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.

Ellagic acid attenuates bleomycin and cyclophosphamide-induced pulmonary toxicity in Wistar rats.

Use of bleomycin (BLM) and cyclophosphamide (CP) as chemotherapeutic drugs is associated with side effects including toxicity to respiratory system. Their co-administration may enhance lung toxicity which may subsequently progress to the lung fibrosis. Natural compounds have shown mitigating effects against toxicity of anticancer drugs. Ellagic acid (EA), a polyphenolic compound present in many fruits and nuts in addition to walnut has shown promising protective effect against toxicity of drugs and chemicals. We studied the ameliorative effect of EA on lung toxicity in rats exposed to CP (150 mg/kg b.w., i.p.) and BLM (10 U/kg b.w., i.t.). EA (15 mg/kg b.w., p.o.×14 days) treatment modulated enhanced hydroxyproline level, lipid peroxidation, myeloperoxidase activity, nitric oxide production and protein carbonyl formation in lungs of rats exposed to toxic anticancer drugs. There was a marked decrease in GSH content and activities of antioxidant enzymes as a result of BLM and CP treatment. Bronchoalveolar lavage fluid showed increased level of cytotoxicity markers in drug treated animals. Treatment with EA attenuated these changes. Histopathological findings also showed protective effects of EA. In conclusion, EA emerged as a natural protectant with an ability to protect lungs from onslaught of pulmonary toxicity of anticancer drugs.

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.

In vivo cytogenetic and oxidative stress-inducing effects of cypermethrin in freshwater fish, Channa punctata Bloch.

Synthetic pyrethroids are considered to be safe over other insecticides. Many of the newest pyrethroids lack ecotoxicity data. However, animal data indicate that their use may pose risk to environmental biota. The cytogenetic effects of cypermethrin, an α-class type II pyrethroid were evaluated using robust genotoxicity assay of chromosomal aberration (CA) and micronucleus (MN) tests in highly mitotic kidney cells and in erythrocytes of a freshwater fish, Channa punctata Bloch. In order to understand biochemical mechanism of genotoxic effects, oxidative stress parameters were also studied in fish erythrocytes. Fish exposed to cypermethrin (0.4, 0.8 and 1.2 µg/l for 48 and 72 h) showed increased frequencies of CA and MN in a concentration-dependent manner. Fish exposed to positive genotoxin, ethyl methane sulfonate (EMS) also showed significant increase in frequencies of CA and MN. The genotoxic effects were invariably accompanied and correlated with increased oxidative stress and disturbance of antioxidant enzymes.