Resveratrol protects against cisplatin-induced ovarian and uterine toxicity in female rats by attenuating oxidative stress, inflammation and apoptosis.

Cisplatin is an important antineoplastic drug used in multiple chemotherapeutic regimens but unfortunately causes serious toxic effects as ovarian and uterine toxicity. This study aimed to investigate the potential protective effect of resveratrol (RSV) against cisplatin-induced ovarian and uterine toxicity in female rats. Thirty-two female Wistar rats were divided randomly into four groups (n = 8 in each). Control group received oral normal saline for 28 days; RSV group received RSV (10 mg/kg; daily) via oral gavage; CIS group received a single dose of CIS (7 mg/kg; i.p.) on the 21st day; (CIS + RSV) group received both RSV and CIS by the same schedules and doses of RSV and CIS groups, respectively. Results demonstrated a significant decrease in MDA level and a significant increase in both glutathione content and activity of the antioxidant enzymes GPx, SOD, and CAT in the tissues of the ovary and uterus of CIS + RSV group in comparison to that of CIS group (P<0.05), also there are significantly decreased tissue levels of the proinflammatory cytokines and enzymes (NF-κB, IL-1β, IL-6, TNF-α, COX-2, and iNOS), increased estradiol, progesterone, prolactin and decreased FSH serum levels in CIS + RSV group compared to CIS group (P < 0.05). Moreover, there is downregulation of tissues Cleaved Caspase-3, NF-κB and Cox-2 proteins as shown in Western blot analysis, also apoptosis was significantly inhibited, evidenced by downregulation of Bax and upregulation of Bcl-2 proteins, and the ovarian and uterine histological architecture and integrity were maintained in CIS + RSV group compared to CIS group. In conclusion, these findings indicate that RSV has beneficial effects in ameliorating cisplatin-induced oxidative stress, inflammation, and apoptosis in the ovarian and uterine tissues of female rats.

Ibrahim MA ，Albahlol IA ，Wani FA ，Abd-Eltawab Tammam A ，Kelleni MT ，Sayeed MU ，Abd El-Fadeal NM ，Mohamed AA ... -  《-》

Zingerone ameliorates cisplatin-induced ovarian and uterine toxicity via suppression of sex hormone imbalances, oxidative stress, inflammation and apoptosis in female wistar rats.

Cisplatin (CP) is a widely used chemotherapeutic drug, effective against a variety of solid tumours, though its utility is limited due to its multiple organ toxicity. Zingerone (ZO), one of the most important components of dry ginger root, has several pharmacological activities, such as antioxidant, anti-inflammatory and anti-apoptotic properties. This study aimed to investigate the ameliorative effect of ZO on CP-induced ovarian and uterine toxicity in female rats. The rats were subjected to a prophylactic oral treatment of ZO (25 and 50 mg/kg body weight) for seven days to measure the protective effect against ovarian and uterine toxicity induced by a single (i.p.) of CP (7 mg/kg body weight) on the first day whereas the rats were sacrificed on the eighth day. The results showed that ZO decreased the serum FSH hormone level, increased the serum E2 hormone level, and also maintained the ovarian and uterine histological architecture and integrity. In addition, ZO obviously increased the measured activity of antioxidant enzymes (SOD, CAT and GPx) and the GSH content, and significantly reduced MDA levels. ZO was able to reduce the levels of the inflammatory markers NF-κB, TNF-α, IL-1β, IL-6, COX-2 and iNOS in CP-induced ovarian and uterine damage. It also inhibited apoptosis and reduced oxidative DNA damage markers by the downregulation of caspase-3 and 8-OHdG expression coupled with an upregulated Bcl-2 level. The results indicate that ZO may be beneficial in ameliorating CP-induced oxidative stress, sex hormone imbalances, inflammation and apoptosis in ovarian and uterine tissues of female rats.

Kaygusuzoglu E ，Caglayan C ，Kandemir FM ，Yıldırım S ，Kucukler S ，Kılınc MA ，Saglam YS ... -  《-》

Ameliorative effect of herbacetin against cyclophosphamide-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction.

Ijaz MU ，Mustafa S ，Batool R ，Naz H ，Ahmed H ，Anwar H ... -  《-》

Evidence of oxidative damage and reproductive dysfunction accompanying 4-vinylcyclohexene diepoxide exposure in female Wistar rats.

4-Vinylcyclohexene diepoxide (VCD) is an occupational chemical widely reported to deplete ovarian follicles in rodents. Here, we investigated VCD-induced reproductive dysfunction in female Wistar rats. The rats were orally administered with VCD (100, 250 and 500mg/kg) for twenty-eight days. Thereafter, we evaluated selected biomarkers of oxidative damage, inflammation, endocrine disruption, and apoptosis. We observed that VCD increased ovarian and uterine malondialdehyde (MDA) level, and catalase, glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities in rats (p<0.05). Also, VCD induced hormonal imbalance, increased ovarian superoxide dismutase (SOD) activity, and depleted uterine SOD activity and ovarian glutathione (GSH) level in rats (p<0.05). Lastly, VCD markedly increase immunohistochemical expressions of ovarian cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), Caspase-9 and Caspase-3. Overall, VCD induced reproductive dysfunctions in rats via ovarian and uterine oxidative damage, hormonal imbalance, as well as inflammation and apoptosis in the ovary of rats.

Abolaji AO ，Adedara IA ，Abajingin AO ，Fatunmibi OJ ，Ladipo EO ，Farombi EO ... -  《-》

Proanthocyanidin protects against cisplatin-induced oxidative liver damage through inhibition of inflammation and NF-κβ/TLR-4 pathway.

Although cisplatin (CIS) is a highly effective anticancer drug, hepatotoxicity is one of the most common adverse effects associated with its use. Recently, reactive oxygen species (ROS) and inflammation are suggested to be key factors in the pathophysiology of CIS-induced acute liver damage. The aim of this study is to investigate the possible protective effect of proanthocyanidin (PRO) against CIS-induced acute hepatotoxicity. Rats were divided into four groups: 1, Control; 2, PRO; 3, CIS; and 4, PRO + CIS. Biochemical studies and histopathology were used to assess liver damage. ROS, inflammatory cytokines, nuclear factor kappa beta (NF-κβ), inducible cyclooxygenase enzyme (COX-2), inducible nitric oxide synthase (iNOS), toll-like receptor-4 (TLR-4) gene expression, and apoptotic markers were also assessed. PRO pretreatment protected the liver against CIS-induced toxicity as indicated by decreased plasma levels of liver function enzymes and the normal liver histopathology observed in the PRO + CIS group. PRO pretreatment also diminished indicators of oxidative stress in the liver, including nitric oxide (NO) and malondialdehyde (MDA). It also increased the antioxidants, reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in the liver. Plasma interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) were all reduced. Liver gene expression of NF-κβ, COX-2, iNOS, and TLR-4 were all downregulated. Furthermore, PRO administration downregulated the liver expression of the apoptotic marker, Bax, while upregulated the antiapoptotic marker, Bcl2. In conclusion, our results revealed that PRO may protect against CIS-induced acute liver damage mainly through inhibition of ROS, inflammation, and apoptosis.

El-Shitany NA ，Eid B 《-》