RESUMEN
Being a common environmental pollutant, cadmium causes detrimental health effects, including testicular injury. Herein, we document the ameliorative potential of quercetin, a potent antioxidant, against cadmium-induced geno-cytotoxicity and steroidogenic toxicity in goat testicular tissue. Cadmium induced different comet types (Type 0 - Type 4), indicating the varying degree of DNA-damage in testicular cells. The quantitative analysis at 50 and 100 µM cadmium concentration revealed the DNA damage with per cent tail DNA as 75.78 ± 1.49 and 94.65 ± 0.95, respectively, in comparison to the control group (8.87 ± 0.48) post 8 h exposure duration. Cadmium caused a substantial decrease in the activity of key steroidogenic enzymes' (3ß-HSD and 17ß-HSD) along with reduction of testosterone level in testicular tissue. Furthermore, cadmium treatment induced various types of deformities in sperm, altered the Bax/Bcl-2 expression ratio in testicular tissue and thus suggesting the apoptosis-mediated death of testicular cells. Simultaneous quercetin supplementation, however, significantly (p < 0.05) averted the aforementioned cadmium-mediated damage in testicular tissue. Conclusively, the cadmium-induced DNA-damage and decrease in steroidogenic potential results in death of testicular cells via apoptosis, which was significantly counteracted by quercetin co-supplementation, and thus preventing the cadmium-mediated cytotoxicity of testicular cells.
Asunto(s)
Apoptosis , Cadmio , Daño del ADN , Cabras , Quercetina , Testículo , Animales , Masculino , Quercetina/farmacología , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , Apoptosis/efectos de los fármacos , Cadmio/toxicidad , Daño del ADN/efectos de los fármacos , Antioxidantes/farmacologíaRESUMEN
In search of selective carbonic anhydrase (CA) IX inhibitors endowed with apoptotic inducing properties, we designed and synthesised two subsets of 4- and 3-(5-aryl-(4-phenylsulphonyl)-1H-1,2,3-triazol-1-yl)benzenesulphonamides. All compounds were assayed for human carbonic anhydrase (hCA) isoforms I, II, IV, and IX inhibition. Isoforms hCA I and hCA IV were weakly inhibited by most of the synthesised compounds. Many four-substituted benzenesulphonamides displayed low nanomolar inhibition against isoform hCA II, unlike the three-substituted analogues. All target compounds exhibited good inhibition profile with KI values ranging from 16.4 to 66.0 nM against tumour-associated isoform hCA IX. Some selective and potent inhibitors of hCA IX were assayed for in vitro apoptotic induction in goat testicular cells. Compounds 10d and 10h showed interesting apoptotic induction potential. The present study may provide insights into a strategy for the design of novel anticancer agents based on hCA inhibitors endowed with apoptotic interference.
Asunto(s)
Sulfonamidas , Triazoles , Antígenos de Neoplasias , Apoptosis , Anhidrasa Carbónica I/metabolismo , Anhidrasa Carbónica IX/metabolismo , Inhibidores de Anhidrasa Carbónica/farmacología , Estructura Molecular , Relación Estructura-Actividad , Sulfonamidas/farmacología , Triazoles/farmacologíaRESUMEN
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 present era's demand for continuous pesticides' use to increase the agriculture outcome, has caused numerous health effects among which mammalian infertility, owing to reproductive toxicity, is serious. Thus, the present study emphasizes upon glyphosate (GLY) induced toxicity and mitigating effects of N-acetyl cysteine (NAC) in testicular cells of caprine by using various cytotoxic and biochemical parameters. GLY was found to induce several apoptotic attributes such as pyknotic nuclei, tubular degeneration, increased vacuolization, and so on, in testicular cells. GLY also decreased the cell viability and increased the incidence of apoptosis in testicular cells in a dose- and time-dependent manner as revealed by MTT assay and Fluorescence (ethidium bromide/acridine orange) assay, respectively. It also increased the level of oxidative stress as evident with an increase in lipid peroxidation and decline in antioxidant power along with the decreased enzymatic activity of different antioxidant enzymes (SOD, CAT, and GST). However, NAC supplementation showed antagonistic results in GLY-treated testicular tissues with maximum amelioration at the highest dose, thereby decreasing GLY-mediated apoptosis rate and oxidative stress. Maximum amelioration was reported at 10 mM NAC concentration. Reduced GLY toxicity due to NAC will prove NAC to be an excellent approach for dealing with male reproductive toxicity at the cellular level, benefiting the mammalian reproductive status.
Asunto(s)
Acetilcisteína , Infertilidad , Acetilcisteína/farmacología , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Apoptosis , Células Germinativas/metabolismo , Glicina/análogos & derivados , Cabras/metabolismo , Infertilidad/metabolismo , Masculino , Estrés Oxidativo , Testículo/metabolismo , GlifosatoRESUMEN
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).
