Phenytoin-induced toxicity in the postnatal cerebellar development in rat: effect of calotropis procera on selective biochemical and haematological variables

Phenytoin, an antiepileptic drug is used in managing seizures. Phenytoin-associated oxidative stress causes cellular damage by the generation of free radicals. Vitamin C, a standard antioxidant and Calotropisprocera are believed to scavenge oxygen free radicals. The effect of C. procera extract on haematological and biochemical variables in an in-vivo model was studied. Pregnant rats were administered phenytoin (50 mg/kgbody weight). Extracts of C. procera (300 mg/kg body weight) and vitamin C (200 mg/kg body weight) were administered one hour prior to phenytoin treatment separately, while control animals received tap water only.The animals had access to food and water ad libitum. Blood was collected from animals on day 50 postpartum for packed cell volume (PCV), haemoglobin (Hb) content and evaluation of levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) evaluation. Lipid peroxidase (LPO) and reduced glutathione (GSH) levels in the cerebellum were assessed as markers of oxidative stress on day 50 postpartum. Phenytoininduced toxicity was associated with increased cerebellar LPO and decreased GSH levels. Increase in ALT andAST levels in the serum was observed. However, PCV and Hb levels were not affected. LPO, GSH, ALT and AST levels registered a tendency to shift towards normalcy on administration of C. procera and vitamin C tophenytoin. In conclusion, supplementation with C. procera leaf extract reduced the rate at which phenytoin induced toxicity in developing rat cerebellum postnatally

Cyfluthrin-induced hepatotoxicity in rats

The hepatotoxic effect of continous administration of cyfluthrin was investigated in rats. Rats (Rattus norvegicus) were grouped into A (0 ppm) control, B (100 ppm) and C (200 ppm) with the indicatedamount of cyfluthrin administered orally for 15 weeks.The hepatotoxicity level was assessed by monitoring the changes in the organ to body; weight ratio, micronutrient level (iron, zinc, copper andselenium), the nutritional status (total carbohydrate, total glucose, total protein, total amino acids, total lipid and total cholesterol), the lipid peroxidation level (reduced glutathione and thiobarbiturate) and theantioxidant enzyme activities (glutathione peroxidase, glutathione reductase, catalase, and glucose-6-phosphate dehydrogenase). A dose-dependent decrease in the organ-to-body ratio was observed. Themicronutrient level in the test groups increase significantly. The total carbohydrate, total glucose, total amino acids and total protein show a significant decrease in the test groups. There is no significantdifference observed in the tissue cholesterol at both dosages under investigation. Lipid peroxidation was increased in the test groups as indicated by a significant increase in the thiobarbiturate level and asignificant decrease in the reduced glutathione level. All the antioxidant enzymes studied increased significantly. Cyfluthrin is potentially hepatotoxic under continuous administration in rats

Review: Environmental endocrine disruptors of testicular function

In the last 50 years the incidence of infertility, testicular and prostate cancers and associated maladies has increased significantly. Infertility now affects 15-20% of couples as opposed to 7-8% fifty years ago. Average sperm counts among adult men have decreased by 50% since 1938, with a decline of 2% every year from 1973. This decline in male reproductive health has been linked to an increased presence in the environment of chemical contaminants in the form of pesticides and plastics. Rapid and unplanned industrialization caused large amounts of these synthetic compounds and their by-products to be released in the environment (air, soil, water and food). studies have shown that occupational exposure to pesticides caused neonatal deaths, congenital defects, testicular dysfunction and male infertility. Many of these chemicals found in our environment and households have oestrogenic properties (“xenoestrogens”) and are toxic because they affect the endocrine system (“endocrine disruptors”). Evidence of the health hazards of endocrine disrupting chemicals continues to mount. In terms of male fertility, it now seems that these ubiquitous chemicals are a significant threat at various stages, from testicular development to sperm production to the functionality of healthy sperm. This class of chemicals appears to be threatening male fertility on several fronts. That endocrine disruptors abound in our environment is not in doubt. Clinicians and other health practitioners confronted with the challenges of managing male infertility should attempt to identify the aetiology of a possible exposure to endocrine disruptors, and initiate a plan to control and prevent exposure to others. In addition, concerted efforts should be made by both government and non-governmental agencies to institute local studies that will assess local endocrine disruptors, degree of contamination, level of exposure and proffer control and preventive measures. Emphasis should be placed on establishment of chemical screening and testing program, research into dose and vulnerable periods, institution of surveillance of disease incidence, improvement of exposure monitoring, and educating community leaders and the public in general. Keywords: Endocrine disrupt ors, testis, testosterone, environment, infertility, peticides

