grape seed extract posioning

[malernee]

: J Am Vet Med Assoc 2001 Aug 15;219(4):434, 436 Related Articles,Links

Comment on:
J Am Vet Med Assoc. 2001 May 15;218(10):1555-6.
More information on grape or raisin toxicosis.

Singleton VL.

Publication Types:
Comment
Letter
PMID: 11518164 [PubMed - indexed for MEDLINE]

Notes
Renal Failure Associated with Ingestion of Grapes or Raisins in Dogs
J Am Vet Med Assoc 218[10]:1555-1556 May 15'01 Letter 0 Refs

Sharon Gwaltney-Brant, DVM, PhD; Judy K. Holding, DVM; Caroline W Donaldson, DVM; Paul A. Eubig, DVM; Safdar A. Khan, DVM, PhD, DABVT
ASPCA Animal Poison Control Center (APCC), Urbana, IL
"A review of cases from the ASPCA Animal Poison Control Center computerized database revealed 10 dogs with evidence of ingestion of large amounts of either raisins (five dogs) or grapes (five dogs). ... The estimated amount of raisins or grapes was known in four dogs and ranged between 9 oz and 2 lb (0.41 and 1.1 oz/kg)...Two dogs died and three were euthanatized because of poor response to treatment. Five dogs recovered with aggressive treatment, which lasted up to three weeks in some cases. Treatments included fluids administered IV, furosemide, dopamine, and mannitol. One dog that underwent peritoneal dialysis for several days recovered completely. ... Histopathologic findings in one dog were consistent with mild renal tubular damage and metastatic mineralization of numerous tissues, but the pathologist judged the severity of these lesions to be insufficient to explain the severity of the dog's clinical illness To date, results of screening for various contaminants (e.g., heavy metals, mycotoxins) have been negative, although further results are pending.... Until more data are available, we currently recommend that ingestion of large amounts of grapes or raisins in dogs be managed aggressively. Decontamination measures (e.g., emesis, lavage, activated charcoal) should be taken after recent ingestions. Fluids should be administered for a minimum of 48 hours and serum chemistry values monitored for 72 hours for the development of acute renal failure. The cause of acute renal failure in these dogs is unknown. Some of the possibilities include contamination with mold toxins (e.g., ochratoxins); presence of high amounts of vitamin D, or similar compounds; contamination with pesticides, heavy metals, or other environmental toxins; or some as yet unknown intrinsic toxin(s)..."
****
Recently there has been a lot of talk about grape and raisin toxicity in dogs. What is known:

Dogs affected will vomit with a few hours of eating a large
amount of either raisins or grapes. Then within 12-24 hours they may become anorexic and have diarrhea. Dogs will develop kidney damage in the first day after exposure. Severely elevated calcium and calcium/phosphorus levels occur in toxicity. Acute kidney tubular damage via cell apoptosis (death) occurs.

What is most likely known:
Pharmacological and physiological conclusions indicate:

1) Rapid absorption of grapes and grape seed extract
occurs oral ingestion.
2) Being a fructose sugar..it is quickly eliminated
through the kidneys where is reaches very high tissue
levels.
3)Grape extract and grape seed extract cause
the mitochondrial transition pore membrane to
open and allow calcium influx into the mitochondria.
This causes mitochondria to stop functioning...
4) When the mitochondria stops functioning...
then this activates cell death via the release
of cytochrome C which then activates the caspase
pathway ending with cell death via apoptosis
(not necrosis).

Questions to be answered!
Why do grapes cause this and not other fruits
and/or other flavanoids... why is it just the
grade seed extract?

Why do dogs suffer from renal damage and not
humans or many other species etc.

[malernee]

A study in Cardiovascular Toxicology indicated that higher doses of grape seed proanthocyanidin extract may cause apoptotic cell injury and subsequent induction of reactive oxygen species generation.


[Shao ZH et al. Grape seed proanthocyanidins induce pro-oxidant toxicity in cardiomyocytes. Cardiovascular Toxicology. 2003;3(4):331-339.]

Through an as yet undetermined mechanism, researchers have found that combining Vitamin C and grape-seed polyphenols results in blood pressure elevations. [Ward NC et al. The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens. 2005;23(2):427-434.

Finally, as with so many other commonly administered herbs, there is a possibility of affecting cytochrome enzymes systems and as such, pharmacokinetics of co-administered medications, although the impact of grape seed extract in vivo remains as yet undetermined. [Nishikawa M et al. Effects of continuous ingestion of green tea or grape seed extracts on the pharmacokinetics of midazolam. Drug Metab Pharmacokin. 2004;19(4):280-289.]