Cisplatin, despite its anti-cancer ability, exhibits severe testicular toxicities when applied systemically. Due to its wide application in cancer treatment, reduction of its damages to normal tissue is an imminent clinical need. Here we evaluated the effects of honokiol, a natural lipophilic polyphenol compound, on cisplatin-induced testicular injury. We showed in-vitro and in-vivo that nanosome-encapsulated honokiol attenuated cisplatin-induced DNA oxidative stress by suppressing intracellular reactive oxygen species production and elevating gene expressions of mitochondrial antioxidation enzymes. Nanosome honokiol also mitigated endoplasmic reticulum stress through down regulation of Bip-ATF4-CHOP signaling pathway. Additionally, this natural polyphenol compound diminished cisplatin-induced DNA breaks and cellular apoptosis. The reduced type I collagen accumulation in the testis likely attributed from inhibition of TGFβ1, αSMA and ER protein TXNDC5 protein expression. The combinatorial beneficial effects better preserve spermatogenic layers and facilitate repopulation of sperm cells. Our study renders opportunity for re-introducing cisplatin to systemic anti-cancer therapy with reduced testicular toxicity and restored fertility.

Cisplatin is a potent anti-cancer drug that has been widely used in the treatment of various cancers; however, cisplatin administration results in severe nephrotoxicity and impedes its clinical applications. In this study, we showed that honokiol, a polyphenol constituent extracted from Magnolia officinalis exhibited a short-term protective effect against cisplatin-induced damages in renal epithelial cells in vitro. The protective effects of honokiol were resulted from the combination of (1) reduced cellular oxidative stress ranging from 53 to 32% reduction during a 24-h incubation, (2) the maintenance of cellular antioxidant capacity and (3) the stabilization of cytoskeletal structure of the kidney epithelial cells. By promoting the polymerization of actin (1.6-fold increase) and tubulin (1.8-fold increase) cytoskeleton, honokiol not only maintained epithelial cell morphology, but also stabilized cellular localizations of tight junction protein Occludin and adhesion junction protein E-Cadherin. With stabilized junction protein complexes and structural polymerized cytoskeleton network, honokiol preserved epithelial cell polarity and morphology and thus reduced cisplatin-induced cell disruption and damages. Our data demonstrated for the first time that honokiol could counteract with cisplatin-induced damages in renal epithelial cells in vitro, future in vivo studies would further validate the potential clinical application of honokiol in cisplatin-based cancer treatments with reduced nephrotoxicity.

BackgroundSemen from the chimpanzee species becomes a colloidal solid after ejaculation. The formation of this copulatory plug is believed to prevent additional spermatozoa of subsequent mating events from accessing the ova. However, this naturally preserved strategy hampers the processes for sperm preparation. In this study, we investigated whether collagenase can be used to degelify the semen plug and accelerate the semen liquefaction process in zoo captive chimpanzee species (Pan troglodytes).ResultsWe showed that incubation of chimpanzee ejaculates with 0.1% type I collagenase efficiently and significantly (p < 0.05) releases 2.7-fold more spermatozoa from the coagulated ejaculates, and this degelification process did not alter sperm morphology or viability; nor did it stimulate spontaneous capacitation or an acrosome reaction as assessed by tyrosine phosphorylation and peanut agglutinin stains; moreover, based on computer assisted sperm analysis assay, motility-related parameters remained similar to those of untreated spermatozoa. When collagenase effects were evaluated on cryopreserved sperm samples, we observed post collagenase treatment in which 2.5% glycerol, as a cryoprotectant, preserved sperm acrosome integrity better than 7.8%; however, 7.8% glycerol, as a cryoprotectant, maintained sperm motility better than that of 2.5% glycerol.ConclusionsOur results demonstrated for the first time that type I collagenase can be used to obtain a significantly higher number of spermatozoa from colloid chimpanzee semen ejaculate without affecting the physiological properties of spermatozoa, and these results are critical for the subsequent gamete development. Our results would benefit sperm preparation processes and cryopreservation efficiency per ejaculate, as more unaffected spermatozoa can be released from the semen plug within a shorter period of time. These results would also benefit the genetic diversity of the chimpanzee species, using sperm cells from less dominant individuals, and for achieving better pregnancy success in primates with significantly higher amounts of sperm for artificial insemination.Electronic supplementary materialThe online version of this article (10.1186/s12917-018-1389-0) contains supplementary material, which is available to authorized users.