Mitochondrial Dysfunctions May Be One of the Major Causative Factors Underlying Detrimental Effects of Benzalkonium Chloride

Abstract

Benzalkonium chloride (BAC) is currently the most commonly used antimicrobial preservative in ophthalmic solutions, nasal sprays, and cosmetics. However, a large number of clinical and experimental investigations showed that the topical administration of BAC-containing eye drops could cause a variety of ocular surface changes, from ocular discomfort to potential risk for future glaucoma surgery. BAC-containing albuterol may increase the risk of albuterol-related systemic adverse effects. BAC, commonly present in personal care products, in cosmetic products can induce irritation and dose-dependent changes in the cell morphology. The cationic nature of BAC (it is a quaternary ammonium) suggests that one of the major targets of BAC in the cell may be mitochondria, the only intracellular compartment charged negatively. However, the influence of BAC on mitochondria has not been clearly understood. Here, the effects of BAC on energy parameters of rat liver mitochondria as well as on yeast cells were examined. BAC, being a "weaker" uncoupler, potently inhibited respiration in state 3, diminished the mitochondrial membrane potential, caused opening of the Ca2+/Pi-dependent pore, blocked ATP synthesis, and promoted H 2 O 2 production by mitochondria. BAC triggered oxidative stress and mitochondrial fragmentation in yeast cells. BAC-induced oxidative stress in mitochondria and yeast cells was almost totally prevented by the mitochondria-targeted antioxidant SkQ1; the protective effect of SkQ1 on mitochondrial fragmentation was only partial. Collectively, these data showed that BAC acts adversely on cell bioenergetics (especially on ATP synthesis) and mitochondrial dynamics and that its prooxidant effect can be partially prevented by the mitochondria-targeted antioxidant SkQ1.

Evaluation of Sub-Lethal Toxicity of Benzethonium Chloride in Cyprinus carpio Liver

“…In addition, the increased level of ROS affected the activity of LDH too (Figure 3b). This could be due to an increase of glycolysis rate versus Krebs cycle, consequent to a mitochondrial dysfunction induced by the exposure of fish to this cationic surfactant as previously was noticed [49,50].…”

Propagation of Mitochondria-Derived Reactive Oxygen Species within the Dipodascus magnusii Cells

“…It has been widely applied in treating a large number of pathologies related to oxidative stress [ 29 ]. Previously, we also showed that SkQ1 alleviated and even prevented prooxidant-induced oxidative stress in yeasts [ 77 , 79 , 80 ].…”

“…In contrast to cell cultures, they vigorously grow on a variety of simple, well-defined and inexpensive media, and respond quickly to various substances. Additionally, these giant cells normally contain freely moving mitochondria that are fragmented when oxidative stress is imposed [ 77 , 78 , 79 , 80 ]. If we add easy-to-visualize mitochondria in the cell and the possibility to explore a large number of individual cells using modern methods of flow cytometry and time-lapse microscopy, it becomes clear to us that D. magnusii cells are particularly suitable for revealing a cross-talk among oxidative stress, its propagation, and mitochondrial dynamics.…”

Lipophilic Cations Rescue the Growth of Yeast under the Conditions of Glycolysis Overflow

“…Possibly, the rescuing effect of BAC was via mitochondrial ATP synthesis inhibition due to its interference with mitochondrial respiratory complexes. Indeed, recently, it has been shown that BAC inhibits respiration and ATP production when added to intact mitochondria [ 24 ]. In agreement with this, we found that BAC induced an approximately 3-fold stimulation of the rate of glucose consumption ( Figure 3 ).…”