Zhenghong Zuo

Reduction of spermatogenesis in mice after tributyltin administration

Organotin compounds, such as tributyltin (TBT) used as an antifouling biocide, can induce masculinization in female mollusks. However, few studies addressing the effect of TBT on spermatogenesis in mammalian have been reported. This study was conducted to investigate the effects of TBT at low doses (0.5, 5, and 50 microg/kg, respectively) on spermatogenesis in mice as exposed from puberty and gave insight into the mechanism. After exposure for 30 days, the gonadosomatic index (GSI) was significantly decreased. The testosterone levels in the testes were not altered and the 17beta-estradiol levels were significantly decreased in a dose-dependent manner, spermatogenesis of the testis was significantly inhibited. Estrogen receptor (ER-alpha and ER-beta) levels in testes of the mice exposed to TBT were decreased in a dose-dependent manner. The results suggest that ER play an important role in TBT-mediated inhibition of spermatogenesis.

Antioxidant responses to benzo[a]pyrene, tributyltin and their mixture in the spleen of Sebasticus marmoratus

It has been reported that there is an interaction between Benzo[a]pyrene (BaP), a widespread carcinogenic polycyclic aromatic hydrocarbon, and tributyltin (TBT), an organometal used as an antifouling biocide. This study was therefore designed to examine the potential in vivo influence of BaP, TBT and their mixture on splenic antioxidant defense systems of Sebastiscus marmoratus. The fish were exposed to water containing environmentally relevant concentrations of BaP, TBT and their mixture. Spleens were collected for biochemical analysis after exposure for 7, 25, 50 d and after recovery for 7, 20 d. Cotreatment with BaP and TBT for 7 d potentiated the induction of glutathione peroxidase (GPx) activity by BaP or TBT alone. The cotreatment for 25 and 50 d resulted in inhibition of GPx activity, which was similar to the effect of TBT. Splenic glutathione S-transferase (GST) activities were significantly elevated in S. marmoratus exposed to BaP starting from 7 d and remained high up to 25 d. However, no further activity change was found with prolonged exposure. Cotreatment of BaP and TBT primarily inhibited the GST activity, which was similar to the effect of TBT. Cotreatment with BaP and TBT for 25 or 50 d potentiated the depletion of GSH (glutathione) by BaP or TBT alone. MDA (malondialdehyde) contents in spleen of S. marmoratus were not significantly altered compared with the control during the test period. Spleen, as an immune organ, is sensitive to exposure of BaP or TBT. It should have an effective mechanism to counteract oxidative damage. Antioxidative defense systems in spleen of S. marmoratus should be considered as potential biomarkers. Short-term exposure of BaP or TBT could result in induction of antioxidant defense system. A significant decrease of these indices, such as GSH, GST, GPx might indicate more severe contamination.

Relation of hepatic EROD activity and cytochrome P4501A level in Sebastiscus marmoratus exposed to benzo[a]pyrene

This study was designed to investigate the in vivo effects of benzo[a]pyrene (BaP) on hepatic ethoxyresorufin-O-deethylase (EROD) activity and its correlation with cytochrome P4501A (CYP1A) protein levels in Sebastiscus marmoratus, which were exposed through a water column to BaP (10, 100, 1000 ng/L, respectively) or were treated with intraperitoneal injections of BaP (0.5, 1, 5, 10 mg/kg, respectively) every 7 d. The results showed that after 25 d of waterborne exposure to 1000 ng/L BaP, fish hepatic CYP1A levels and EROD activity were significantly induced. In contrast, EROD activity was not altered 7 d after second intraperitoneal injections, whereas, CYP1A protein levels were increased. Dose-dependent increase of biliary BaP metabolites demonstrated that the catalytic activity ofCYP1A was induced by treatment with BaP. The lowest observable effect concentration with regard to biliary BaP metabolites (100 ng/L) was much lower than that with reference to EROD activity (1000 ng/L). The results suggest that biliary polycyclic aromatic hydrocarbon (PAH) metabolites were shown to better reflect the contamination gradients of PAHs than EROD activity. It appeared to be necessary to measure CYP1A protein levels to complement the EROD activity in relevant toxicological assessments.

