Mitigating effects of some antidotes on fluoride and arsenic induced free radical toxicity in mice ovary.

The effects of oral administration of sodium fluoride (NaF) and/or arsenic trioxide (As(2)O(3)) (5 mg and 0.5 mg/kg body weight, respectively) for 30 days were investigated on free radical induced toxicity in the mouse ovary. The reversibility of the induced effects after withdrawal of NaF+As(2)O(3) treatment and by administration of antioxidant vitamins (C, E) and calcium alone as well as in combination were also studied. The combined treatment of NaF and As(2)O(3) impaired significantly (p<0.001) the production of free radical scavengers such as glutathione and ascorbic acid as well as antioxidant enzymes, namely, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (Cat), thereby increasing ovarian lipid peroxides (LPO) which might have rendered the ovary susceptible to injury. The withdrawal of the combined (NaF and As(2)O(3) for 30 days) treatment caused partial recovery in the ovary, which was more pronounced (p<0.001) by treatment with vitamin C, calcium, or vitamin E alone and in combination. Hence the induced toxicity was transient and reversible.

Effects of fluoride on the histoarchitecture of reproductive organs of the male mouse.

The effects of sodium fluoride (NaF) ingestion in two doses (10 and 20 mg/kg body weight) for 30 days on histology and histocytometry of reproductive organs of the adult male mouse were investigated. In order to study reversibility, treatment was withdrawn for one and two months. The testes, epididymides, vas deferens, prostate, and seminal vesicle were utilized for the study by standard hematoxylin-eosin staining and an ocular eye piece and micrometer scale. NaF treatment caused severe disorganization and denudation of germinal epithelial cells of seminiferous tubules with absence of sperm in the lumina. The Leydig cell and nucleus diameters were not affected. The caput epididymis showed fewer changes than the cauda. However, epithelial cell nuclear pyknosis and absence of luminal sperm were observed. A reduction in epithelial cell height, nuclear pyknosis, denudation of cells, and absence of sperm occurred in the cauda epididymis. The vas deferens epithelium showed nuclear pyknosis, clumped stereocilia, and cell debris but no sperm in the lumen and an increase in the lamina propria. The prostate and seminal vesicles were not affected by treatment. Withdrawal of treatment caused marked recovery in the histoarchitecture of these organs. The effects of NaF treatment are therefore transient and reversible.

In vitro fluoride toxicity in human spermatozoa.

Effects of sodium fluoride (NaF) on washed, ejaculated human spermatozoa at doses of 25, 50, and 250 mM were investigated in vitro at intervals of 5, 10, and 20 min. Sodium fluoride (NaF) did not affect the extracellular pH of sperm, except that a slight acidification was caused by the 250 mM dose only. The treatment caused a significant enhancement in acid phosphatase (ACPase) and hyaluronidase activities after 5 and 10 min. However, the decrease in the lysosomal enzyme activity after 20 min treatment could have been due to the gradual increase in fluoride accumulation by spermatozoa leading to membrane damage. Silver nitrate staining of sperm revealed elongated heads, deflagellation, and loss of the acrosome together with coiling of the tail. Sperm glutathione levels also showed a time-dependent decrease with complete depletion after 20 min indicating rapid glutathione oxidation in detoxification of the NaF. The altered lysosomal enzyme activity and glutathione levels together with morphologic anomalies resulted in a significant decline in sperm motility with an effective dose of 250 mM.

Microdose vasal injection of sodium fluoride in the rat.

A single microdose (50 micrograms/50 microL) injection of sodium fluoride (NaF) into the vasa deferentia of adult male albino rats (Rattus norvegicus) caused arrest of spermatogenesis and absence of spermatozoa in the lumina of the seminiferous tubules of the testes, which consequently led to a decline in the sperm count in the caudae epididymides. Scanning electron microscopy of cauda and vas deferens sperm revealed deflagellation and tail abnormalities. This is probably related to the alterations in the internal milieu of these organs which rendered the spermatozoa immotile and consequently caused fertility impairment in the experimental animals. Thus microdoses of sodium fluoride were found to affect reproductive function and fertility rate.

