling and cytochrome c release. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> The data on liver mitochondria indicated that PFOA-induced ROS elevation in both mitochondrial complexes I and III, mitochondrial membrane potential collapse, swelling, cytochrome c release and decreased ATP level which induces apoptosis or necrosis. On brain mitochondria, PFOA showed fairly similar effects on the above-mentioned parameters. However, different results were obtained when the effect of PFOA was assessed on LPO and complex II activity. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> Due to the fact that PFOA had toxic effects on the mitochondria isolated, it could be suggested that mitochondrial toxicity could be a plausible mechanism for the toxic effects of this fluorochemical on liver and brain function. </jats:p></jats:sec>

Venlafaxine-Induced Cytotoxicity Towards Isolated Rat Hepatocytes Involves Oxidative Stress and Mitochondrial/Lysosomal Dysfunction

“…37 Various concentrations of VEN incubated with 100μL of mitochondrial suspensions equal to 500 μg protein/mL at 37 °C for 30 min pursued by the addition of MTT into the medium and on their incubation time for 30 min at 37°C. The absorbance of produced purple formazan was detected with an ELISA reader (Biotek, ELx800, USA).…”

Maternal exposure causes mitochondrial dysfunction in brain, liver, and heart of mouse fetus: An explanation for perfluorooctanoic acid induced abortion and developmental toxicity

“…While, Verma et al showed observed defects in ADHD strongly is associated with mitochondrial pathology . Also, another study has been reported mitochondrial toxicity could be a plausible mechanism for the toxic effects of PFOA on brain and liver function . PFOA has been reported to cause adenomas of pancreas, testes and liver of animals and delayed development of the mammary gland .…”

“…12 Also, another study has been reported mitochondrial toxicity could be a plausible mechanism for the toxic effects of PFOA on brain and liver function. 13 PFOA has been reported to cause adenomas of pancreas, testes and liver of animals and delayed development of the mammary gland. 14 Effects of PFOA on the liver can occur at lesser concentrations.…”

Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries

“…Animal studies have also shown that exposure to PFOA generates oxidative stress and apoptosis in vitro and in vivo: PFOA exposure significantly inhibited luteal function via oxidative stress and apoptosis in pregnant mice, induced oxidative stress in mouse epididymis and ROS elevation in isolated rat liver and brain mitochondria . The role of ROS within the female reproductive system is complex.…”