Nanoparticle Delivery Systems Reduce the Reproductive Toxicity of Docetaxel in Rodents

Abstract

Various docetaxel (DTX)-loaded nanoparticle delivery systems have been designed to enhance the solubility and pharmacological e®ects of DTX. However, the toxicity changes of these nano-modi¯ed 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 signi¯cantly decreased copulation, conception and fertility indexes in rats, and no positive pregnant female rat was obtained after treatment with DTX. However, nano-DTX signi¯cantly 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, signi¯cantly 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.

Shark Liver Oil Protects the Chromosome and Sperm of Mice against the Cytotoxicity of Taxotere

“…MCF-7 resistant cells showed amplification of chromosomes 7, 17 and 18, and the deletion in chromosomes 6, 10, and 12. MDA-MB-231 resistant cells showed a gain of chromosomes 5, and 9, and loss of chromosomes 4, 8,10, 11, 12and 18 [17]. Also, Taxotere caused head abnormalities of mice sperms like without hook and hammer shape head and also caused tail abnormalities in sperm like a coiled tail.…”

BMP4 Cooperates with Retinoic Acid to Induce the Expression of Differentiation Markers in Cultured Mouse Spermatogonia

“…BMP4 is well-documented to be necessary for the generation and survival of PGCs and might therefore be involved in the regulation of spermatogenesis [ 22 , 24 , 25 , 60 ]. Whereas BMP4 alone is unable to induce the formation of PGCs, BMP8b is required for BMP4-induced PGC formation in cultured epiblasts [ 61 ].…”

Functionalized graphene oxide-based thermosensitive hydrogel for near-infrared chemo-photothermal therapy on tumor

“…The mice were administrated different preparations with the same dosage of DTX (10 mg/kg) every three days for four times. 29 For the Laser group, the treatments were the same as described above except that 808 nm NIR laser irradiation (2.5 W) was performed for 1 min once a day during the therapy. The body weight and tumor sizes were measured before administration, and tumor volume (V) was calculated according to the formula: V = [length × (width) 2 ]/2.…”