Propofol improves recovery from paraquat acute toxicity in vitro and in vivo

Ariyama, Jun; Shimada, Hiroki; Aono, Makoto; Tsuchida, Hidekazu; Hirai, Kei-Ichi

doi:10.1007/s001340051291

Cited by 19 publications

(8 citation statements)

References 22 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Yeh et al [61] documented that N ‐acetylcysteine, a precursor of glutathione and a free radical scavenger reduced paraquat‐induced toxicity and mortality in rats. Other antioxidants including propofol and trolox also were reported to improve the recovery from acute paraquat toxicity in mice [62].…”

Section: Discussionmentioning

confidence: 99%

Melatonin reduces mortality and oxidatively mediated hepatic and renal damage due to diquat treatment

Sun

Wei

et al. 2006

Journal of Pineal Research

View full text Add to dashboard Cite

The bipyridyl herbicide, diquat, is a potent prooxidant that generates superoxide anions through redox cycling in vivo. Exposure to elevated levels of this compound causes acute hepatic and renal toxicity as well as death in rodents. In the present study, we investigated whether melatonin, a free radical scavenger and antioxidant, could protect against diquat-induced hepatic and renal damage and whether the indole would improve survival of Kunming mice given a lethal dose of diquat. When mice were intraperitoneally (i.p.) given a single dose of diquat (50 mg/kg body weight), liver and kidney injuries were observed at 6 hr as indicated by elevated serum levels of both alanine aminotransferase (ALT) activity and blood urea nitrogen (BUN). In addition, lipid peroxidation levels in both liver and kidney showed significant increases as shown by elevated concentrations of F(2)-isoprostanes. The administration of melatonin (20 mg/kg) 30 min before the diquat injection resulted in a significant reduction in serum levels of ALT and BUN as well as hepatic and renal F(2)-isoprostanes levels. For the survival study, 75 mg/kg diquat was administered i.p. into mice to induce acute death. Without melatonin treatment, 10 of 23 (43.5%) mice died within 24 hr after diquat injection. Pretreatment with melatonin (20 mg/kg) 30 min prior to the injection of diquat and thereafter at 4-hr intervals until the end of the observation period (24 hr), reduced the death rate to two of 22 (9.1%) mice. Chi-squared test revealed a significant difference with P< or = 0.05. In conclusion, melatonin, a broad spectrum antioxidant, reduces hepatic and renal damage and lowers the death rate in diquat-treated mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Melatonin reduces mortality and oxidatively mediated hepatic and renal damage due to diquat treatment

Sun

Wei

et al. 2006

Journal of Pineal Research

View full text Add to dashboard Cite

show abstract

“…The effects of benzoquinone (BQ; 0.2 mM, Sigma-Aldrich) were evaluated after 10 min of incubation in BQadded medium. Intracellular H 2 O 2 production in HeLa cells by PQ was detected using 2Ј,7Ј-dichlorofluorescein-diacetate (DCFH; Molecular Probes) (17,18). Briefly, cells were pretreated with 1 mM PQ for 1 h at 37°C, and then the cells were incubated with 5 M DCFH for 20 min in the dark.…”

Section: Intracellular Ros Productionmentioning

confidence: 99%

Paraquat Toxicity Induced by Voltage-dependent Anion Channel 1 Acts as an NADH-dependent Oxidoreductase

