RESUMEN
Cancer is a deadly disease that affects a cell's metabolism and surrounding tissues. Understanding the fundamental mechanisms of metabolic alterations in cancer cells would assist in developing cancer treatment targets and approaches. From this perspective, metabolomics is a great analytical tool to clarify the mechanisms of cancer therapy as well as a useful tool to investigate cancer from a distinct viewpoint. It is a powerful emerging technology that detects up to thousands of molecules in tissues and biofluids. Like other "-omics" technologies, metabolomics involves the comprehensive investigation of micromolecule metabolites and can reveal important details about the cancer state that is otherwise not apparent. Recent developments in metabolomics technologies have made it possible to investigate cancer metabolism in greater depth and comprehend how cancer cells utilize metabolic pathways to make the amino acids, nucleotides, and lipids required for tumorigenesis. These new technologies have made it possible to learn more about cancer metabolism. Here, we review the cellular and systemic effects of cancer and cancer treatments on metabolism. The current study provides an overview of metabolomics, emphasizing the current technologies and their use in clinical and translational research settings.
Asunto(s)
Metabolómica , Neoplasias , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Metabolómica/métodos , Redes y Vías Metabólicas , AnimalesRESUMEN
Cadmium (Cd) is a ubiquitous heavy metal toxicant with no biological function in the human body. Considerably, because of its long biological half-life and very low excretion rate, Cd is inclined to accumulate and cause deleterious effects on various body organs (e.g., liver, kidney, and ovary) in humans and animals. Ovaries are the most vulnerable targets of Cd toxicity. Cd has been shown to induce oxidative stress, follicular atresia, hormonal imbalance, and impairment of oocyte growth and development. Moreover, Cd toxicity has been associated with increasing incidences of menstrual disorders, pregnancy loss, preterm births, delayed puberty, and female infertility. Therefore, it is crucial to understand how Cd poisoning impacts specific ovarian processes for the development of preventive interventions to enhance female fertility. The current review attempts to collate the recent findings on Cd-induced oxidative stress, follicular apoptosis, steroid synthesis inhibition, and teratogenic toxicity, along with their possible mechanisms in the ovarian tissue of different animal species. Additionally, the review also summarizes the studies related to the use of many antioxidants, medicinal herbs, and other compounds as remedial approaches for managing Cd-induced ovarian toxicity.
Asunto(s)
Intoxicación por Cadmio , Cadmio , Embarazo , Animales , Recién Nacido , Femenino , Humanos , Cadmio/toxicidad , Cadmio/metabolismo , Ovario , Atresia Folicular , Estrés Oxidativo , Antioxidantes/metabolismo , Sustancias PeligrosasRESUMEN
Increase in success of cancer treatment with advancement in the screening, prognosis and diagnosis protocols have significantly improved the rate of cancer survivorship. With the declining cancer mortality, however, the cancer survivors are also subjected to the adverse consequences of chemotherapy, particularly in the female reproductive system. Recent studies have shown the sensitivity of the ovarian tissue to the chemotherapeutic drugs-induced toxicity. Several in vitro and in vivo studies have assessed the toxic effects of chemotherapeutic drugs. The most frequently used chemotherapeutic drugs such as doxorubicin, cyclophosphamide, cisplatin and paclitaxel have been reported to cause ovarian damage, diminution of follicular pool reserve, premature ovarian failure and early menopause, resulting into declining fertility potential among females. The chemotherapy often employs combination of drug regimen to increase the efficacy of the treatment. However, the literature mostly consists of clinical data regarding the gonadotoxicity caused by anticancer drugs but there lacks the understanding of toxicity mechanism. Therefore, understanding of the different toxicity mechanisms will be helpful in development of possible therapeutic interventions for preservation of declining female fertility among cancer survivors. The current review comprehends the underlying mechanisms of female reproductive toxicity induced by the most commonly used chemotherapeutic drugs. In addition, the review also summarizes the recent findings related to the use of various protectants to diminish or at least in managing the toxicity induced by different chemotherapeutic drugs in females.
Asunto(s)
Antineoplásicos , Folículo Ovárico , Femenino , Humanos , Antineoplásicos/farmacología , Cisplatino/farmacología , Ciclofosfamida/efectos adversos , OvarioRESUMEN
Increasing evidence has demonstrated that cadmium (Cd), a common environmental toxicant, has been associated with testicular toxicity. Quercetin, an efficient flavonoid, has been shown to exert cytoprotective effect in numerous pathological processes. The current study has employed ultrastructural analysis to examine the Cd-induced toxicity in goat testicular tissue along with the ameliorative action of quercetin in a dose- and time-dependent manner in-vitro. Results of transmission electron microscopy (TEM) revealed that at lower selected concentrations (10 and 50 µM), Cd induced apoptosis-mediated cytotoxicity in testicular tissue as supported by presence of various morphological attributes of apoptosis in testicular germ cells such as condensed and marginated chromatin followed by breakdown of chromatin material, swollen mitochondria, and vacuolization. At 100 µM concentration, along with apoptosis, Cd-induced cytotoxicity in testicular tissue was associated with induction of necrosis also. However, the simultaneous supplementation of antioxidant quercetin has markedly abrogated the testicular cytotoxicity as shown by restoration of Cd-evoked aberrant ultrastructure of testicular germ cells in a dose- and time-dependent manner, providing a basis for future studies to involve quercetin in management of Cd-induced reproductive toxicity in males.
Asunto(s)
Antioxidantes , Quercetina , Animales , Antioxidantes/farmacología , Apoptosis , Cadmio/toxicidad , Cromatina/metabolismo , Células Germinativas/metabolismo , Cabras/metabolismo , Masculino , Estrés Oxidativo , Quercetina/farmacología , TestículoRESUMEN
The agricultural pesticide poisoning is currently the most thrust area of human health concern. Pesticide-induced cytotoxicity and the corresponding reproductive toxicity in today's scenario is not a concealed reality that has to be considered for the continuation of respective race. Here, the transmission electron microscopy (TEM) technique was employed to investigate the adverse impact of glyphosate (GLY) and its mitigation by N-acetyl-L-cysteine (NAC) in goat testicular germ cells under in vitro conditions. The ultrastructural observations of testicular tissue from GLY-treated groups at different concentrations (0.1 and 4 mg/ml) and exposure durations (8 and 12 h) revealed that this organophosphate herbicide induced different apoptotic characteristics in testicular germ cells in a time- and dose-dependent manner. However, NAC (10 mM), being a potent antioxidant, was found to mitigate GLY-induced cytotoxicity in testicular cells as evidenced by fewer apoptotic characteristics in GLY plus NAC-treated groups, suggesting its beneficial potential in alleviating the GLY-induced gonadotoxicity in males.Abbreviations: GLY (Glyphosate), NAC (N-acetyl-L-cysteine), TEM (Transmission electron microscopic), GE (genetic engineered), Organophosphate (OPs).