Effect of chemotherapy exposure prior to pregnancy on fetal brain tissue and the potential protective role of quercetin

Abstract

Cyclophosphamide (CYC) and doxorubicin (DOX) are among the most effective and widely used anticancer chemotherapeutic drugs. Potential chemopreventive and chemotherapeutic functions have recently been attributed to flavonoids. We hypothesized that Quercetin (QR) would protect against the toxic effects of chemotherapeutic agents applied prior to pregnancy. Rats were treated with the chemotherapeutic drugs CYC (27 mg/kg) and DOX (1.8 mg/kg) applied in a single intraperitoneal dose once every 3 weeks for 10 weeks. QR was administered at a dose of 10 mg/kg/day by oral gavage. 48 h following the experimental chemotherapy exposure, female rats were transferred to cages containing male rat for mating. Fetal brain tissues were removed from fetuses extracted by cesarean section on the 20th day of gestation for evaluation of antioxidant parameters. A significant increase in superoxide dismutase and malondialdehyde activity was observed in CYC and DOX treatment groups relative to the control group (p \ 0.05). Similarly, carnitine acylcarnitine translocase and Glutathione activity was significantly reduced in the CYC and DOX groups relative to the control group (p \ 0.05). Our results indicate that the use of chemotherapeutic drugs before pregnancy can result in oxidative damage to fetal brain tissue. Therefore, women who have been exposed to chemotherapy and may become pregnant should be treated with antioxidant compounds such as QR to reduce the risk of damage to fetal brain tissues.

Protective effects of quercetin against brain injury in a rat model of lipopolysaccharide‐induced fetal brain injury

“…In vitro and brain injury animal model studies have consistently revealed that QR exerts neuroprotective function through antagonizing oxidative stress. In the fetal brain, QR is able to suppress maternal chemotherapy induced oxidative stress (Dogan et al, 2015). Consistent with this observation, our results showed that QR potently suppressed oxidative stress induced by LPS exposure in fetal brain.…”

“…QR (10 mg/kg/day, Alfa Aesar GmbH, Karlsruhe, Germany) was administered via oral gavage following LPS or saline injection. Dose of QR was determined according to a previous study (Dogan et al, 2015). Control rats were ip injected with 0.1 mL sterile saline.…”

“…The levels of oxidative stress in fetal brain were determined by the activities of catalase (CAT) and superoxide dismutase (SOD) and the concentrations of glutathione (GSH) and malondialdehyde (MDA) as described previously (Dogan et al, 2015). Briefly, MDA was measured according to its reaction with thiobarbituric acid.…”

“…In vivo studies have also shown that QR suppresses neuroinflammation and is beneficial in the treatment of neural disorders (Wang et al, 2018; Yang et al, 2018). Additionally, QR alleviates oxidative damage caused by chemotherapeutic drugs introduced to female rats before pregnancy (Dogan et al, 2015). However, it is not clear whether QR has any protective effect against maternal infection induced birth defects, especially brain injury.…”

Telomerase Inhibitors from Natural Products and Their Anticancer Potential

“…With respect to the research on the impact of quercetin on apoptosis, Kou [ 173 ] and Gibellini et al [ 174 ] found that quercetin in a dose-dependent manner induces apoptosis, arrest the cells at different cycles and block their growth in various cancer cells. In addition, several animal studies have also been conducted and they found the mechanisms of chemopreventive and therapeutic effects of quercetin [ 175 , 176 , 177 , 178 ]. The epidemiological studies also reported that the regular consumption of quercetin (1.01–31.7 mg/day) could reduce the ovarian cancer risk [ 179 ].…”