p,p'-DDT induces testicular oxidative stress-induced apoptosis in adult rats.

BACKGROUND: The 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) is a known persistent organic pollutant and male reproductive toxicant. The present study is designed to test the hypothesis that oxidative stress mediates p,p'-DDT-induced apoptosis in testis. METHODS: Male Wistar rats received an intraperitoneal (ip) injection of the pesticide at doses of 50 and 100mg/kg for 10 consecutive days. The oxidative stress was evaluated by biomarkers such lipid peroxidation (LPO) and metallothioneins (MTs) levels. Antioxidant enzymes activities was assessed by determination of superoxide dismutase (SOD), catalase (CAT) and hydrogen peroxide (H2O2) production. In addition, glutathione-dependent enzymes and reducing power in testis was evaluated by glutathione peroxidase (Gpx), glutathione reductase (GR), glutathione S-transferase (GST) activities and reduced and oxidized glutathione (GSH - GSSG) levels. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis. Germinal cells apoptosis and the apoptotic index was assessed through the TUNEL assay. RESULTS: After 10 days of treatment, an increase in LPO level and H2O2 production occurred, while MTs level, SOD and CAT activities were decreased. Also, the Gpx, GR, GST, and GSH activities were decreased, whereas GSSG activity was increased. Testicular tissues of treated rats showed pronounced degradation of the DNA into oligonucleotides as seen in the typical electrophoretic DNA ladder pattern. Intense apoptosis was observed in germinal cells of DDT-exposed rats. In addition, the apoptotic index was significantly increased in testis of DDT-treated rats. CONCLUSIONS: These results clearly suggest that DDT sub-acute treatment causes oxidative stress in rat testis leading to apoptosis.

Involvement of oxidative stress in the mechanism of p,p'-DDT-induced nephrotoxicity in adult rats.

The 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p'-DDT) is an organochlorine pesticide that persists in the environment and has a risk to human health. We investigated whether p,p'-DDT-induces nephrotoxicity in rats and whether oxidative stress and apoptosis are involved in the pathogenesis of this process. Male rats received the pesticide at doses of 50 and 100 mg/kg for 10 days. Renal damage was evaluated by histopathological examination and serum markers. The oxidative stress was evaluated by lipid peroxidation (LPO), metallothioneins (MTs) and protein carbonyl levels. Antioxidant enzymes were assessed by determination of superoxide dismutase (SOD) and catalase (CAT) activities. Glutathione-dependent enzymes and reducing power in kidney were evaluated by glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) activities. Renal tubular cells apoptosis was assessed through the TUNEL assay. After 10 days of treatment, an increase of serum creatinine and urea levels occurred, LPO and protein carbonyl levels were increased, while MTs level, SOD and CAT activities were decreased. Besides, the GPx, GR, GST, and GSH activities were decreased. Histological alterations in kidney tissue and intense apoptosis in renal tubular cells were observed. These results suggest that DDT sub-acute treatment causes oxidative stress and apoptosis, which may be the chief mechanisms of DDT-induced nephrotoxicity.

Effects of oral administration of 2,4-dichlorophenoxyacetic acid (2,4-D) on reproductive parameters in male Wistar rats.

The 2,4-dichlorophenoxyacetic acid (2,4-D) is used worldwide in agriculture as a selective herbicide. It has been shown to produce a wide range of adverse effects on the health of both animals and humans from embryotoxicity and teratogenicity to neurotoxicity. In the present study, we have examined the effect of 2,4-D on male reproductive function of rats. Male Wistar rats received daily by force-feeding 100 or 200 mg of 2,4-D/kg body weight for 30 consecutive days. Rats exposed to 100 and 200 mg of 2,4-D/kg showed a significant decrease in body weights only after 24 days of treatment and in relative weights of testis, seminal vesicles and prostate at killing day, when compared with controls. Moreover, a decrease in testosterone and an increase in FSH and LH serum levels were detected in treated rats. Besides, exposure to this herbicide induced pronounced testicular histological alterations with enlarged intracellular spaces, tissue loosening and dramatic loss of gametes in the lumen of the seminiferous tubules. In addition, a decreased motility and a number of epididymal spermatozoa with an increased sperm abnormality rate were found in treated rats in comparison with control. With the highest dose, histological observations of seminal vesicles indicated a considerable decrease of secretions in the lumen, a thinness of the muscle layer surrounding the epithelium with branched mucosal crypts and reduced luminal space. In prostate, the heights of the cells decreased while acinar lumen were enlarged and they lost the typical invaginations. Our results suggest that a subacute treatment of 2,4-D promotes reproductive system toxicity.

