Inhibition of canine and feline alcohol dehydrogenase activity by fomepizole

Connally, Heather E.; Hamar, Dwayne W.; Thrall, Mary Anna

doi:10.2460/ajvr.2000.61.450

Cited by 24 publications

(22 citation statements)

References 26 publications

(13 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lysate from untreated NIH3T3 cells or NIH3T3 cells that were incubated with 50 µM 4MP for 48 h or purified equine ADH (Sigma) plus or minus 50 µM 4MP was assayed for ADH activity. The conversion of ethanol to acetaldehyde at 30°C was measured by following the formation of reduced NADH from oxidized NAD + at 340 nm by use of a spectrophotometer (16). The final reaction volume was 1.5 mL, and reactions were carried out in 0.5 M TrisHCl, pH 7.5, containing 2.8 mM NAD + , 1 mg protein from cell lysate or 25 µg purified equine ADH, and/or 50 µM 4MP.…”

Section: Methodsmentioning

confidence: 99%

“…Reactions were initiated by the addition of 5 mM ethanol. To determine whether 50 µM 4MP is sufficient to inhibit ADH activity, purified equine ADH was incubated with 50 µM 4MP for 5 m at 30°C prior to the addition of ethanol (16) or lysate from cells that were incubated with 50 µM 4MP for 48 h. ADH activity was calculated using the extinction coefficient for NADH at 340 nm, 6220 M −1 cm −1 . Activity was calculated as mol of NADH formed per min per mg protein.…”

Section: Methodsmentioning

confidence: 99%

“…To determine whether inhibition of ADH would alter the ability of GGOH to maintain Rap1 isoprenylation in the presence of LOV, NIH3T3 cells were incubated concurrently with LOV, 4MP, and GGOH for 24 h. Figure 5B is a representative Western blot, demonstrating that inhibition of ADH does not inhibit the ability of GGOH to maintain Rap1 isoprenylation in the presence of LOV. An in vitro assay was used to confirm that 50 µM 4MP is sufficient to inhibit ADH activity in NIH3T3 cells as described in the methods (16). The activity of ADH in lysate from untreated NIH3T3 cells was 547.8 pmol/min/mg total protein, which was decreased to 16.1 pmol/min/mg protein in lysate from NIH3T3 cells that were incubated with 50 µM 4MP prior to lysing.…”

Section: The Effects Of Lov Concurrently With Foh or Ggoh On Protein mentioning

confidence: 99%

See 2 more Smart Citations

Isoprenoid alcohols restore protein isoprenylation in a time‐dependent manner independent of protein synthesis

Ownby

Hohl

2003

Lipids

View full text Add to dashboard Cite

Mevalonic acid derivatives are required for the isoprenylation of a variety of growth-regulating proteins. Treatment of NIH3T3 cells with lovastatin (LOV), an HMG-CoA reductase inhibitor, depletes cells of these derivatives and impairs isoprenylation of RAS and RAS-related proteins. In LOV-treated cells, farnesol (FOH) and geranylgeraniol (GGOH) restore RAS and Rap1 isoprenylation, respectively. In this study, we further characterize the manner in which these isoprenoid alcohols are utilized for protein isoprenylation. Over a 48-h time span, FOH is unable to maintain RAS isoprenylation in the continuing presence of LOV, whereas GGOH is able to maintain Rap1 isoprenylation in the presence of LOV at all times tested. When cells are pretreated with LOV, the ability of both FOH and GGOH to restore protein isoprenylation is time dependent; as the LOV pretreatment time increases, the time required for FOH and GGOH to restore isoprenylation also increases. Despite this time dependence, the ability of FOH and GGOH to restore protein isoprenylation is not dependent on new protein synthesis and does not require alcohol dehydrogenase. These data support the existence of and further characterize the isoprenoid shunt, a novel metabolic pathway that utilizes FOH and GGOH for protein isoprenylation. The enzymes of the isoprenoid shunt are constitutively expressed, their activity may be modulated by isoprenoid depletion, and they are differentially regulated.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: The Effects Of Lov Concurrently With Foh or Ggoh On Protein mentioning

confidence: 99%

See 1 more Smart Citation

Isoprenoid alcohols restore protein isoprenylation in a time‐dependent manner independent of protein synthesis

Ownby

Hohl

2003

Lipids

View full text Add to dashboard Cite

show abstract

“…Alcohol dehydrogenase is known to have greater affinity for ethanol than for EG; so, if given in time, ethanol is an effective antidote to prevent metabolism of EG. 21 However, ethanol is associated with increased side effects such as worsened CNS depression, metabolic acidosis and hyperosmolality. 18 …”

Section: Ethanolmentioning

confidence: 99%

“…However, studies have shown efficacy of this drug when given at much higher doses than those administered to dogs. 18,19,21 The recommended dose for cats is 125 mg/kg IV followed by 31.25 mg/kg IV at…”

Section: Fomepizolementioning

confidence: 99%

Feline acute kidney injury

Monaghan

Nolan²,

Labato

2012

Journal of Feline Medicine and Surgery

View full text Add to dashboard Cite

Practical relevance: Acute kidney injury (AKI) is a frequently recognized disease process in cats that requires immediate and aggressive intervention. A thorough understanding of the pathophysiologic processes underlying AKI and familiarity with the most common etiologies are essential for providing the most effective and timely therapy. Possessing this knowledge will also allow a more accurate prognosis to be given, and afford the best chance of a favorable outcome. Clinical challenges:Feline patients often present with vague signs of AKI, which may delay treatment and adversely affect the prognosis. Their response to injury and treatment is often different to that of other species.Audience: This two-part review article is directed at small animal practitioners as well as specialists. Part 1 reviews mechanisms underlying AKI in the cat, as well as etiologies and treatments related to some specific causes of AKI. New terminology -and a new emphasisAcute kidney injury (AKI) is a relatively new term in the nephrology literature that largely replaces the use of 'acute renal failure' (ARF). Originally introduced in the human literature, AKI allows for greater stratification of cases with regard to severity and prognosis. By suggesting that a patient has injury, rather than failure, one can recognize the potential for earlier treatment and recovery. In human medicine, the older term 'ARF' refers only to patients requiring renal replacement therapy (RRT). Additionally, the more common term 'kidney', rather than 'renal', facilitates communication with and understanding by clients of AKI. The incidence of AKI in cats is not known, but it is not uncommon and can be caused by a variety of different insults. A uniform definition for AKI does not exist in the veterinary literature and varies among publications. Generally accepted criteria include an abrupt reduction in kidney function resulting in alterations in glomerular filtration, urine production and tubular function. These alterations result in an inability to maintain fluid, electrolyte and acid-base balance, and may lead to azotemia. PathophysiologyThe pathophysiology of AKI is complex, but can be described by four stages: initiation, extension, maintenance and recovery.

show abstract

Treatment

Poppenga¹

2004

Clinical Veterinary Toxicology

View full text Add to dashboard Cite

Inhibition of canine and feline alcohol dehydrogenase activity by fomepizole

Cited by 24 publications

References 26 publications

Isoprenoid alcohols restore protein isoprenylation in a time‐dependent manner independent of protein synthesis

Isoprenoid alcohols restore protein isoprenylation in a time‐dependent manner independent of protein synthesis

Feline acute kidney injury

Treatment

Contact Info

Product

Resources

About