Inhibitory effects of phenolic compounds on development of naturally occurring preneoplastic hepatocytic foci in long-term feeding studies using male F344 rats

Kalonia

Journal of Asian Natural Products Research

2009

Sesamol (SML) obtained from sesame seeds (Sesamum indicum, Linn, Pedaliaceae) has been used as a traditional health food in India and other countries since a long time. Besides its good antioxidant activity, SML is currently receiving considerable attention in relation to neurological disorders. Therefore, the present study has been designed to explore the protective role of SML in 3-nitropropionic acid (3-NP)-induced neurotoxicity in animals. Male rats were given 3-NP (10 mg/kg) treatment for 14 days. Various behavioral observations (body weight, locomotor activity), oxidative damage (lipid peroxidation, nitrite level, superoxide dismutase, and catalase enzyme), and mitochondrial enzyme complex functions were also assessed in the striatum, cortex, and hippocampal regions of the brain. 3-NP treatment significantly impaired locomotor activity, motor coordination, body weight, oxidative damage, and mitochondrial enzyme complex functions as compared with vehicle-treated groups. SML (5, 10, and 20 mg/kg) pre-treatment significantly improved body weight, locomotor activity, motor coordination, and attenuated oxidative damage in different regions of rat brain. Besides these, SML treatment also significantly improved mitochondrial enzymes in all regions of the brain as compared with the respective control (3-NP) group. The present study suggests that SML could be used as effective agents in the management of Huntington's disease.

Section: Discussionsupporting

confidence: 90%

Sesamol attenuate 3-nitropropionic acid-induced Huntington-like behavioral, biochemical, and cellular alterations in rats

Kalonia

Journal of Asian Natural Products Research

2009

Critical Reviews in Toxicology

“…248 Other data indicate that HQ does not selectively damage GSTpositive hepatocytes. 249 Finally, a recent study 250 examining hepatic tissue from a previous HQ carcinogenicity bioassay 220 indicated that prolonged (2-year) dietary exposure of F344 rats to 2% HQ resulted in decreased numbers and area of GST-positive hepatic foci. These findings generally support the conclusion that HQ lacks significant hepatocarcinogenic activity in rodents.…”

Section: Other Data Related To Carcinogenesismentioning

confidence: 99%

The Toxicology of Hydroquinone — Relevance to Occupational and Environmental Exposure

DeCaprio¹

1999

175

128

Hydroquinone (HQ) is a high-volume commodity chemical used as a reducing agent, antioxidant, polymerization inhibitor, and chemical intermediate. It is also used in over-the-counter (OTC) drugs as an ingredient in skin lighteners and is a natural ingredient in many plant-derived products, including vegetables, fruits, grains, coffee, tea, beer, and wine. While there are few reports of adverse health effects associated with the production and use of HQ, a great deal of research has been conducted with HQ because it is a metabolite of benzene. Physicochemical differences between HQ and benzene play a significant role in altering the pharmacokinetics of directly administered when compared with benzene-derived HQ. HQ is only weakly positive in in vivo chromosomal assays when expected human exposure routes are used. Chromosomal effects are increased significantly when parenteral or in vitro assays are used. In cancer bioassays, HQ has reproducibly produced renal adenomas in male F344 rats. The mechanism of tumorigenesis is unclear but probably involves a species-, strain-, and sex-specific interaction between renal tubule toxicity and an interaction with the chronic progressive nephropathy that is characteristic of aged male rats. Mouse liver tumors (adenomas) and mononuclear cell leukemia (female F344 rat) have also been reported following HQ exposure, but their significance is uncertain. Various tumor initiation/promotion assays with HQ have shown generally negative results. Epidemiological studies with HQ have demonstrated lower death rates and reduced cancer rates in production workers when compared with both general and employed referent populations. Parenteral administration of HQ is associated with changes in several hematopoietic and immunologic endpoints. This toxicity is more severe when combined with parenteral administration of phenol. It is likely that oxidation of HQ within the bone marrow compartment to the semiquinone or p-benzoquinone (BQ), followed by covalent macromolecular binding, is critical to these effects. Bone marrow and hematologic effects are generally not characteristic of HQ exposures in animal studies employing routes of exposure other than parenteral. Myelotoxicity is also not associated with human exposure to HQ. These differences are likely due to significant route-dependent toxicokinetic factors. Fetotoxicity (growth retardation) accompanies repeated administration of HQ at maternally toxic dose levels in animal studies. HQ exposure has not been associated with other reproductive and developmental effects using current USEPA test guidelines. The skin pigment lightening properties of HQ appear to be due to inhibition of melanocyte tyrosinase. Adverse effects associated with OTC use of HQ in FDA-regulated products have been limited to a small number of cases of exogenous ochronosis, although higher incidences of this syndrome have been reported with inappropriate use of unregulated OTC products containing higher HQ concentrations. The most serious human health effect related to HQ is p...

J of Cosmetic Dermatology

“…HQ which is the simplest of the monocyclic phenols has similar properties to these antimutagenic and anticarcinogenic phenolics when fed to rats. For example, unlike kojic acid, another substance used to lighten skin, HQ has an inhibitory effect (29% reduction) in naturally occurring preneoplastic hepatic foci in F‐344/DuCrj rats when fed at 0.8% for 2 years 48,49 . HQ is also reported to reduce the number of preneoplastic lesions and DNA adducts induced by 2‐acetylaminofluorene, a potent hepatic carcinogen (personal communication, G.M.…”

Section: Hq Bioassay Results Are In Sharp Contrast To the Results Of mentioning

confidence: 99%

Hydroquinone and its analogues in dermatology – a risk‐benefit viewpoint

O’Donoghue

2006

Hydroquinone (HQ) has been used since the 1950s in commercially available over-the-counter skin lightener products and since the 1960s as a commercially available medical product. It is also used in cosmetic products such as hair dyes and products for coating finger nails. Beginning in 2001, HQ is no longer authorized for use in cosmetic skin lightening formulations in European Union countries, although products containing arbutin, an analogue of HQ, and botanicals, including plants that naturally contain HQ and arbutin, continue to remain available in European countries. The potential toxicity of HQ is dependent on the route of exposure, and toxicity in rodents is highly sex-, species-, and strain-specific. Subchronic and chronic toxicity in experimental animals is primarily limited to nephrotoxicity in male F-344 rats. Dermal toxicity studies, even those conducted in the sensitive male F-344 rat, are essentially devoid of systemic toxicity. Developmental and reproductive toxicity studies with HQ in rats and rabbits have not demonstrated significant effects. Cancer bioassay data for HQ demonstrate limited effects and are not sufficient to classify HQ for human carcinogenicity. Epidemiology and occupational studies of workers with extensive exposure to HQ have not reported any evidence of adverse systemic health effects or carcinogenicity. A risk-benefit approach is recommended for assessing the available data for HQ, arbutin, and other materials in use as, or proposed for use as, skin lighteners to provide optimal therapeutic benefits to patients with pigmentary changes of the skin.