Guoliang Zhou

Protective Effect of Lycium barbarum Polysaccharides Against Doxorubicin‐induced Testicular Toxicity in Rats

The present study aimed to investigate whether Lycium barbarum polysaccharides (LBP) would protect against doxorubicin (DOX)‐induced testicular toxicity. Male Sprague‐Dawley rats were treated with distilled water (4 mL/kg) or LBP (200 mg/kg, p.o.) daily for 10 days and followed by saline (0.9 %, 10 mL/kg) or DOX (10 mg/kg) intravenous injection at day 7. Pretreatment with LBP ameliorated DOX‐induced reduction in the testicular weights, sperm concentrations and percentage of motile sperms, as well as the increase in abnormal sperm rate. LBP administration to DOX‐treated rats successfully reversed the changes in MDA and GHS‐Px levels. Compared with the control, pretreatment with LBP significantly increased the plasma testosterone level in the LBP + DOX group. The histopathology examinations further confirmed that LBP effectively attenuated DOX‐induced severe degenerative changes of seminiferous tubules. This study illustrated the capability of LBP in attenuating testicular oxidative stress and protecting testis‐specific toxicity in DOX‐exposed rats. Copyright

Nanoparticle Delivery Systems Reduce the Reproductive Toxicity of Docetaxel in Rodents

Various docetaxel (DTX)-loaded nanoparticle delivery systems have been designed to enhance the solubility and pharmacological effects of DTX. However, the toxicity changes of these nano-modified DTX (nano-DTX) are not yet clear enough. Herein, to compare the reproductive toxicity between conventional DTX and nano-DTX, we performed sperm toxicity test in mice, and fertility and early embryo-fetal developmental toxicity test in rats. It was found that DTX severely repressed spermatogenesis and sperm motility, and dramatically increased sperm abnormality in mice and rats. Moreover, DTX significantly decreased copulation, conception and fertility indexes in rats, and no positive pregnant female rat was obtained after treatment with DTX. However, nano-DTX significantly reduced DTX-induced toxicity to sperm. Most importantly, nano-DTX obviously converted DTX-induced fertility and early embryo-fetal developmental toxicity. Furthermore, organ weights and histopathology examination revealed DTX, but not nano-DTX, significantly decreased testis and epididymis weights, and induced obvious histopathological atrophy of testes and epididymides in rats. Further studies indicated that changed activity of lactate dehydrogenase C4 (LDH-C4) in rodents testes was mainly responsible for the above observations. These results strongly support the idea that DTX-loaded nanoformulations have the potential to overcome the reproductive toxicity of DTX.

Chmp1A acts as a tumor suppressor gene that inhibits proliferation of renal cell carcinoma

Renal cell carcinoma (RCC) is a highly malignant and often fatal disease of the kidney. Chmp1A is a member of the Endosomal Sorting Complex Required for Transport (ESCRT-III) family, and plays a role in the cytoplasm in sorting proteins to the multivesicular body (MVB). Chmp1A functions as a tumor suppressor gene and has been reported in pancreatic tumor cells. Here, we examined the expression level of Chmp1A in human RCC tissues and renal tumor cells by real-time quantitative RT-PCR and western blot. We found that the expression level of Chmp1A is significantly lower in RCC tissues and renal tumor cells compared with adjacent non-tumorous tissues and normal renal cells. Additionally, inhibition of Chmp1A expression by shRNA induced tumor formation in normal renal cells. However, inhibition of Chmp1A did not significantly affect tumor cell proliferation in vitro and tumor progression in vivo. Interestingly, overexpression of Chmp1A using a eukaryotic plasmid inhibited the proliferation of renal tumor cells in vitro and the growth of renal tumor in vivo. Thus, our results demonstrate that Chmp1A functions as a tumor suppressor gene in renal cells and may be a useful target for treatment of RCC.