Neila Marouani

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.

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.

Mechanisms of chromium hexavalent-induced apoptosis in testis rats

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.

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

BackgroundThe 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.MethodsMale 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.ResultsAfter 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.ConclusionsThese results clearly suggest that DDT sub-acute treatment causes oxidative stress in rat testis leading to apoptosis.

Adverse Haemato-Biochemical Effects of Chlorinated Insecticide in Adult Male Rats.

Khemais Ben Rhouma. The 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (p,p’-DDT) is a highly toxic organochlorine pesticide and posing adverse effects on the environment and public health due to its frequent usage in developing countries. The present study is aimed to investigate the effects of p,p’-DDT exposure on some hematological and biochemical parameters, as well as, histopathological changes in liver. Male Wistar rats received an intraperitoneal (ip) injection of the pesticide at doses of 50 and 100mg/kg for 10 consecutive days. The hematological parameters were evaluated by the level of red blood cells (RBC), white blood cells (WBC), platelet count (PLT), hemoglobin (Hb) and hematocrit (Ht). The biochemical parameters such as liver glycogen, blood glucose, triglycerides (TG) and plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels were determined. In addition, histological changes in the liver, proliferating cell nuclear antigen (PCNA) and proliferation index (PI) were analyzed. After 10 days of treatment, hematological analysis revealed a significant increase of RBC, Hb and Ht levels while WBC and PLT counts were significantly decreased. Also, the liver glycogen and TG contents were decreased, whereas blood glucose, ALT, AST and LDH levels were increased. Histopathological examination of the liver revealed pronounced morphological alterations with cytoplasmic vacuolation, focal necrosis, sinusoidal congestion, infiltration of inflammatory leucocytes and loss of hepatic structure in periportal areas of treated rats. Immunohistochemical staining showed an increase in PCNApositive cells in liver of treated rats. In addition, the PI and the percentage of binucleated hepatocytes cells were significantly increased in liver of DDTtreated rats. These results clearly suggest that DDT sub-acute treatment causes extensive changes in hematological and biochemical parameters leading to liver damage.

DDT-Induced Hypothyroidism Mechanisms in Rats

DDT and many of its metabolites have been linked to endocrine disruptions because of their capacity for mimicking or interfering with endogenous hormones and other signaling chemicals of the endocrine system.