Asunto(s)
Acetilcisteína , Cabras , Acetilcisteína/farmacología , Animales , Apoptosis , Electrones , Células Germinativas , Glicina/análogos & derivados , Masculino , Microscopía Electrónica de Transmisión , Estrés Oxidativo , GlifosatoRESUMEN
Cadmium (Cd), an environmental toxic heavy metal, has been reported to cause testicular toxicity, which contributes to the recent decline in male fertility worldwide. Quercetin (Qcn), a major dietary antioxidant, has been shown to have protective effects under various pathological conditions. However, whether Qcn provides protection against Cd-stimulated testicular toxicity remains obscured. The present study was therefore aimed at investigating the ameliorative effect of Qcn supplementation on Cd-induced toxicity in the goat testis in vitro in a dose-(10, 50, and 100 µM) and time-dependent (4 and 8 h) manner. Different cytotoxicity, genotoxicity, and biochemical analyses have been carried out using appropriate methods. Cytotoxicity in testicular cells induced by Cd treatment was apparently mitigated by Qcn treatment, evidenced by decreased apoptotic attributes or frequency in Qcn plus Cd-treated groups compared to the only Cd-treated groups. Qcn treatment provides substantial protection to the Cd-triggered aggression in oxidative (increased MDA levels) and total antioxidant capacity (reduced FRAP activity) in testicular tissue, indicating the anti-oxidative function of Qcn against Cd exposure. Moreover, Cd-induced decline in antioxidant status (CAT, SOD, and GST activity) was markedly restored by Qcn supplementation in testicular tissue. In conclusion, this study shows that Qcn treatment significantly attenuated the Cd-evoked testicular damage, suggesting its beneficial potential in preventing or at least in managing the gonadotoxicity in males induced by steadily increasing Cd contamination in the environment.
Asunto(s)
Antioxidantes/farmacología , Apoptosis , Cadmio/toxicidad , Estrés Oxidativo , Quercetina/farmacología , Espermatogénesis , Testículo/efectos de los fármacos , Animales , Cabras , Masculino , Oxidación-Reducción , Testículo/patologíaRESUMEN
The prevalence of female infertility cases has been increasing at a frightening rate, affecting approximately 48 million women across the world. However, oxidative stress has been recognized as one of the main mediators of female infertility by causing various reproductive pathologies in females such as endometriosis, PCOS, preeclampsia, spontaneous abortion, and unexplained infertility. Nowadays, concerned women prefer dietary supplements with antioxidant properties over synthetic drugs as a natural way to lessen the oxidative stress and enhance their fertility. Therefore, the current review is an attempt to explore the efficacy of various natural antioxidant compounds including vitamins, carotenoids, and plant polyphenols and also of some medicinal plants in improving the fertility status of females. Our summarization of recent findings in the current article would pave the way toward the development of new possible antioxidant therapy to treat infertility in females. Natural antioxidant compounds found in fruits, vegetables, and other dietary sources, alone or in combination with other antioxidants, were found to be effective in ameliorating the oxidative stress-mediated infertility problems in both natural and assisted reproductive settings. Numerous medicinal plants showed promising results in averting the various reproductive disorders associated with female infertility, suggesting a plant-based herbal medicine to treat infertility. Although optimum levels of natural antioxidants have shown favorable results, however, their excessive intake may have adverse health impacts. Therefore, larger well-designed, dose-response studies in humans are further warranted to incorporate natural antioxidant compounds into the clinical management of female infertility.
Asunto(s)
Antioxidantes/administración & dosificación , Suplementos Dietéticos , Infertilidad Femenina/metabolismo , Infertilidad Femenina/prevención & control , Animales , Femenino , Fertilidad/efectos de los fármacos , Humanos , Estrés Oxidativo/efectos de los fármacos , Polifenoles/administración & dosificaciónRESUMEN
Cadmium (Cd) is a toxic heavy metal with no known biological functions in the human body. Due to a considerably long biological half-life and very low rate of excretion, accumulation of Cd in different body organs (eg, liver, kidney, and testes) over time is associated with perturbed functioning of these organs. Recent studies have shown the extreme sensitivity of the testes to Cd toxicity. In testes, Cd has been reported to induce oxidative stress, apoptosis of spermatogenic cells, reduction in androgen production and sperm functions. Moreover, Cd in combination with other environmental toxicants may be responsible for the declining fertility of males in both animals and humans. Pinpointing how Cd toxicity affects various testicular processes will be imperative for the development of preventative measures to promote fertility among males. Therefore, in the present review, we summarize the recent findings related to the Cd-induced oxidative toxicity, apoptotic toxicity, steroidogenic toxicity, and spermatotoxicity, along with their possible mechanisms in testicular tissue of different animal species. In addition, the utilization of various antioxidant compounds, medicinal plants and other compounds for the management of Cd toxicity in testes is discussed.