Lead/ethanol interactions II: Pharmacokinetics

Nation, Jack R.; Burkey, Robert T.; Grover, Cathy A.

doi:10.1016/0741-8329(93)90021-f

Cited by 16 publications

(23 citation statements)

References 20 publications

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“…injection was estimated based on a previous study that evaluated the pharmacokinetic profile of a 3g/kg i.p. alcohol injection in rats [23].…”

Section: Blood Alcohol Determinationmentioning

confidence: 99%

“…Forty-eight adult (450 g) male Sprague-Dawley rats (Harlan Corp., Indianapolis, IN) were randomly assigned in groups of eight to one of six treatment groups: 1) control (C) saline-injected: 2) alcohol-treated (A) This dose was chosen to achieve peak BACs of approximately 300 mg/dl [23]. Alcohol injections were given starting at 9:00 a.m., 3 days/week.…”

Section: Binge Alcohol Treatmentmentioning

confidence: 99%

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Vitamin D and ibandronate prevent cancellous bone loss associated with binge alcohol treatment in male rats

Wezeman¹,

Juknelis²,

Himes³

et al. 2007

Bone

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Decreased bone mass and bone strength can result from excess alcohol consumption in humans and alcohol treatment in the rat. Although the specific mechanism is unknown, the damaging effects of alcohol abuse modulate the bone remodeling cycle and increase bone turnover. Chronic alcohol consumption models have shown an inhibition of bone formation. We previously reported that binge alcohol treatment increases bone resorption and that alcohol-induced damage can be prevented by treatments with intermittent parathyroid hormone and bisphosphonates. In this study we hypothesized that an effective dose of vitamin D (cholecalciferol) or a single dose of ibandronate would prevent bone loss caused by binge alcohol treatment in male rats. Forty-eight adult (450 gram) male Sprague-Dawley rats were randomly assigned to 6 treatment groups (n=8): a) saline, i.p.3 days/ week (C); b) binge alcohol, 3g/kg i.p., 3 days/week (A); c) vitamin D, 5,000 IU/kg daily s.c., (D); d) binge alcohol and vitamin D (AD); e) e) ibandronate, (120 ug, given as a single i.p. injection (I); f) alcohol and ibandronate (AI). After 4 weeks of treatment proximal tibia and L3 and L4 vertebrae were analyzed for bone mineral density (BMD) by quantitative computerized tomography and compressive strength-to-failure using an Instron materials testing machine. Type-I collagen crosslinked c-telopeptide, calcium, and 25-OH vitamin D levels were measured in serum collected at the time of sacrifice. Binge alcohol significantly decreased cancellous BMD by 58% in tibia and 23% in lumbar spine (p < 0.05). Binge alcohol treatment decreased L3 and L4 compressive strength-tofailure by 21% (p <.05). Treatment with vitamin D at 5,000 IU/kg/day prevented alcohol-induced bone loss, significantly increasing both tibial and vertebral cancellous BMD values (161% increase in tibia and 40% increase in vertebra, respectively, p < 0.05) compared to alcohol alone groups. Pretreatment with the single dose of 120 ug ibandronate prevented alcohol-induced bone loss, increasing cancellous BMD by 186% in tibiae and by 46% in vertebrae compared to the alcohol alone group (p < 0.05). In summary, binge alcohol-induced tibial and vertebral bone loss can be prevented using an effective dose of vitamin D or a single dose of ibandronate even during high blood alcohol concentrations that have been shown to impair osteoblast functions and increase bone resorption.

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“…injection was estimated based on a previous study that evaluated the pharmacokinetic profile of a 3g/kg i.p. alcohol injection in rats [23].…”

Section: Blood Alcohol Determinationmentioning

confidence: 99%

Section: Binge Alcohol Treatmentmentioning

confidence: 99%

Vitamin D and ibandronate prevent cancellous bone loss associated with binge alcohol treatment in male rats

Wezeman¹,

Juknelis²,

Himes³

et al. 2007

Bone

View full text Add to dashboard Cite

show abstract

“…An IP dose of 3 g/kg was chosen to produce peak blood alcohol concentrations of approximately 300 mg/dL (Nation et al, 1993). A once daily treatment regime was chosen to avoid alcohol withdrawal symptoms that can occur when high doses of alcohol are administered twice daily (Penland et al, 2001).…”