Effects of tributyltin on epididymal function and sperm maturation in mice

The effects of tributyltin (TBT) on sperm parameters and epididymal function were investigated following oral doses of 0.5, 5 and 50μg/kg every 3 days for 45 days to male KM mouse. The TBT-treated groups showed a significant decrease in sperm counts and a significant increase in sperm abnormality both in a dose-dependent manner. The expression of matrilysin (MMP7) transcript in epididymis of mice exposed to TBT was significantly decreased in 5 and 50μg/kg group. There was a dose-dependent decline trend in the acid phosphatase activity, which somewhat relates with the TBT-induced increase in sperm abnormality. Acrosin and lactate dehydrogenase-X isoenzyme (LDH-X) activities from the cauda epididymal spermatozoa showed a dose-dependent decrease in the TBT groups. The result indicates a suppression of essential sperm maturational processes that precede the penetration of the oocyte by the sperm, such as capacitation and acrosome reaction. These results suggest that TBT could cause a spermatotoxic effects, the decline of sperm count and quality caused by TBT suggests that this chemical could impair fertility in animals.

Exogenous leptin promotes the recovery of regressed ovary in fasted ducks

The present study was undertaken to examine the effect of administered recombinant mouse leptin on the recovery of regressed ovary in fasted ducks. Twenty-eight ducks were divided into five groups: fed ad libitum (control; n=5), fasted control (FC; n=5), fasted+low dose of leptin (F+L; n=5), fasted+medium dose of leptin (F+M; n=5) and fasted+high dose of leptin (F+H; n=3). All four fasted groups were fasted for 2 days and then ad libitum and the ducks were treated with leptin at doses of 0 (control and FC), 50 (F+L), 250 (F+M) and 1000 (F+H) microg/kg body weight/day on day 3-5. Results showed that a moderate dose of leptin (250 microg/kg body weight/day) injected during the re-feeding period: (i) promoted the recovery of the regressed ovary as evidenced by an increase in ovary weight and recovery of yellow hierarchical follicles; (ii) elevated the plasma 17beta-estradiol (E(2)) level; (iii) increased the mRNA levels of ovary follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR) and estrogen receptor-beta (ER-beta). Furthermore, the results also showed that a high dose of leptin (1000 microg/kg body weight/day) may have a negative effect on the recovery of the regressed ovary. In conclusion, this study indicates that, in ducks, leptin may be involved in the recovery of the regressed ovary caused by 2 days of fasting. This effect may be related to increased plasma E(2) levels and stimulation of the mRNA levels of ovarian FSHR, LHR and especially ER-beta.

Antioxidant responses in Meretrix meretrix exposed to environmentally relevant doses of tributyltin

The effects on reduced glutathione (GSH) levels, glutathione-S-transferases (GST) and glutathione peroxidase (GPx) activities of digestive gland in Meretrix meretrix exposed to tributyltin (TBT) at environmental levels (0.1, 1, 10ng/L as Sn), in experimental condition, were evaluated. The GST activities in 0.1ng/L groups were significantly elevated after exposure for 2 days, and were significantly inhibited after exposure to 10ng/L TBT for 8 and 20 days. The GPx activities were mainly induced by TBT exposure, except the GPx activities in 10ng/L groups were significantly inhibited after exposure for 2 days. The GSH content was significantly decreased with prolonged exposure. The GSH content, GST and GPx activities in all exposure groups, transferred to clean recovery tanks for 20 days, were recovered to the level corresponding to that of the control group. Taken together, our present studies indicate that exposure to TBT may induce strong production of reactive oxygen species in the clams.

The concentration-dependent induction of cell death by trimethyltin chloride in rat liver epithelial IAR20 cells

In this study we intended to evaluate the cytotoxic and genotoxic effects of trimethyltin chloride (TMT), one of the most widely used organometallic compounds, on liver cells with the rat liver epithelial cell line IAR20. The results showed that TMT significantly inhibited cell growth in a concentration-dependent manner and caused an increase in DNA damage. Additionally, Hoechst 33342 staining and flow cytometry detected increases in apoptotic and necrotic cells. Western blots demonstrated that the Bcl-2 family of proteins was involved in the apoptotic process, but p53 was not concerned.