Synergism of ochratoxin B and calcium-channel antagonist verapamil caused mitochondrial dysfunction

Abstract

We examined the mechanism by which the ochratoxin B induced interaction with calcium-channel antagonist verapamil and mitochondrial dysfunction of the rat trachea in vitro experiment. The tracheas were cut into 2–3 mm wide rings and suspended in a tissue bath. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. Verapamil (1 × 10⁻⁶ M) produced a concentration-dependent contraction response in rat’s tracheal rings pre-contracted by acetylcholine. Incubation of rat’s tracheal rings with the ochratoxin B significantly potentiated the contraction responses of verapamil. Verapamil and OTB accelerate the overloading of Ca²⁺ in tracheal smooth muscle contributes the tissue toxicity as shown in electron microscopy and mitochondrial enzymes, through a mechanism that could involve perturbations of Ca²⁺ homeostasis. These results proved that ochratoxin B is a potential vasoconstrictor mycotoxin with the presence of calcium-channel antagonist. In conclusion, disturbance of Ca²⁺ homeostasis caused by OTA and plays a significant role in produces toxicity through mitochondrial enzyme inhibition.

• Ca²⁺ channel blocker
• intercellular Ca²⁺
• ochratoxin B

Acknowledgements

The authors sincerely thank Defence Research Laboratory (DRDO) for providing facilities and financial assistance for completion of this investigation.