Shimada

Hirai²,

Simamura

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Paraquat (PQ), a herbicide used worldwide, causes fatal injury to organs upon high dose ingestion. Treatments for PQ poisoning are unreliable, and numerous deaths have been attributed inappropriate usage of the agent. It is generally speculated that a microsomal drug-metabolizing enzyme system is responsible for PQ toxicity. However Paraquat (PQ 2 ; methyl viologen, 1,1Ј-dimethyl-4,4Ј-bipyridinium dichloride) is an effective herbicide used in more than 120 countries (1). Although it is classified as a low hazard compound, PQ is hazardous when used improperly and has been found responsible for thousands of deaths worldwide because of intentional overdose and high levels of occupational and accidental exposure especially in developing countries (1). Direct exposure to PQ causes severe irritation to the eyes and skin, and ingestion of concentrated products may result in fatal injury to lungs because of edema, hemorrhage, and subsequent fibrosis as well as damage to other organs (2). Additionally, PQ has emerged as a risk factor for Parkinson disease (3). The acute toxicity of PQ in mammals is mediated by reactive oxygen species (ROS) produced by a cyclic oxidation-reduction reaction (4). It is generally speculated that NADPH-cytochrome P450 reductase in microsomal drug-metabolizing enzyme systems is responsible for the production of ROS (5). However, we previously observed that the initial ultrastructural alterations associated with PQ exposure occurred only in mitochondria and not in the endoplasmic reticulum in pulmonary cells in vivo (6) and in vitro (7). In addition, several reports have suggested the cytotoxicity of PQ via mitochondrial dysfunction (8 -10). Despite the development of a number of treatments for PQ poisoning, the efficacy and reliability of currently available treatments have remained limited because of an insufficient understanding of PQ cytotoxicity (2).We recently discovered that active NADH-dependent oxidoreductase located on the mitochondrial outer membrane reduced PQ to a radical form that spontaneously formed superoxide anion (O 2 . ) and destroyed mitochondria (11-13). Furthermore, we demonstrated that 1) PQ was initially metabolized to monopyridone in the cytosol and subsequently hydroxylated by the microsomes and 2) the induction of drugmetabolizing enzymes and the administration of a ROS scavenger reduced PQ toxicity in mice (11,14). These results indicate that the mitochondrial system, not the microsomal system, is responsible for PQ toxicity. We verified that enzymes in the electron transport chain and NADH-cytochrome b 5 reductase, an NADH-dependent oxidoreductase in the outer membrane, were not involved in this reaction (11,12). A voltage-dependent anion channel (VDAC), an abundant pore-forming protein in the outer membrane, exerts numerous physiological functions as a channel; it regulates both the metabolite flux of mitochondria and transmembrane potential, and plays a role in apoptosis. Recently, it was reported that NADH regulates VDAC func-*

show abstract

“…It is important to be able to provide safe anesthesia with neuroprotective potential in such cases. Propofol post-conditioning has shown protection against hypoxic injury and paraquat toxicity in in vitro and in vivo conditions [1,2]. Previous studies have indicated that some anesthetics have neuroprotective effects, given their ability to suppress cerebral metabolic rate, antagonize glutamate-mediated excitotoxicity, and enhance inhibitory synaptic transmission [3–6].…”

Section: Introductionmentioning

confidence: 99%

Propofol Increases Expression of Basic Fibroblast Growth Factor After Transient Cerebral Ischemia in Rats

et al. 2012

View full text Add to dashboard Cite

Anesthetics such as propofol can provide neuroprotective effects against cerebral ischemia. However, the underlying mechanism of this beneficial effect is not clear. Therefore, we subjected male Sprague-Dawley rats to 2 h of middle cerebral artery occlusion and investigated how post-ischemic administration of propofol affected neurologic outcome and the expression of basic fibroblast growth factor (bFGF). After 2 h of ischemia, just before reperfusion, the animals were randomly assigned to receive either propofol (20 mg•kg−1•h−1) or vehicle (10% intralipid, 2 ml•kg−1•h−1) intravenously for 4 h. Neurologic scores, infarct volume, and brain water content were measured at different time points after reperfusion. mRNA level of bFGF was measured by real-time PCR, and the protein expression level of bFGF was analyzed by immunohistochemistry and Western blot. At 6 h, 24 h, 72 h, and 7 days of reperfusion, infarct volume was significantly reduced in the propofol-treated group compared to that in the vehicle-treated group (all P<0.05). Propofol post-treatment also attenuated brain water content at 24 and 72 h and reduced neurologic deficit score at 72 h and 7 days of reperfusion (all P<0.05). Additionally, in the peri-infarct area, bFGF mRNA and protein expression were elevated at 6, 24, and 72 h of reperfusion compared to that in the vehicle-treated group (all P<0.05). These results show that post-ischemic administration of propofol provides neural protection from cerebral ischemia-reperfusion injury. This protection may be related to an early increase in the expression of bFGF.

show abstract

Propofol improves recovery from paraquat acute toxicity in vitro and in vivo

Abstract: Post i.v. injection of propofol is protective against paraquat-induced damage. Propofol can be given during mechanical ventilatory support after paraquat poisoning.

Cited by 19 publications

References 22 publications

Melatonin reduces mortality and oxidatively mediated hepatic and renal damage due to diquat treatment

Melatonin reduces mortality and oxidatively mediated hepatic and renal damage due to diquat treatment

Paraquat Toxicity Induced by Voltage-dependent Anion Channel 1 Acts as an NADH-dependent Oxidoreductase

Propofol Increases Expression of Basic Fibroblast Growth Factor After Transient Cerebral Ischemia in Rats

Contact Info

Product

Resources

About