Zhenqiang You

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

Protective effect of Salvia miltiorrhizae injection on N(G)-nitro-D-arginine induced nitric oxide deficient and oxidative damage in rat kidney.

N(G)-nitro-D-arginine (d-NNA) could convert into N(G)-nitro-L-arginine (l-NNA) in vivo, and kidney is the major target organ. In the chiral inversion process, a number of reactive oxygen species (ROS) were generated and NOS activity was inhibited, which may cause renal damage. Salvia miltiorrhiza (SM), a traditional Chinese drug, was used in the treatment of cardiovascular diseases and chronic renal failure. The aim of the present study was to investigate the kidney damage caused by D-NNA administration for 12 weeks and to evaluate the effects of treatment with SM on D-NNA-induced kidney damage. The rats, induced with D-NNA for period of 12 weeks, showed significant elevation of Blood Urea Nitrogen (BUN), Creatinine (Crea) and MDA levels, and significant decrease of SOD and GSH-Px activities, as compared with control group. In addition, the kidney of rats induced with D-NNA only showed remarkable histopathology, including severe mononuclear cell infiltration, mild tubular dilatation and congestion, and moderate interstitial desmoplasia. After 4 weeks SM treatment, the activity of SOD, GSH-Px and iNOS and the production of NO were significantly higher (P<0.05), and the levels of BUN, Crea and MDA were significantly lower than that of D-NNA only group (P<0.05). In addition, treatment with SM showed histopathological protection in tubular dilatation, congestion, mononuclear cell infiltration and interstitial desmoplasia. The present results indicate that the toxicity of D-NNA relates to its ability to generate oxidative stress and upregulate NOS activity in rat kidney. SM probably ameliorates D-NNA-induced nephrotoxicity in rats according to scavenging free radical and upregulating NOS activity.

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.

Role of Quzhou Fructus Aurantii Extract in Preventing and Treating Acute Lung Injury and Inflammation

Quzhou Fructus Aurantii (QFA) is an authentic herb of local varieties in Zhejiang, China, which is usually used to treat gastrointestinal illnesses, but its effects on respiratory inflammation have not been reported yet. In our study, the anti-inflammatory activity of QFA extract (QFAE) was evaluated on copper sulfate pentahydrate (CuSO4·5H2O)-induced transgenic neutrophil fluorescent zebrafish model. QFAE showed a significant effect of anti-inflammation in CuSO4·5H2O-induced zebrafish by reducing the neutrophil number in the inflammatory site. We investigated the anti-inflammatory activity of QFAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice models and RAW 264.7 cells. QFAE had an anti-inflammatory effect on reducing total cells, neutrophils, and macrophages in BALF and attenuated alveolus collapse, neutrophils infiltration, lung W/D ratio, myeloperoxidase (MPO) protein expression and other pulmonary histological changes in lung tissues, as well as hematological changes. Levels of pro-inflammatory cytokines, including TNF, IL-6, IFN-γ, MCP-1, and IL-12p70, were decreased, whereas anti-inflammatory cytokine IL-10 was increased after treatment with QFAE both in vivo and in vitro. In summary, our results suggested that QFAE had apparent anti-inflammatory effects on CuSO4·5H2O-induced zebrafish, LPS-induced ALI mice, and RAW 264.7 cells. Furthermore, QFAE may be a therapeutic drug to treat ALI/ARDS and other respiratory inflammations.

Potential accumulation of protopanaxadiol-type ginsenosides in six-months toxicokinetic study of SHENMAI injection in dogs

Abstract SHENMAI injection (SMI), derived from famous Shen Mai San, is a herbal injection widely used in China. Ginsenosides are the major components of SMI. To monitor the exposure level of SMI during long‐term treatment, a 6‐month toxicokinetic experiment was performed. Twenty‐four beagle dogs were dived into four groups (n = 6 in each group): a control group (0.9% NaCl solution) and three SMI groups (2, 6 or 3 mg/kg). The dogs were i.v. infused with vehicle or SMI daily for 180 d. Blood samples for analysis were collected at specific time points as follows: pre‐dose (0 h); at 10, 30, and 60 min during infusion; and at 10, 30, 60, 90, 120, 240, and 300 min post‐administration. Concentrations of ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 in the plasma were determined simultaneously by liquid chromatography–tandem mass spectrometry. Non‐compartmental parameters were further calculated and analyzed. Significant differences were found between the kinetic behavior of 20(S)‐protopanaxadiol‐type (PPD‐type) and 20(S)‐protopanaxatriol‐type (PPT‐type) ginsenosides. Increasing in the exposure level of PPD‐type ginsenosides was observed in dogs during the experiment. Therefore, PPD‐type ginsenosides are closely related to the immunity modulation effect of SMI. Increased PPD‐type ginsenoside exposure level may present potential toxicity and induce drug‐drug interaction risks during SMI administration. As such, PPD‐type ginsenoside accumulation must be carefully monitored in future SMI research. Graphical abstract Figure. No Caption available. HighlightsThe exposure level and TK/PK profile of SMI were obtained in dogs.Great differences were found between the kinetic of PPD and PPT type ginsenosides.Potential accumulation of PPD‐type ginsenoside was proved in dogs.