Phytol as an anticarcinogenic and antitumoral agent: An in vivo study in swiss mice with DMBA-Induced breast cancer.

Phytol (PHY) (3,7,11,15-tetramethylhexadec-2-en-1-ol) exhibits various pharmacological properties including toxicity and cytotoxicity, and exerts antitumor activity. Owing to the urgent need of new pharmaceutical formulations for breast cancer therapy, this study aimed at the evaluation of antitumor activity of PHY in 7,12-dimethylbenzanthracene-cancer-induced animal model. Comet assay was employed to evaluate the cytogenetics, DNA repair, and antigenotoxic activities of PHY in neoplastic (breast) and non-neoplastic rodent cells (bone marrow, lymphocytes, and liver). Additionally, hematological, biochemical, histopathological, and immunohistochemical analyses were carried out in experimental animals. Thirty nonpregnant female mice (n = 5) underwent 7 weeks treatment with 6 mg/kg pro-carcinogen, PHY (4 mg/kg), and cyclophosphamide (25 mg/kg). Induction of cancer was confirmed by histopathology and immunohistochemistry for Ki-67. Results suggest that PHY exhibits low toxicity in comparison with other groups in hematological, biochemical, histopathological, and organ size parameters. Additionally, PHY showed modulatory effects on the pro-carcinogen, and induced genotoxicity and apoptosis in breast cancer cells. Furthermore, it showed a DNA damage repair capacity in mouse lymphocytes. These data indicate that PHY may have the potential as an anticancer candidate in pharmaceutical consumption. © 2018 IUBMB Life, 71(1):200-212, 2019.

Mycotoxin-assisted mitochondrial dysfunction and cytotoxicity: Unexploited tools against proliferative disorders.

Mitochondria are the powerhouse of cells, which upon dysfunctions may lead to several diseases. Mycotoxins are the toxic secondary metabolites from fungi which are capable of causing diseases and death in humans and animals. They have a versatile mechanism of action in biological systems and can be used as lead compounds to treat some diseases including cancer. The present work encompasses analysis on the effects of mycotoxins on mitochondrial dysfunction. Electronic databases such as PubMed, ScienceDirect, Scopus, Web of Science, and Google Scholar were thoroughly searched for up-to-date published information associated with those mycotoxins and their effect on mitochondrial dysfunction. Findings suggest that mycotoxins such as citrinin, aflatoxin, and T-2 toxin exert multi-edged sword-like effects in test systems causing mitochondrial dysfunction. Mycotoxins can induce oxidative stress even at low concentration/dose that may be one of the major causes of mitochondrial dysfunction. On the other hand, activation of apoptotic caspases and other proteins by mycotoxins may lead to apoptotic cell death. Thus, mycotoxins-mediated mitochondrial dysfunction may be related to several chronic diseases which also makes these mycotoxins considerable as lead compounds for inducing toxic effects in cells. Their cytotoxic effects on cancer cells suggest their possible application as chemotherapeutic tools. © 2018 IUBMB Life, 70(11):1084-1092, 2018.

Toxicogenetic study of omeprazole and the modulatory effects of retinol palmitate and ascorbic acid on Allium cepa.

Omeprazole (OME) is a proton pump inhibitor used for the treatment of various gastric and intestinal disease; however, studies on its effects on the genetic materials are still restricted. The present study aimed to evaluate possible toxicogenic effects of OME in Allium cepa meristems with the application of cytogenetic biomarkers for DNA damage, mutagenic, toxic and cytotoxic effects. Additionally, retinol palmitate (RP) and ascorbic acid (AA) were also co-treated with OME to evaluate possible modulatory effects of OME-induced cytogenetic damages. OME was tested at 10, 20 and 40 µg/mL, while RP and AA at 55 µg/mL and 352.2 µg/mL, respectively. Copper sulphate (0.6 µg/mL) and dechlorinated water were used as positive control and negative control, respectively. The results suggest that OME induced genotoxicity and mutagenicity in A. cepa at all tested concentrations. It was noted that cotreatment of OME with the antioxidant vitamins RP and/or AA significantly (p < 0.05) inhibited and/or modulated all toxicogenic damages induced by OME. These observations demonstrate their antigenotoxic, antimutagenic, antitoxic and anticitotoxic effects in A. cepa. This study indicates that application of antioxidants may be useful tools to overcome OME-induced toxic effects.

