Heavy Ethanol Intoxication Increases Proinflammatory Cytokines and Aggravates Hemorrhagic Shock-Induced Organ Damage in Rats

Hu, Tsung‐Ming; Lee, Ru‐Ping; Lee, Chung‐Jen; Subeq, Yi‐Maun; Lin, Ning; Hsu, Bang‐Gee

doi:10.1155/2013/121786

Cited by 14 publications

(25 citation statements)

References 32 publications

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“…27 Also noteworthy are data associating alcohol use with increased severity of injury 28 and decreased physiologic ability to compensate for shock. 29 Moreover, alcohol-related deaths make up a large share of prehospital injury mortality, which are impossible to assess in hospital-based studies such as ours. 30 Alcohol may increase the risk of being injured and may exogenously decrease the GCS score, but it remains unclear how it impacts outcomes in patients with TBI.…”

Section: Discussionmentioning

confidence: 81%

Mortality-Associated Characteristics of Patients with Traumatic Brain Injury at the University Teaching Hospital of Kigali, Rwanda

et al. 2017

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OBJECTIVE Traumatic brain injury (TBI) is a leading cause of death and disability. Patients with TBI in low and middle-income countries have worse outcomes than patients in high-income countries. We evaluated important clinical indicators associated with mortality for patients with TBI at University Teaching Hospital of Kigali, Kigali, Rwanda. METHODS A prospective consecutive sampling of patients with TBI presenting to University Teaching Hospital of Kigali Accident and Emergency Department was screened for inclusion criteria: reported head trauma, alteration in consciousness, headache, and visible head trauma. Exclusion criteria were age <10 years, >48 hours after injury, and repeat visit. Data were assessed for association with death using logistic regression. Significant variables were included in a multivariate logistic regression model and refined via backward elimination. RESULTS Between October 7, 2013, and April 6, 2014, 684 patients were enrolled; 14 (2%) were excluded because of incomplete data. Of patients, 81% were male with mean age of 31 years (range, 10–89 years; SD 11.8). Most patients (80%) had mild TBI (Glasgow Coma Scale [GCS] score 13–15); 10% had moderate (GCS score 9–12) and 10% had severe (GCS score 3–8) TBI. Multivariate logistic regression determined that GCS score <13, hypoxia, bradycardia, tachycardia, and age >50 years were significantly associated with death. CONCLUSIONS GCS score <13, hypoxia, bradycardia, tachycardia, and age >50 years were associated with mortality. These findings inform future research that may guide clinicians in prioritizing care for patients at highest risk of mortality.

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Section: Discussionmentioning

confidence: 81%

Mortality-Associated Characteristics of Patients with Traumatic Brain Injury at the University Teaching Hospital of Kigali, Rwanda

et al. 2017

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“…After the operation, animals were placed in conscious rat metabolic cages (Shingshieying Instruments, Hualien, Taiwan). The rats were awakened soon after the operations, and rhabdomyolysis was induced by glycerol injection 24 h later while they were conscious, as previously described 11 , 16 , 17 .…”

Section: Methodsmentioning

confidence: 99%

“…Acute alcohol intoxication is a clinically harmful condition that can cause traumatic injuries, negatively affect the function of multiple organs, and lead to increased rates of morbidity and mortality 10 , 11 . Although moderate alcohol consumption is cardio-protective, heavy alcohol consumption increases the risk of renal disease because it negatively affects endothelial function, which increases the risk for renal damage 12 , 13 .…”

Section: Introductionmentioning

confidence: 99%

“…Thus, alcohol-fed rats develop significant renal dysfunction, interstitial edema, and renal hypertrophy 14 , and increased levels of oxidized proteins and lipids in the kidneys 13 , 15 . A recent study reported that rats given intravenous ethanol before induction of hemorrhagic shock had greatly aggravated renal tubular necrosis scores and elevated serum levels of pro-inflammatory cytokines 11 . Rhabdomyolysis can both cause renal damage.…”

Section: Introductionmentioning

confidence: 99%

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Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats

Tsai¹,

Lee²,

Subeq³

et al. 2017

Int. J. Med. Sci.

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Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects.

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“…Genetic differences (alcohol-preferring [P] vs –nonpreferring [NP] rats) in cAMP second messenger systems are associated with differences in a propensity for alcohol abuse (Pandey et al 1999). Similarly, chronic alcohol drinking reduces cellular cAMP levels (Gobejishvili et al 2008) and increases immune signaling and inflammatory response (Fernandez-Lizarbe et al 2009; Gobejishvili et al 2008; Hu et al 2013; Qin et al 2008). Alcohol and drug dependence are associated with complex interactions between immune and neural signaling, stress-associated activity (e.g.…”

Section: Introductionmentioning

confidence: 99%

Reduction of alcohol drinking of alcohol-preferring (P) and high-alcohol drinking (HAD1) rats by targeting phosphodiesterase-4 (PDE4)

et al. 2015

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Rationale Phosphodiesterase-4 (PDE4) and neuroimmune signaling have been posited to regulate alcohol drinking. Objectives This study evaluated the involvement of PDE4 and Il22ra2 on ethanol (EtOH) intake by alcohol-preferring (P) and high-alcohol drinking (HAD1) rats. Methods Exp 1 determined the dose-response effects of PDE4 inhibitors, rolipram and Ro 20-1724, on 2h/day free-choice EtOH intake by adult P and HAD1 rats. Exps 2–3 examined the effects of repeated administration with the PDE4 inhibitors on EtOH or sucrose intake, and locomotor behavior. Exp 4 determined Pde4-associated gene expression differences in subregions of the extended amygdala, between high- and low-alcohol-consuming rat lines. Exp 5 evaluated the effects of infusing short hairpin RNA to knock down Il22ra2 in the nucleus accumbens (NAc) shell on 24h free-choice EtOH drinking by P rats. Results Administration of rolipram or Ro 20-1724 reduced EtOH intake by P rats; Ro 20-1724 reduced EtOH intake by HAD1 rats. Repeated rolipram or Ro 20-1724 exposure reduced EtOH intake by P and HAD1 rats. PDE4 inhibition induced motor impairment during the first hour of EtOH intake by P rats. Higher gene expression levels for PDE4A were found in the NAc shell of P vs. NP rats. ShRNAs targeting Il22ra2 in the NAc shell significantly reduced chronic EtOH intake. Conclusions PDE4 and neuroinflammatory/immune signaling pathways could represent molecular targets for the treatment of alcohol use disorders, in genetically predisposed subjects. This study underscores the importance of testing compounds over multiple days and rat lines when determining efficacy to disrupt excessive alcohol intake.

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Heavy Ethanol Intoxication Increases Proinflammatory Cytokines and Aggravates Hemorrhagic Shock-Induced Organ Damage in Rats

Cited by 14 publications

References 32 publications

Mortality-Associated Characteristics of Patients with Traumatic Brain Injury at the University Teaching Hospital of Kigali, Rwanda

Mortality-Associated Characteristics of Patients with Traumatic Brain Injury at the University Teaching Hospital of Kigali, Rwanda

Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats

Reduction of alcohol drinking of alcohol-preferring (P) and high-alcohol drinking (HAD1) rats by targeting phosphodiesterase-4 (PDE4)

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