&#946-Tocopherol (vitamin E) attenuates the testicular toxicity associated with experimental cryptorchidism in rats

Cryptorchidism is the most frequent anatomic anomaly observed in an endocrine gland. It is a wellidentified risk factor in infertility and testicular cancer. It is believed that increased generation of freeradicals and oxidants play an important role in the resulting testicular damage. The present study investigated the role of a-tocopherol (vitamin E) as an antioxidant in protecting the testis againstdamage in experimental cryptorchidism. Thirty six Sprague - Dawley rats weighing 250 – 280 g were divided into three groups; A, B and C, with Group A (intact rats) as control. All rats in Group B and Cwere rendered bilaterally cryptorchid by anchoring the upper pole of testis to the anterior abdominal wall. Group C rats in addition received vitamin E at 25 mg/kg body weight intramuscularly daily. Fifty sixdays after cryptorchidism induction, bilateral testicular weight, bilateral testicular volume, bilateral caudal epididymal sperm characteristics, bilateral testicular histology and serum hormone levels wereall tested. Most of the above parameters were significantly lower (P < 0.05) in Groups B and C compared to Group A. The testes of vitamin E treated cryptorchid rats had better functional and histologicalprofiles than those of the untreated cryptorchid rats. Experimental cryptorchidism did not affect the plasma testosterone levels. The results indicated that vitamin E moderated the deleterious effects ofexperimental cryptorchidism

Reversal of experimental varicocele-induced testicular toxicity by L-ascorbate in rats

Varicoceles are the abnormal tortuosity and dilatation of the veins of the pampiniform plexus that drain the testis. Varicoceles are variously considered the commonest “correctable” cause of infertility or thecommonest “reported” cause of infertility depending on individual viewpoint. Even though the pathophysiology of testicular damage in varicocele has not been completely understood, there is anincreasing body of evidence pointing towards the role of reactive oxygen species (ROS) and oxidative stress in the pathogenesis of varicocele related subfertility. In this study we investigated the role of Lascorbate(vitamin C) as an antioxidant in rejuvinating the testis following its damage in experimental varicocele. Thirty male Sprague- Dawley weighing 150-200 g were divided into three groups. While thefirst group had sham operations, experimental varicoceles were established by complete ligation of the left and right main spermatic vein in the later two groups. The third group in addition to varicoceleinduction had daily gavage administration of 8 mg/kg body weight vitamin C for fifty six days. All animals were sacrificed by decapitation fifty six days after varicocele induction. Testicular weights,testicular volumes, caudal epididymal sperm characteristics, testicular histology and serum hormone levels were evaluated. Results showed that the testes of the rats that were given vitamin C postexperimental varicocele had better physiological, biochemical and histological profiles than those of the untreated animals. These results indicate the potency of vitamin C for modulating testicular toxicityin varicocelized animals

Effects of Short and Medium Term use of Artesunate on Fertility in Male Rats

The effects of artesunate on major sperm parameters and testicular history in wistar rats were examined. Sixteen sexually mature wistar rats weighing 150-180gm were divided into 4 groups and administered 2mg/kg or 1mg/kg of the drug for period ranging 2-8weeks. Control animals were administered water only. All animals were allowed food and water ad-libitum. At the end of these periods, the animals were euthanized and their cauda epididymes, testes, prostrate and seminal vesicles were neatly removed from them. Major sperm parameters were obtained from the epididymal sperm and the testis prepared and examined histologically. Results showed normal to raise sperm parameters in both groups treated for 2 weeks. Sperm density in millions/gm of testes in groups 2 and 3 which received different doses of the drug for 2 weeks was 62.0+10.2 and 65.6+13.8 respectively compared to 52.1+11.0 in control rats. However after 4 weeks on the drug all major parameters were significantly depressed. Sperm density was 20.3+1.5 and abnormal sperm rate 71.7% compared to 52.1+11.0 and 26.7+2.3% in control animals respectively. This study suggests that under certain conditions, artesunate will suppress spermatogenesis. Until exhaustive studies of the drug\'s effects on fertility are accomplished, it must be used with appropriate caution in young people. Keywords: Artesunate, spermatogenesis, sperm parameters. Nigerian Journal of Health and Biomedical Sciences Vol. 7 (2) 2008: pp. 18-2