Mechanisms of chromium hexavalent-induced apoptosis in rat testes.

Hexavalent chromium (CrVI)-containing compounds, present in industrial settings and in the environment, are known as carcinogens and mutagens. The present study is designed to test the hypothesis that oxidative stress mediates CrVI-induced apoptosis in testis. Male Wistar rats received an intraperitoneal injection of potassium dichromate at doses of 1 and 2 mg kg-1. Superoxide anion production was assessed by the determination of the reduction of cytochrome c and iodonitrotetrazolium, lipid peroxidation (LPO), metallothioneins (MTs), and catalase (CAT) activity. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis. Germinal cells apoptosis was detected by toluidine blue staining. The expression of Bax and Bcl-2 proteins (Pts) was also investigated. After 15 days of treatment, an increase of LPO and MT levels occurred, while CAT activity was decreased. Testicular tissues of treated rats showed pronounced degradation of the DNA into oligonucleotides as seen in the typical electrophoretic DNA ladder pattern. Intense apoptosis was observed in germinal cells of Cr-exposed rats. Bax Pt expression was induced in spermatogonia and spermatocytes cells of CrVI-treated rats. In contrast, Bcl-2 Pt was occasionally observed in germ cells of CrVI-exposed rats. These results clearly suggest that CrVI subacute treatment causes oxidative stress in rat testis leading to apoptosis.

Hexavalent Chromium-Induced Apoptosis in Rat Uterus: Involvement of Oxidative Stress.

The present study is designed to test the hypothesis that oxidative stress mediates hexavalent chromium (VI)-induced apoptosis in uterus. Female Wistar rats received an intraperitoneal (i.p.) injection of potassium dichromate at doses of 1 and 2 mg/kg. Superoxide anion production was assessed by determination of the reduction of cytochrome c and iodonitrotetrazolium (INT), lipid peroxidation (LPO), metallothioneins (MTs), and catalase (CAT) activity. The expression of Bax and Bcl-2 proteins was investigated. After 15 days of treatment, an increase of LPO and MT levels occurred, whereas CAT activity decreased. Intense apoptosis was observed in endometriotic stromal cells of Cr-exposed rats. Bax protein expression was induced in endometriotic stromal cells with 1 mg of Cr(VI)/kg, and in stromal and epithelial cells at the higher dose. These results clearly suggest that Cr(VI) subacute treatment causes oxidative stress in rat uterus, leading to endometriotic stromal cells apoptosis.

Effects of hexavalent chromium on reproductive functions of male adult rats.

Hexavalent chromium is an environmental contaminant which may be associated with reproductive abnormalities in male rats. In the present study, we examined the effect of hexavalent chromium on male reproductive function of rats. Male Wistar rats received a daily intraperitoneal injection of potassium dichromate (1 or 2 mg/kg body weight) for fifteen consecutive days. A decrease in testis weight and an increase in seminal vesicles and prostate weights were demonstrated after chromium treatment. Moreover, a dose-dependent increase in blood and testis chromium levels as well as an increase in FSH and a decrease in LH and testosterone serum levels were detected in treated rats. Histological analysis revealed pronounced morphological alterations with enlarged intracellular spaces, tissue loosening and dramatic loss of gametes in the lumen of the seminiferous tubules of treated rats. In addition, a decreased sperm motility and number of epididymal spermatozoa together with an increased sperm abnormality rate was found in chromium-treated rats in comparison to controls. In rats receiving the higher chromium dose, histological images presented considerably increased areas filled with seminal vesicle and prostate secretions. The mucosal crypts of seminal vesicles and the typical invaginations of prostate were altered. The results suggest that subacute treatment of potassium dichromate promotes reproductive system toxicity and affects testicular function of adult male rats.

Embryotoxicity and fetotoxicity following intraperitoneal administrations of hexavalent chromium to pregnant rats.

