Short-term exposure to gossypol causes reversible reproductive toxicity and nephrotoxicity in mice / 南方医科大学学报

OBJECTIVE@#To study the toxic effects of short-term exposure to gossypol on the testis and kidney in mice and whether these effects are reversible.@*METHODS@#Twenty 7 to 8-week-old male mice were randomized into blank control group, solvent control group, gossypol treatment group and drug withdrawal group. In the former 3 groups, the mice were subjected to daily intragastric administration of 0.3 mL of purified water, 1% sodium carboxymethylcellulose solution, and 30 mg/mL gossypol solution for 14 days, respectively; In the drug withdrawal group, the mice were treated with gossypol solution in the same manner for 14 days followed by treatment with purified water for another 14 days. After the last administration, the mice were euthanized and tissue samples were collected. The testicular tissue was weighed and observed microscopically with HE and PAS staining; the kidney tissue was stained with HE and examined for mitochondrial ATPase activity.@*RESULTS@#Compared with those in the control group, the mice with gossypol exposure showed reduced testicular seminiferous epithelial cells with rounded seminiferous tubules, enlarged space between the seminiferous tubules, interstitium atrophy of the testis, and incomplete differentiation of the spermatogonia. The gossypol-treated mice also presented with complete, non-elongated spermatids, a large number of cells in the state of round spermatids, and negativity for acrosome PAS reaction; diffuse renal mesangial cell hyperplasia, increased mesangial matrix, and adhesion of the mesangium to the wall of the renal capsule were observed, with significantly shrinkage or even absence of the lumens of the renal capsules and reduced kidney mitochondrial ATPase activity. Compared with the gossypol-treated mice, the mice in the drug withdrawal group showed obvious recovery of morphologies of the testis and the kidney, acrosome PAS reaction and mitochondrial ATPase activity.@*CONCLUSIONS@#Shortterm treatment with gossypol can cause reproductive toxicity and nephrotoxicity in mice, but these toxic effects can be reversed after drug withdrawal.

Impact and potential mechanism of human α-defensin 1 on low-density lipoprotein oxidation ability of ECV304 cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the role and potential mechanism of human α-defensin 1 (HNP-1) on low-density lipoprotein (LDL) oxidation ability of human endothelial cells (EVC304).</p><p><b>METHODS</b>Post incubation with LDL for 3 h, the malondialdehyde (MDA) and protein carbonyl (PCO) were detected in untreated ECV304 (control) and in HNP-1 transfected ECV304 in the presence and absence of siRNA against HNP-1. Flow cytometry and fluorescence microscopy were used to detect the generation of oxygen free radical in the ECV304 which have been pretreated by LDL, LPS and HNP-1, respectively.</p><p><b>RESULT</b>Compared with control group, MDA level was significantly increased in HNP-1 transfected [(4.21 ± 0.03) vs. (3.15 ± 0.02) nmol/mg · pro] or in HNP-1 stimulated ECV304 cells [(14.49 ± 1.10) vs. (9.47 ± 1.18) nmol/mg · pro], which could be significantly downregulated by siRNA [(3.76 ± 0.48) vs. (4.54 ± 0.28) nmol/mg·pro, all P < 0.05]. PCO was also significantly increased in HNP-1 transfected ECV304 cells. The levels of free radical were significantly increased in HNP-1 transfected or HNP-1 stimulated ECV304 cells.</p><p><b>CONCLUSION</b>HNP-1 can enhance the LDL oxidation ability of human endothelial cells via promoting the generation of free radicals.</p>