Phenobarbital

1. Phenobarbital shortens lifespan in rats (approximately 20%).

   “daily administration of therapeutic-like doses of phenobarbital to male and female rat pups during the first postpartum week reduced life expectancy by approximately 20%”

   Animalsfirst postpartum week

   Neonatal phenobarbital imprints overexpression of cytochromes P450 with associated increase in tumorigenesis and reduced life span

   FASEB journal : official publication of the Federation of American Societies for Experimental Biology·5 Jan 2005

2. Phenobarbital has no effect on lifespan in rats.

   “registered only in females but not in males”

   Animalsfirst 3 days of life35 mg/kg3 daysmales

   Changes in the longevity of rats under the influence of enzyme imprinting by phenobarbital

   Zhurnal obshchei biologii·1 Jan 2000

3. Phenobarbital extends lifespan in rats.

   “leading to increase in average lifespan of rats”

   Animalsfirst 3 days of life35 mg/kg3 daysfemales

   Changes in the longevity of rats under the influence of enzyme imprinting by phenobarbital

   Zhurnal obshchei biologii·1 Jan 2000

4. Phenobarbital has no effect on lifespan in rats (did not change).

   “A mean lifespan of experimental female rats increased by 17.5% compared to the level of control animals and did not change in male rats.”

   Animalsmale rats3.5 mg/100 g body weight per dayduring 1-3 days after birthmales

   Effect of enzyme imprinting of liver microsomal monooxygenases upon lifespan of rats

   Mechanisms of ageing and development·1 Jun 1999

5. Phenobarbital extends lifespan in rats (+17.5% mean lifespan).

   “A mean lifespan of experimental female rats increased by 17.5% compared to the level of control animals and did not change in male rats.”

   Animalsfemale rats3.5 mg/100 g body weight per dayduring 1-3 days after birthfemales

   Effect of enzyme imprinting of liver microsomal monooxygenases upon lifespan of rats

   Mechanisms of ageing and development·1 Jun 1999

6. Phenobarbital shortens lifespan in rats.

   “Nicotine and phenobarbital were found to diminish the mean survival times.”

   Animals

   Life-span investigations for carcinogenicity of some immune-stimulating, immunodepressive and neurotropic substances in Sprague-Dawley-rats

   Zeitschrift fur Krebsforschung und klinische Onkologie. Cancer research and clinical oncology·3 May 1976

1. Phenobarbital increases CYP2C6 in rats.

   “At 2 yr of age, in agreement with an overexpression of hepatic CYP2C6 and CYP2C7, both in vitro and in vivo drug metabolism was more rapid”

   Animalsliver

   Neonatal phenobarbital imprints overexpression of cytochromes P450 with associated increase in tumorigenesis and reduced life span

   FASEB journal : official publication of the Federation of American Societies for Experimental Biology·5 Jan 2005

More on CYP2C6

1. Phenobarbital increases urinary tract pathologies in rats (three- to fourfold).

   “three- to fourfold increase in urinary tract pathologies in male rats”

   Animalsfirst postpartum weekmales

   Neonatal phenobarbital imprints overexpression of cytochromes P450 with associated increase in tumorigenesis and reduced life span

   FASEB journal : official publication of the Federation of American Societies for Experimental Biology·5 Jan 2005

More on Urinary tract pathologies

1. Phenobarbital increases tumorigenesis in rats (two- to threefold).

   “associated two- to threefold increase in the incidence of tumors in barbiturate-exposed rats of both sexes”

   Animalsfirst postpartum week

   Neonatal phenobarbital imprints overexpression of cytochromes P450 with associated increase in tumorigenesis and reduced life span

   FASEB journal : official publication of the Federation of American Societies for Experimental Biology·5 Jan 2005

More on Tumorigenesis

1. Phenobarbital decreases sleeping time in rats (significantly lower).

   “In the phenobarbital treated female rats of different age the duration of sleeping time was significantly lower than that in control animals”

   Animalsfemale rats3.5 mg/100 g body weight per dayduring 1-3 days after birthfemales

   Effect of enzyme imprinting of liver microsomal monooxygenases upon lifespan of rats

   Mechanisms of ageing and development·1 Jun 1999

1. Phenobarbital increases cytochrome P-450s in rats (+34.5%).

   “The cytochrome P-450 content increased by 34.5% in phenobarbital treated female rats in the age of 12 months in comparison with control animals.”

   Animalsfemale ratsliver3.5 mg/100 g body weight per dayduring 1-3 days after birthfemales

   Effect of enzyme imprinting of liver microsomal monooxygenases upon lifespan of rats

   Mechanisms of ageing and development·1 Jun 1999

More on Cytochrome P-450s

1. Phenobarbital increases hepatocellular foci in rats.

   “Aged rat livers were thus more sensitive to the effects of PB than were livers of young rats.”

   Animalsin aged F344/NCr ratsin drinking waterlivermales

   Increased susceptibility of livers of aged F344/NCr rats to the effects of phenobarbital on the incidence, morphology, and histochemistry of hepatocellular foci and neoplasms

   Journal of the National Cancer Institute·1 Oct 1983

1. Phenobarbital increases mixed function oxidase activity in mice.

   “daily phenobarbitone injections for 4 days substantially increased enzyme activity in animals up to the middle of the age range tested.”

   Animalsup to the middle of the age range testeddaily injectionsliver4 daysmales

   Studies on age related changes in cytochrome P-450, cytochrome b-5 and mixed function oxidase activity in mouse liver microsomes, in relation to their phospholipid composition

   Archives of gerontology and geriatrics·1 May 1982

More on Mixed function oxidase activity

1. Phenobarbital lowers the risk of large granular lymphocyte leukemia in rats.

   “PB decreased the incidence of LGL leukemia but increased the incidence and multiplicity of hepatocellular GGT-positive foci, eosinophilic foci, and eosinophilic hepatocellular adenomas.”

   Animalsin aged F344/NCr ratsin drinking waterlivermales

   Increased susceptibility of livers of aged F344/NCr rats to the effects of phenobarbital on the incidence, morphology, and histochemistry of hepatocellular foci and neoplasms

   Journal of the National Cancer Institute·1 Oct 1983

More on Large granular lymphocyte leukemia

1. Phenobarbital raises the risk of hepatocellular adenoma in rats.

   “PB decreased the incidence of LGL leukemia but increased the incidence and multiplicity of hepatocellular GGT-positive foci, eosinophilic foci, and eosinophilic hepatocellular adenomas.”

   Animalsin aged F344/NCr ratsin drinking waterlivermales

   Increased susceptibility of livers of aged F344/NCr rats to the effects of phenobarbital on the incidence, morphology, and histochemistry of hepatocellular foci and neoplasms

   Journal of the National Cancer Institute·1 Oct 1983

More on Hepatocellular adenoma