Heavy metals are omnipresent in the environment, and industrial use has greatly increased their presence in soil, water and air. Their inevitable transfer to the human food chain remains an important environmental issue as many heavy metals cause a range of toxic effects, including developmental toxicity. Administration of chromium VI (1 and 2 mg/kg as potassium dichromate) through intraperitoneal (i.p.) injection during organogenesis (days 6 to 15 of gestation) in rats revealed embryo- and fetotoxic effects. Reduced fetal weight, retarded fetal development, number of fetuses per mother and high incidences of dead fetuses and resorptions in treated mothers were also observed. Gross morphological abnormalities, such as displayed form of edema, facial defect, lack of tail, hypotrophy, severs subdermal haemorrhage patches and hypotrophy of placenta were observed in fetuses after chromium VI-treated mothers. A skeletal development of fetuses presented an incomplete ossification in nasal, cranium, abdominal or caudal bones in rats treated with 1 mg/kg of chromium, whereas rats treated with 2 mg/kg showed ossification and absence of the sacral vertebrae compared with the control. At a higher dose of chromium, histological changes were found in fetuses with atrophy of theirs vital organs. Placental histological observations revealed a pronounced morphological alteration, with atrophy of decidual cells, a degenerated of chorionic villi and hypertrophy of blood lacuna. The present study suggests a risk to the developing embryo when the mother is exposed to a high concentration of chromium VI during organogenesis.

Both aluminum and polyphenols in green tea decoction (Camellia sinensis) affect iron status and hematological parameters in rats.

BACKGROUND: Green tea leaves naturally contain high levels of polyphenols and aluminum (Al). Polyphenols in green tea decoction are considered to be one of the major factors responsible of low iron status. However, the effects of Al from green tea decoction on iron status and hematological parameters remained unclear. AIM OF THE STUDY: The objective was to investigate the Al absorption from green tea decoction and studied its influence on iron status and hematological parameters in rats. METHODS: During the experiment period, rats were given the experimental diet + a simple dose of Al sulfate with or without graded doses of green tea decoction (25, 50 and 100 g/l). The Al absorption was evaluated in the serum; however, iron status was evaluated by the iron concentration in the liver, kidney, spleen and femur. In addition, the hemoglobin and hematocrit were evaluated. RESULTS: Our results showed that the serum Al significantly increased between 61.5 and 342%, as tea doses-dependant. The Al sulfate significantly decreased the reserve of iron in all studied organs between 21.7 and 17% (P < 0.05). In groups receiving green tea decoction alone or Al + graded doses of tea, the reserve of iron significantly decreased in all studied organs between 59.4 and 18.5% (P < 0.01). Al alone or associated with drinking doses of tea significantly decreased hemoglobin concentration between 23.6 and 9% (P < 0.05) and hematocrit between 12.7 and 7% (P < 0.01). CONCLUSION: Our data showed that Al from green tea decoction was more absorbed in the serum than Al sulfate. Al absorption was associated with low iron status and reduction of hemoglobin and hematocrit. Considering that Al competes with iron in different stage of erythropoiesis including transferrin binding, so we could assume that the negative effect of tea on iron status arises not only from polyphenols iron complexes but also from Al released in tea decoction.

Effect of green tea decoction on long-term iron, zinc and selenium status of rats.

AIMS: The objective was to examine the effect of green tea decoction given at two different concentrations on the long-term (6 weeks) iron, zinc and selenium status of rats. METHODS: During the experimental period, the rats were given ad libitum a basic diet + ultra pure water (control group), a basic diet + green tea decoction prepared from 50 g/l (tea 50 group), or a basic diet + green tea decoction prepared from 100 g/l (tea 100 group). The zinc and iron status was evaluated by determining their concentrations in the serum, blood precipitate, liver, spleen, femur, heart and kidney. Selenium status was evaluated by the serum selenium concentration and whole blood glutathione peroxidase activity. RESULTS: Green tea decoction significantly reduced serum iron by 26% in the tea groups (p < 0.01). The blood precipitate of iron was significantly decreased by 25 and 41% in the tea 50 and tea 100 groups (p < 0.01), respectively. The reserve of iron stored in the liver, spleen and femur was significantly reduced in the tea 100 group by 32% (p < 0.02), 20% (p < 0.04) and 35% (p < 0.005), respectively. Moreover, the two concentrations of green tea significantly decreased the reserve of iron stored in the kidney (p < 0.005) and heart (p < 0.02). In contrast with its effects on iron status, green tea decoction significantly increased the serum zinc in the tea 100 group by 24% (p < 0.001). It also increased the blood precipitate of zinc by 50 (p < 0.01) and 75% (p < 0.0001) in tea 50 and tea 100 groups, respectively. In the kidney, heart and femur, zinc significantly increased in the tea groups dependent on the tea dose. Similarly, the high concentration of green tea decoction significantly increased the serum selenium concentration by 16% (p < 0.004). In addition, both concentrations of green tea decoction significantly increased the whole blood glutathione peroxidase activity by 102 and 130% (p < 0.01). CONCLUSION: Green tea decoction reduced the iron status and improved the zinc and selenium status of rats. These effects may constitute another beneficial effect of the green tea decoction which could play an important role in the antioxidant processes.