D proteins which further lead to oligozoospermia and abnormal spermatozoa. These findings support the results from other reports that DCA can seriously alter the testicles and reproductive tract in male rats [7, 9, 10]. Several studies have shown the ability of mature date fruits extract to increase sperm count, sperm motility, and viability [56] and to enhance spermatogenesis and increased the concentration of testosterone, FSH and LH [22] in intoxicated male rats. However, no study has been reported on the repro-protective effect of these fruits at besser stage of maturation. In the present study, the pretreatment with the ADE restored the testes and epididymis weights and histopathological alterations caused by DCA and TCA, in addition to retaining the control values of oxidative stress markers. The observed therapeutic potency of ADE might be due to several contributing factors, primarily including the mineral (zinc, selenium, copper, iron, calcium, cobalt, magnesium, manganese) PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28607003 and the GGTI298MedChemExpress GGTI298 vitamins (A, B, C) composition of these fruits [16]. Zinc is an acknowledged antioxidant factor that as well as being a core constituent of free radical scavenging enzymes such as SOD and a recognized protector of sulfhydryl groups is also thought to impair lipid peroxidation by displacing transition metals such as iron and copper from catalytic sites [57]. Selenium is an antioxidant trace element that is involved in the metabolism of free radicals and other substances produced by the oxidation of lipids in cell membranes. It also plays a role in metabolism in the liver and contributes to the maintenance of skeletal and cardiac muscles and sperm. Selenium is also a component of the majority of glutathione peroxidase antioxidant enzymes that are important in supporting the testicular function [1]. Vitamin C (ascorbic acid) contributes to the support of spermatogenesis at least in part through its capacity to reduce -tocopherol and maintain this antioxidant in an active state [58]. Vitamin C is itself maintained in a reduced state by a GSH-dependent dehydroascorbate reductase, which is abundant in the testes [59]. Deficiencies of vitamins C lead to a state of oxidative stress in the testes that disrupts both spermatogenesis and the production of testosterone [60]. The second mechanism by which aqueous date fruit extract protect testicles may be attributed to their richness in various polyphenolic compounds namely the flavonoids that are highly efficient against ROS-mediated injury [61]. The quercetin, a bioactive flavonoid component, of date fruit at this besser stage [62] may be one of the responsible of this observed protective effect. It was suggested that quercetin acts as an antioxidant by inhibiting oxidative enzymes such as xanthine oxidase, lipoxygenase, and NADPH oxidase. Inhibition of these enzymes is also responsible for the attenuation of oxidative stress as they play key rolesArem et al. BMC Pharmacology and Toxicology (2017) 18:Page 8 ofin the initial process of free radical-induced cellular damage [63]. It was recently reported that quercetin improved the antioxidants status in rats’ testes and prevented spermatogonial cells from oxidative stress damage caused by reproductive toxicants [64, 65]. In other way, a study reported by Michael et al. [66] showed that treatment of alloxan diabetic male rats with two diosmetin glycosides flavonoid compounds (diosmetin 7-O–L-arabinofuranosyl (1?) -D-apiofuranoside and diosmetin 7-O–D-apiofuranos.
