Changes of mitochondrial ultrastructures and function in central nervous tissue of hens treated with tri-ortho-cresyl phosphate (TOCP)

Abstract

<jats:p> Tri-ortho-cresyl phosphate (TOCP), an organophosphorus ester, is capable of producing organophosphorus ester-induced delayed neurotoxicity (OPIDN) in humans and sensitive animals. The mechanism of OPIDN has not been fully understood. The present study has been designed to evaluate the role of mitochondrial dysfunctions in the development of OPIDN. Adult hens were treated with 750 mg/kg·bw TOCP by gavage and control hens were given an equivalent volume of corn oil. On day 1, 5, 15, 21 post-dosing, respectively, hens were anesthetized by intraperitoneal injection of sodium pentobarbital and perfused with 4% paraformaldehyde. The cerebral cortex cinerea and the ventral horn of lumbar spinal cord were dissected for electron microscopy. Another batch of hens were randomly divided into three experimental groups and control group. Hens in experimental groups were, respectively, given 185, 375, 750 mg/kg·bw TOCP orally and control group received solvent. After 1, 5, 15, 21 days of administration, they were sacrificed and the cerebrum and spinal cord dissected for the determination of the mitochondrial permeability transition (MPT), membrane potential (Δψ<jats:sub> m</jats:sub>) and the activity of succinate dehydrogenase. Structural changes of mitochondria were observed in hens’ nervous tissues, including vacuolation and fission, which increased with time post-dosing. MPT was increased in both the cerebrum and spinal cord, with the most noticeable increase in the spinal cord. Δψ<jats:sub>m</jats:sub> was decreased in both the cerebrum and spinal cord, although there was no significant difference in the three treated groups and control group. The activity of mitochondrial succinate dehydrogenase assayed by methyl thiazolyl tetrazolium (MTT) reduction also confirmed mitochondrial dysfunctions following development of OPIDN. The results suggested mitochondrial dysfunction might partly account for the development of OPIDN induced by TOCP. </jats:p>

Lactobacillus plantarum NDC 75017 alleviates the learning and memory ability in aging rats by reducing mitochondrial dysfunction

“…The targeted accumulation of ROS damages the mitochondria, which are more sensitive and vulnerable to oxidative stress than other organelles in cells due to their structural and functional characteristics (6). The decrease in mitochondrial function and the increase in mitochondrial DNA damage suggests that the progressive accumulation of oxidative DNA damage is a contributing factor to cell apoptosis or necrosis, with the generation of more ROS during aging (10,20,28,29). Chronic administration of D-gal has been widely used to mimic the process of brain aging.…”

“…At present, mitochondrial Ca 2+ homeostasis is the center of widespread interest in scientific studies due to its modulatory role in numerous physiological processes and its involvement in cell death (6,28,29). Ca 2+ uptake and release from the mitochondrial membrane via a variety of mechanisms control the local regulation of intracellular Ca 2+ concentration.…”

“…Ca 2+ uptake and release from the mitochondrial membrane via a variety of mechanisms control the local regulation of intracellular Ca 2+ concentration. The mitochondrial Ca 2+ dysfunction can cause MPT pore opening, leading to a change in the Δψ m and resulting in mitochondrial swelling and dysfunction, and even cell death (28). It has been demonstrated that injecting rodents with D-gal for 6–10 weeks induces aging, affecting mitochondrial bioenergetics.…”

“…The methods and procedures utilized in the present study were identical to those of a previous study (28). Briefly, 0.02 ml MTT (0.1 mg/ml) was added to the mitochondrial solution containing 60 μg protein.…”

“…Mitochondria were isolated from the cerebral cortices of the rats through homogenization and differential centrifugation according to the methods performed in a previous study (28). The protein content of the isolated mitochondria samples was determined using the Bradford protein assay.…”