Effects of crude aqueous extract of Carica papaya seeds in male albino mice.

The effect of an aqueous extract of Carica papaya seeds (5 mg/kg body/day im and 20 mg/kg body wt/day oral) were investigated in male mice treated for 60 days. Reversibility studies were also carried out to elucidate if any induced effects were transient. The aqueous extract did not manifest any estrogenic effects in male mice, and LD50 studies indicated its nontoxic nature. The body weight or the weights of reproductive organs, kidney, and adrenal were not affected, indicating that the extract did not promote body weight gain through obesity or water retention. The serum SGOT, SGPT, protein, and cholesterol levels were also within the normal range in the extract-treated mice, suggesting that the extract does not influence liver function or cholesterol and protein metabolism. These data suggest that the aqueous extracts of papaya seeds is safe and could serve as an effective male contraceptive in rodents.

Role of ascorbic acid on mercuric chloride-induced genotoxicity in human blood cultures.

Efforts are made to find therapeutic agents capable of minimizing genotoxicity of various natural and man-made compounds. The genotoxicity induced by mercury compounds remains controversial. Therefore we have investigated the genotoxic effect of mercuric chloride (MC; HgCl(2)) at three concentrations (1.052, 5.262 and 10.524 microM) and role of L-ascorbic acid (vitamin C) at a concentration of 9.734 microM on MC-treated short-term human leucocyte cultures. We assessed the proliferative rate index (PRI), sister chromatid exchange (SCE) and chromosomal aberrations (CAS) in control and MC-treated cultures with and without vitamin C supplementation. The results showed that MC has no effect on cell-cycle kinetics, but the frequency of SCE/cell was significantly higher in a dose-dependent manner than control values. HgCl(2) also significantly induced C-anaphases (abnormal mitosis) in blood cultures. These effects were prevented by the addition of vitamin C to MC-treated cultures. The data indicate the mutagenic activity of MC and the protective role of vitamin C on mercury-induced genotoxicity in human blood cultures is probably due to its strong antioxidant and nucleophilic nature.

Three siblings with Harlequin Ichthyosis in an Indian family.

The Harlequin fetus is a distinct genetic entity with a strikingly grotesque appearance. Three siblings (two males, one female) with Harlequin Ichthyosis, a rare form of congenital disorder, born to the same parents are presented. The genetic aspects are discussed and the relevant literature is reviewed.

Effect of papaya seed extract on microenvironment of cauda epididymis.

AIM: To evaluate the effect of aqueous Carica papaya seed extract on microenvironment of cauda epididymis. METHODS: Adult male albino rats were intramuscularly administered with 0 (control) or 0.5 mg papaya seed extract/kg body weight for 7 days. Cauda epididymal tubular content was collected by micropuncture technique; epididymal luminal fluid and sperm pellets were separately analyzed. RESULTS: The results revealed that the extract treatment caused significant reduction, as compared with control, in total protein and sialic acid contents in both epididymal fluid and sperm pellet. As compared with control, significantly lowered acid phosphatase activity was recorded in sperm pellet but was higher in epididymal fluid after the treatment. The extract treatment also caused significant reduction in level of inorganic phosphorus in the epididymal fluid. CONCLUSION: It is concluded that the aqueous papaya seed extract alters cauda epididymal microenvironment.

Effect of papaya seed extract on contractile response of cauda epididymal tubules.

AIM: To evaluate the administration of Carica papaya seed extract on the contractility of cauda epididymal tubules in male rats. METHODS: Adult male albino rats were administered intramuscularly papaya seed extract at a dose of 0.5 mg/kg/day for 7 days. Animals were killed, cauda epididymal tubules of 5 cm length were isolated and the contractile response to different concentrations of adrenalin (1-500 microg/25mL) was examined. In another group of animals, the contractile response was assayed 3 months after withdrawal of the treatment. RESULTS: Papaya seed extract brought about a significant decrease in the contractile response of epididymal tubules as compared with the control. After three months of papaya withdrawal, a nearly normal pattern of contraction was regained. CONCLUSION: Papaya seed treatment reversibly reduces the contractile response of cauda epididymal tubules.