A comprehensive review on biological properties of citrinin.

Citrinin (CIT) is a mycotoxin which causes contamination in the food and is associated with different toxic effects. A web search on CIT has been conducted covering the timespan since 1946. The accumulated data indicate that CIT is produced by several fungal strains belonging to Penicillium, Aspergillus and Monascus genera, and is usually found together with another nephrotoxic mycotoxin, ochratoxin A. Although, it is evident that CIT exposure can exert toxic effects on the heart, liver, kidney, as well as reproductive system, the mechanism of CIT-induced toxicity remains largely elusive. It is still controversial what are the genotoxic and mutagenic effects of CIT. Until now, its toxic effect has been linked to the CIT-mediated oxidative stress and mitochondrial dysfunction in biological systems. However, the toxicity strongly depends on its concentration, route, frequency and time of exposure, as well as from the used test systems. Besides the toxic effects, CIT is also reported to possess a broad spectrum of bioactivities, including antibacterial, antifungal, and potential anticancer and neuro-protective effects in vitro. This systematic review presents the current state of CIT research with emphasis on its bioactivity profile.

Cytogenotoxicological defense of retinyl palmitate in the front damage of antineoplastics.

Cancer, the multifactorial pathology and to date is the most lethal causes of death in the world. Cyclophosphamide (CPA) and doxorubicin (DOX) are the individually or combindly used two anticancer drugs. The antineoplastic drugs-mediated genetic instability can be overcome by using antioxidants. The study evaluated the cytogenotoxic modulatory potentials of retinyl palmitate (RP) caused by CPA and DOX in Swiss mice. For this, adult Mus musculus of either sex were divided equally regarding to the gender. Toxicogenetic effects were induced by the intraperitoneal (i.p.) administration of the CPA (20mg/kg) and/or DOX (2mg/kg), following to test for comet assay and micronucleus test in bone marrow cells after 48h (DOX) and 7h (CPA) of the administration of RP (100 IU/kg). Both CPA and DOX significantly (p<0.05) increased with the index and frequency of damages, clastogenic and/or aneugenic effects with the augmenting of micronuclei, demonstrating the cytotoxicity interference on the ratio of normochromatic to polychromatic erythrocytes and bone marrow cells of mice, that were found to reduce in RP treatment groups. In conclusion, RP has a modulatory effect on CPA and DOX-mediated cytogenotoxic events. The findings may be a good indication to manage the antioneoplastic drug-induced stress mediated detrimental effects by using RP, especially as a side effect minimizer.

In vivo antigenotoxic and anticlastogenic effects of fresh and processed cashew (Anacardium occidentale) apple juices.

Cashew apple juice and cajuina (processed juice) are drinks widely consumed in northeast Brazil. In vitro studies have shown that both juices have antimutagenic activity as well as antioxidant effects. These juices contain vitamins, carotenoids, and phenolic compounds. This in vivo study assessed the antigenotoxic and anticlastogenic effects of both drinks against genotoxicity and mutagenicity induced by cyclophosphamide. The comet, micronucleus, and chromosome aberrations tests were used. Male Swiss mice were divided into 6 groups (5 animals per group) and received the following by gavage, 0.15 mL/10 g body weight: group 1, water; group 2, cashew apple juice; group 3, cajuina juice; group 4, cashew apple juice and cyclophosphamide (50 mg/kg); group 5, cajuina juice and cyclophosphamide; group 6: cyclophosphamide. Both drinks significantly reduced DNA damage of peripheral blood cells (P<.001), with modulation percentages of 60.82% (cashew apple juice) and 82.19% (cajuina) when compared with the cyclophosphamide group. Cashew apple juice and cajuina modulated cyclophosphamide-induced micronucleus frequency, with up to 80.0% inhibition. Cashew apple juice and cajuina decreased the average number of cells with chromosome aberrations in bone marrow of mice by 53% and 65%, respectively. These findings demonstrate the high antigenotoxic and anticlastogenic potential of cashew apple juice and cajuina in vivo, which can be related to the antioxidant compounds found in both drinks.