Nordihydroguiaretic acid attenuates skin tumorigenesis in Swiss albino mice with the condition of topical co-administration of an immunosuppressant.

Drug and chemically-induced immunosuppression has been implicated as a confounding factor for cancer development. Management of cancer in such situation is often a challenging task. We tested the efficacy of nordihydroguiaretic acid (NDGA) against immunosuppressant tacrolimus-induced augmentation of mouse skin tumorigenesis. It was observed that topical administration of tacrolimus significantly accelerated the tumor promotion events in dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA) promoted two-stage mouse skin carcinogenesis, which were accompanied by reduced CD4(+)/CD8(+) ratio of lymph nodes and serum IL-2 level. NDGA pre-treatment before each TPA application reduced the tumor incidence, its multiplicity and volume together with improvement in histopathological alterations and decrease in proliferating cell nuclear antigen (PCNA) labeling index (LI). However, NDGA had no significant influence on the immunosuppressive effect of tacrolimus. The present study demonstrates chemopreventive effect of NDGA in normal as well as in the condition of immunosuppression. Thus, NDGA has the potential to inhibit or delay the onset of tumor development during immunosuppressive regimen.

Melatonin ameliorates bisphenol A-induced biochemical toxicity in testicular mitochondria of mouse.

Bisphenol A (BPA) is a monomer of polycarbonate plastic used to manufacture plastic baby bottles and lining of food cans. It has endocrine-disrupting potential and exerts both toxic and estrogenic effects on mammalian cells. We studied BPA-induced perturbation of mitochondrial marker enzymes in testes of Swiss albino mice and its amelioration by melatonin. Mice exposed to standardized dose of BPA (10 mg/kg body weight) orally for 14 days showed decrease in activities of marker mitochondrial enzymes such as succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, monoamine oxidase and NADH dehydrogenase. Besides, it also affected activities of antioxidant enzymes such as superoxide dismutase, glutathione reductase and glutathione peroxidase. BPA also caused lipid peroxidation (LPO) and decrease in reduced glutathione (GSH) content of mitochondria. Concomitant melatonin administration (10 mg/kg body weight; intraperitoneally for 14 days) lowered mitochondrial lipid peroxidation. It also restored the activity of mitochondrial marker enzymes and ameliorated decreased enzymatic and non-enzymatic antioxidants of mitochondria. These results demonstrate that melatonin has a potential role in ameliorating BPA-induced mitochondrial toxicity and the protection is due to its antioxidant property or by the direct free radical scavenging activity.

Iron deficiency augments bisphenol A-induced oxidative stress in rats.

Bisphenol A (BPA), an estrogenic environmental contaminant is also known for oxidative stress-inducing effect. Malnutrition is recognized as a confounding factor in oxidative stress. However, little is known about effect of malnutrition on oxidative stress induced by BPA or other endocrine disrupting chemicals (EDCs). We studied effect of malnutrition (iron deficiency) in rats chronically exposed to low levels of BPA taking into consideration the oxidative stress and antioxidant status in liver, kidney and gonads. Iron deficiency significantly elevated level of lipid peroxidation in BPA-exposed rats. Similarly, decrease in reduced glutathione level was more significant in rats maintained on iron deficient diet compared to those maintained on normal diet. Iron deficiency also significantly modulated activities of vital antioxidant enzymes in all the tissues. Female rats showed more vulnerability than males to iron-deficiency modulated effects of BPA on the above parameters. This study demonstrated that malnutrition, especially iron deficiency, might act as a confounding factor in EDC-induced oxidative stress. However, more studies may be needed to confirm effect of nutritional factors on estrogenic activity of BPA or other EDCs.