Section: Binge Alcohol Exposure Model Systemmentioning

confidence: 99%

“…ethanol/saline solution at a dose of 3 g/kg. This dose was chosen to achieve peak BAC's of approximately 300 mg/dL (Nation et al, 1993). Alcohol injections were given starting at 9:00 AM, 4 days/week.…”

Section: Binge Alcohol Model Systemmentioning

confidence: 99%

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The Effects of Binge Alcohol Exposure on Bone Resorption and Biomechanical and Structural Properties are Offset by Concurrent Bisphosphonate Treatment

Callaci

Juknelis

Patwardhan

et al. 2004

Alcoholism Clin & Exp Res

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Background-Chronic alcohol consumption reduces bone mass and strength, increasing fracture risk for alcohol abusers. Mechanisms underlying this vulnerability involve modulation of bone remodeling. Direct effects of alcohol on bone formation have been documented; those on bone resorption are less well studied. Skeletal effects of exposure to high blood alcohol concentrations (BAC's) attained during binge drinking have not been studied. We examined the effects of repeated binge-like alcohol treatment on bone resorption, bone mineral density and vertebral compressive strength in adult male rats treated with the aminobisphosphonate, risedronate.

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Binge Alcohol-Induced Bone Damage is Accompanied by Differential Expression of Bone Remodeling-Related Genes in Rat Vertebral Bone

et al. 2009

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Binge alcohol-related bone damage is prevented by concurrent administration of bisphosphonates, suggesting an activation of bone resorption with patterned alcohol exposure. Although chronic alcohol abuse is known to cause osteopenia, little is known about the effects of binge drinking on bone metabolism. We examined the effects of binge alcohol exposure on the relationship between bone damage and modulation of bone remodeling-specific gene expression profiles. Our hypothesis was that bone damage observed in young adult rats after binge alcohol exposure is associated with differential expression of bone remodeling-related gene expression. We further hypothesized that this differential gene expression specific to bone remodeling (bone resorption or formation related) would be influenced by the duration of binge alcohol exposure. Binge alcohol (3 g/kg, i.p.) was administered on 3 consecutive days each week, for 1 or 4 weeks, to adult male rats. Matched control animals were injected with an equal volume of isotonic saline. Lumbar vertebrae, L4-5, were analyzed for the presence of bone damage by quantitative computed tomography and compressive strength analysis. Total RNA was isolated from an adjacent vertebrae (L3), and whole transcriptome gene expression data were obtained for each sample. The expression levels of a subset of bone formation and resorption-associated differentially expressed genes were validated by quantitative reverse transcriptase-polymerase chain reaction. Bone loss was not observed after 1 week of treatment but was observed after four binge alcohol cycles with a 23% decrease in cancellous bone mineral density and 17% decrease in vertebral compressive strength compared with control values (P < 0.05). We observed that the duration of binge alcohol treatment influenced the modulation of expression profiles for genes that regulate the bone formation process. The expression of key bone formation-related marker genes such as osteocalcin and alkaline phosphatase were significantly reduced (P < 0.05) after acute binge alcohol exposure, and expression of regulators of osteoblast activity such as bone morphogenetic proteins and parathyroid hormone receptor displayed significantly (P < 0.05) decreased differential expression. The expression of sclerostin, a key canonical Wnt inhibitory protein, was significantly increased after acute binge alcohol treatment. The expression of important regulators of osteoclast maturation and activity such as NF-κβ (nuclear factor κβ) ligand (RANKL) and interleukin-6 were significantly increased (P < 0.05) by binge alcohol, and osteoprotegerin levels were significantly decreased (P < 0.05) in vertebral bone. These results show that expression patterns of several key bone remodeling genes are significantly perturbed by binge alcohol treatment, suggesting that perturbation of gene expression associated with bone remodeling may be one mechanism contributing to the disruption of bone mass homeostasis and subsequent bone loss observed after binge alcohol exposure in rode...

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Lead/ethanol interactions II: Pharmacokinetics

Cited by 16 publications

References 20 publications

Vitamin D and ibandronate prevent cancellous bone loss associated with binge alcohol treatment in male rats

Vitamin D and ibandronate prevent cancellous bone loss associated with binge alcohol treatment in male rats

The Effects of Binge Alcohol Exposure on Bone Resorption and Biomechanical and Structural Properties are Offset by Concurrent Bisphosphonate Treatment

Binge Alcohol-Induced Bone Damage is Accompanied by Differential Expression of Bone Remodeling-Related Genes in Rat Vertebral Bone

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