A standardized extract of Ginkgo biloba suppresses doxorubicin‐induced oxidative stress and p53‐mediated mitochondrial apoptosis in rat testes

Abstract

Background and purpose: Doxorubicin evokes oxidative stress and precipitates cell apoptosis in testicular tissues. The aim of this study was to investigate whether the Ginkgo biloba extract 761 (EGb), a widely used herbal medicine with potent anti-oxidant and anti-apoptotic properties, could protect testes from such doxorubicin injury. Experimental approach: Sprague-Dawley male rats (8 weeks old) were given vehicle, doxorubicin alone (3 mg kg -1 every 2 days for three doses), EGb alone (5 mg kg -1 every 2 days for three doses), or EGb followed by doxorubicin (each dose administered 1 day after EGb). At 7 days after the first drug treatment oxidative and apoptotic testicular toxicity was evaluated by biochemical, histological and flow cytometric analyses. Key results: Compared with controls, testes from doxorubicin-treated rats displayed impaired spermatogenesis, depleted haploid germ cell subpopulations, increased lipid peroxidation products (malondialdehyde), depressed antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase and glutathione), reduced antioxidant enzyme expression (superoxide dismutase) and elevated apoptotic indexes (pro-apoptotic modulation of Bcl-2 family proteins, intensification of p53 and Apaf-1, release of mitochondrial cytochrome c, activation of caspase-3 and increase of terminal deoxynucleotidyl transferase nick-end labelling/sub-haploid cells), while EGb pretreatment effectively alleviated all of these doxorubicin-induced abnormalities in testes. Conclusions and implications:These results demonstrate that EGb protected against the oxidative and apoptotic actions of doxorubicin on testes. EGb may be a promising adjuvant therapy medicine, potentially ameliorating testicular toxicity of this anti-neoplastic agent in clinical practice.

Krüppel-like factor 6 regulates mitochondrial function in the kidney

“…KLF6 mediates apoptosis in the setting of ADR treatment. ADR has been previously shown to activate intrinsic apoptotic pathways in other models of tissue injury (18)(19)(20); we showed that a loss of KLF6 increased the susceptibility to ADR-induced mitochondrial injury. Therefore, we hypothesized that a loss of KLF6 would result in the activation of intrinsic apoptotic pathways with ADR treatment.…”

“…Nonetheless, we recognize that KLF6 may also regulate other genes involved in the activation of the intrinsic apoptotic pathway and mitochondrial injury. Although ADR has typically been observed to activate the intrinsic apoptotic pathway leading to tissue damage (19,20), the potential crosstalk between the extrinsic and intrinsic pathway in the setting of KLF6 depletion has to be further explored. Future studies will also need to determine the interaction between KLF6 and protein kinase, DNA-activated, catalytic peptide (PRKDC), a mice were treated with ADR at 12 weeks of age.…”

Aqueous extract of Huang-lian induces apoptosis in lung cancer cells via P53- mediated mitochondrial apoptosis

“…Two major pathways involved in the process have been investigated in great depth (Gustafsson and Gottlieb 2007). As p53 responds to both DNA damage and oxidative stress to trigger downstream apoptotic signalling, the mechanism for apoptosis seems to originate both from the pharmacological consequences of DNA injury and from oxidative stress (Yeh et al 2009;Zhou et al 2012). In this study, AHLE induced reduced expression of Bcl-2, Bcl-xl and greater expression of Bax.…”

Effect of Ginkgo biloba extract on sperm quality, serum testosterone concentration and histometric analysis of testes from adult Wistar rats

“…However, there were experimental studies which showed protective effects of GBE against testicular damage of many substances and other injuries: doxorubicin (Yeh et al, 2009), cadmium (Predes et al, 2011), cisplatin (Amin et al, 2012), diethylstilbestrol (Wang et al, 2008), carbon tetrachloride (Chávez-Moralez et al, 2010), testicular torsion/detorsion (Kanter, 2011). In addition, Taepongsorat et al (2008) showed that quercetin, one of the main components of GBE, ameliorated reproductive parameters such as motility, vitality and sperm concentration, and increased testicular weight in rats.…”