Effect of estradiol benzoate on reproductive organs and fertility in the male rat.

The effects of estradiol benzoate (E2B) at a dose of 50 micrograms/day per rat for 7, 15 and 24 days on some androgenic parameters, viz. organ weights including those of pituitary, succinate dehydrogenase, acid phosphatase, fructose, cholesterol and protein of epididymis, vas deferens, accessory glands and fertility in male rats were investigated. The semen characteristics and standard electron microscopy (SEM) study on sperm morphology of cauda epididymis were also carried out. The results revealed that most of the androgenic parameters were decreased by E2B administration, whereas the accumulation of cholesterol and protein occurred in testis and epididymis due to androgen deprivation to target organs. This deprivation effect also led to a reduction in testicular and cauda epididymal sperm population, loss of motility in the latter and an increase in number of abnormal spermatozoa, thereby manifesting 100% failure in fertility in treated animals. Moreover, these effects were related to the duration of the treatment. Thus, the estradiol benzoate showed androgen antagonistic and antifertility effects in rats.

Preliminary studies on manganese free radical in vasectomy.

PIP: Electron spin resonance spectrometric studies of Mn2+ free radical in the cauda epieymal sperm suspensions of normal, vasectomized and vasectomized plus ascorbic acid treated rats were conducted. In each case, the characteristic 6 hyperfine line-spectrum of g=2.003 at a magnetic field of 3390 gauss was obtained. Healthy adult male albino rats of the Holtzman strain were used for the experiments. Analysis of the spectra showed that the spin concentrations of free radical of the experimental groups were not significantly different from those of the control. Bilateral vasectomy was performed by the standard technique used in human beings. The rats were divided into 3 groups: normal intact control; bilaterally vasectomized for 10 days; and, bilaterally vasectomized and given ascorbic acid orally (100 mg/day/animal) for 10 days. The sperm suspensions were prepared in a known volume of .9% saline solution. Equal amounts of 10% PCA were added to the sperm suspension. Considering the importance of Mn2+ in various reproductive functions, it is evident that vasectomy does not affect the utilization of Mn2+ by epididymis.^ieng

Effects of CdCl2 on the secretory functions of sex accessory glands of rats.

PIP: The effects of cadmium chloride (Cd) alone (1 mg given as a single injection) or in combination with ascorbic acid (AA; 100 mg/day for 10 days) on the secretory functions of sex accessory glands of rats were studied in healthy male albino rats. Animals were sacrificed after 10 days treatment and the seminal vesicles (SVs), dorsolateral prostate (DLP), ventral prostate (VP), bulbourethral glands (BU), and coagulating glands (CO) were excised and weighed. Weight of all accessory glands were decreased by 10 days treatment with Cd. Cd + AA gave similar results. AA concentration increased in all glands and was significantly increases in CO (p less than .01). Levels of ascorbogin increased in all glands except CO and BU and in the latter a significant (p less than .001) increase was found. The rate of AA utilization increased significantly (p less that .001) in the accessories. A significant (p less than .001) reduction in the activity of succinate dehydrogenase was observed in Cd-treated rats with a further reduction with combined treatment. Alkaline phosphatase decreased (p less than .001) after Cd treatment but AA in combination restored it to control levels. Cd increased acid phosphatase (p less than .001) and was further activated by Cd + AA. Phosphorylase activity was elevated with Cd (p less than .001) but recovery occurred in SV and BU with Cd + AA. Glycogen increased (p less than .001; .01) with both treatments as did citric acid. Protein results were inconsistent with Cd but activation was found in most glands under combined treatment. The results reveal that most androgen-dependent biochemical constituents and organ weights were affected significantly by a single injection of Cd. AA had a protective and beneficial influence on the restoration of structural integrity and metabolism in sex accessory glands.^ieng