Protective Effect of Ascorbic Acid on Hepatotoxicity Caused by Sodium Nitrite Plus Aminopyrine

Kamm, Jerome J.; Dashman, Theodore; Conney, Allan H.; Burns, J. J.

doi:10.1073/pnas.70.3.747

Cited by 61 publications

(12 citation statements)

References 9 publications

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“…When significant differences by ANOVA were detected analysis of a difference between the means of the treated and control groups were performed by using Dunnett's test. The percent protection was calculated according to the equation described by Kamm et al, 1973: 100-100 (D 1/ D 2 ) Where D 1 is the mean for the protected group-the mean for the controls and D 2 is the mean for the hepatotoxic group-the mean for the controls.…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective effects of Hibiscus, Rosmarinus and Salvia on azathioprine-induced toxicity in rats

2005

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Section: Discussionmentioning

confidence: 99%

Hepatoprotective effects of Hibiscus, Rosmarinus and Salvia on azathioprine-induced toxicity in rats

2005

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“…On the other hand, when AsA was given with NaNO 2 and AP, the inhibitory effect was less potent than that of HTHQ. It was reported that AsA and sodium ascorbate (NaAsA) protected rats against liver tumor production or hepatotoxicity by simultaneous treatment with NaNO 2 and secondary amines such as AP 3,22) or morpholine. 23) AsA has been shown to inhibit the genotoxicity of nitrosoamines derived from NaNO 2 and secondary amines such as morpholine or proline in the Comet assay, 24) and is suggested to inhibit nitrosamine formation by reducing nitrous anhydride to nitric oxide, a non-nitrosating species, in the absence of catalysts.…”

Section: Discussionmentioning

confidence: 99%

Effects of Antioxidant 1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi‐organ Carcinogenesis Model

Yada

Hirose

Tamano³

et al. 2002

Japanese Journal of Cancer Research

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The effect of antioxidant, 0.25% 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ) or 0.25% ascorbic acid (AsA), on carcinogenesis induced by administration of 0.05% aminopyrine (AP) and 0.05% sodium nitrite (NaNO 2 ), was examined using a rat multi-organ carcinogenesis model. Groups of twenty F344 male rats were treated sequentially with an initiation regimen of Ndiethylnitrosamine, N-methyl-N-nitrosourea, N-butyl-N-(4-hydroxybutyl)nitrosamine, N,N′ ′ ′ ′-dimethylhydrazine and 2,2′ ′ ′ ′-dihydroxy-di-n-propylnitrosamine during the first 4 weeks, followed by AP + + + +NaNO 2 , AP + + + +NaNO 2 + + + +HTHQ, AP + + + +NaNO 2 + + + +AsA, NaNO 2 + + + +HTHQ, NaNO 2 + + + +AsA, each of the individual chemicals alone or basal diet and tap water as a control. All surviving animals were killed at week 28, and major organs were examined histopathologically for development of preneoplastic and neoplastic lesions. In the AP + + + +NaNO 2 group, the incidences of hepatocelluar adenomas and hemangiosarcomas were 95% and 35%, respectively. When HTHQ or AsA was simultaneously administered, the incidences decreased to 58% and 11%, or to 80% and 15%, respectively. On the other hand, in the AP + + + +NaNO 2 group and the NaNO 2 -alone group, when HTHQ, but not AsA, was simultaneously administered, the incidence of carcinomas in the forestomach significantly increased. The results suggest that HTHQ can prevent tumor production induced by AP and NaNO 2 more effectively than AsA. On the other hand, an enhancing or possible carcinogenic effect of simultaneous administration of HTHQ and NaNO 2 only on the forestomach is suggested, while simultaneous treatment with the same dose of AsA and NaNO 2 may not be carcinogenic to the forestomach or other organs.Key words: Antioxidants -Aminopyrine -Sodium nitrite -Carcinogenesis -RatMany nitrosoamines are known to induce tumors in various organs.1) It was reported that some drugs with secondary or tertiary amino groups reacted with nitrite under acidic conditions to form nitrosamines in vitro and in vivo. [2][3][4][5] In particular, aminopyrine (AP) is known to react with sodium nitrite (NaNO 2 ) to form dimethylnitrosamine (DMN), which is a potent liver, lung and renal carcinogen.2, 3, 6) Feeding of AP and NaNO 2 to rats has been shown to cause acute liver damage due to formation of DMN and eventually to cause liver tumors upon chronic treatment. 2,7,8) It is also known that ascorbic acid (AsA), and phenolic antioxidants such as caffeic acid, ferulic acid, butylated hydroxyanisole (BHA) and propyl gallate, inhibit the formation of DMN in rats receiving AP and NaNO 2 . 4,5) An inhibitory effect of caffeic acid on the endogenous formation of N-nitrosoproline was demonstrated in man. 9)Kuenzig et al. suggest that dietary phenols may play an important role in the prevention of carcinogenesis by inhibiting the formation of nitrosamines. 5)On the other hand, it has been reported that mutagenic compounds were formed by the interaction of polyphenols with nitrite in vitro.10, 11) It was also reported tha...

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“…Even the latter possibility is sometimes worth considering. For example, it has been suggested that vitamin C may prevent the formation of carcinogenic nitrosamines by reacting with nitrite within the stomach (12,13).…”

Section: Vitamin C -General Observationsmentioning

confidence: 99%

A re-evaluation of nutritional goals -not just deficiency counts

Hemilä¹

1986

Medical Hypotheses

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There is considerable controversy about the soundness and relevance of so-called "megavitamin" therapy for various illnesses. In this article it is suggested that this disagreement is caused to a large extent by the use of two very different approaches to nutrition, which are referred to here as the "nutritional need" and "optimal intake" approaches. It is clear that a re-evaluation of the goals of nutrition is required, as nutritional recommendations deal mainly with the prevention of deficiency diseases and are not concerned with optimal levels of intake.

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Protective Effect of Ascorbic Acid on Hepatotoxicity Caused by Sodium Nitrite Plus Aminopyrine

Cited by 61 publications

References 9 publications

Hepatoprotective effects of Hibiscus, Rosmarinus and Salvia on azathioprine-induced toxicity in rats

Hepatoprotective effects of Hibiscus, Rosmarinus and Salvia on azathioprine-induced toxicity in rats

Effects of Antioxidant 1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi‐organ Carcinogenesis Model

A re-evaluation of nutritional goals -not just deficiency counts

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