The protective effect of crocin on cisplatin-induced testicular impairment in rats

Background Side effects of cisplatin (CIS) such as testicular toxicity restrict its clinical use. Instead, evidence indicates that crocin (CR) has synergistic anti-cancer potential with CIS and exhibited beneficial effects on CIS-induced hepatorenal damage. The aim of this study was to investigate the protective potential of CR against CIS-induced testicular toxicity in rats. Methods Fifty adult male Wistar rats randomly assigned to five equal groups including control, CIS, and CIS plus CR at doses of 6.25 mg/kg (CIS + CR6.25), 25 mg/kg (CIS + CR25), and 100 mg/kg (CIS + CR100). CIS and CIS + CR groups received a single intraperitoneally (i.p.) injection of CIS (7 mg/kg). CR (6.25–100 mg/kg i.p.) injections were started three days before the CIS injection and continued once a day for up to 13 days. On the 14th day, all animals were sacrificed and their blood samples and testes were removed for biochemical and histological analyses. Results Compared to the control group, CIS significantly decreased relative testis weight (0.28 vs. 0.39, p < 0.001), testosterone level (0.3 vs. 2.31 ng/mL, p < 0.001), germinal layer area (25,886 vs. 35,320 µm2, p < 0.001), superoxide dismutase (SOD) (0.9 vs.1.73 U/mg, p < 0.001) and increased testicular lipid peroxidation (3.05 vs. 15.35 nmol/mg, p < 0.001). CR at 25 mg/kg ameliorated testicular lipid peroxidation and enhanced SOD activity compared to CIS group (p < 0.05). Besides, CR treatment at the maximum dose (100 mg/kg) resulted in reversing CIS effects on testis weight, testosterone level, SOD, lipid peroxidation, and germinal layer area. Conclusions These findings demonstrated that CR co-treatment could prevent CIS-induced testicular toxicity in rats.

Aristolochic acid I induces impairment in spermatogonial stem cell in rodents

Aristolochic acid I (AAI) is a natural bioactive substance found in plants from the Aristolochiaceae family and impairs spermatogenesis. However, whether AAI-induced spermatogenesis impairment starts at the early stages of spermatogenesis has not yet been determined. Spermatogonial stem cells (SSCs) are undifferentiated spermatogonia that balance self-renewing and differentiating divisions to maintain spermatogenesis throughout adult life and are the only adult stem cells capable of passing genes onto the next generation. The objective of this study was to investigate whether AAI impairs SSCs during the early stages of spermatogenesis. After AAI treatment, we observed looser, smaller and fewer colonies, decreased cell viability, a decreased relative cell proliferation index, and increased apoptosis in SSCs in a concentration- and/or time-dependent manner. Additionally, AAI promoted apoptosis in SSCs, which was accompanied by upregulation of caspase 3, P53 and BAX expression and downregulation of Bcl-2 expression, and suppressed autophagy, which was accompanied by upregulation of P62 expression and downregulation of ATG5 and LC3B expression, in a concentration-dependent manner. Then we found that AAI impaired spermatogenesis in rats, as identified by degeneration of the seminiferous epithelium, and increased apoptosis of testicular cells. Taken together, our findings demonstrate that AAI causes damage to SSCs and implicate apoptosis and autophagy in this process. The impairment of SSCs may contribute to AAI-induced testicular impairment. Our findings provide crucial information for the human application of botanical products containing trace amounts of AAI.

Monosodium glutamate (MSG):promoter of neurotoxicity, testicular impairment, inflammation and apoptosis in male rats

Monosodium glutamate (MSG) is one of the most common food additives extensively used as a flavor enhancer. MSG induced lipid peroxidation and inflammation. The present study aimed to assess the neurotoxicity, testicular impairment, inflammation and apoptosis induced by MSG. Thirty adult male Wistar rats, weighing about 180-200 g were assigned equally into five groups, each consists of six rats. Animals of Group I are controls and they received distilled water, whereas animals of Groups II, III, IV and V were given oral daily doses of MSG 0.8, 1, 2 and 3 g/kg body weight, respectively for consecutive 70 days. Administration of different doses of MSG revealed a significant elevation in the levels of malondialdehyde (MDA), nitric oxide (NO), β amyloid 1-42, proinflammatory cytokines (IL-6, TNF-α), cholesterol and sperm abnormality while it showed reduction in the level of GSH and SOD, CAT and GST antioxidant enzymes activities, sperm count and sperm motility. MSG led to disruption in neurotransmitter levels; serotonin, norepinephrine, glutamate and GABA, also disorders in sexual hormones; testosterone, FSH and LH. The present results were confirmed by histological and immunohistochemical observations that obviously designate the neurodegeneration and reproductive toxicity. In conclusion, administration of low and high doses of MSG provoke deleterious effects on oxidant/ antioxidant markers, neurotransmitters, inflammatory cytokines, sexual hormones, brain and testes structures. Prominence hazards of lasting exposure to low and high doses of MSG on neuronal and testicular health. Therefore, its use should be restricted.