Effect of repeated oral administration of quinalphos on blood esterases in Bubalus bubalis

The effect of quinalphos on blood esterases was investigated in male buffalo calves after daily oral doses of 0.7, 1.4 and 2.1 mg/kg body weight for 28 consecutive days. Quinalphos markedly inactivated serum carboxylesterase (69-90%) and plasma cholinesterase activity (75-88%). Esterase activities in animals receiving 0.7 mg/kg/day of quinalphos approached normal levels 14 days after the termination of its ingestion. The results suggest that quinalphos is an effective inhibitor of blood esterases in vivo and its repeated exposure to buffaloes may impair detoxification of organophosphorus insecticides that are mainly biodegraded by carboxylesterase enzyme.     

Fetotoxic response of technical quinalphos in rats.

Technical Quinalphos was administered po to pregnant rats through day 6-20 of gestation at doses of 0.5 or 1.5 mg/kg body weight. Quinalphos produced enzymatic changes in liver and serum of dams associated with mild pathomorphological changes in liver and brain. Fetotoxic effects were not observed at the tested dose levels as determined by total number of implantations, percentage resorption, live fetuses, crown rump length and fetal weight. A few insignificant skeletal deformities were noticed. A significant inhibition of acetylcholinesterase activity in fetal brain and placenta indicated possible transmigration of quinalphos from dams to fetuses.     

Assessment of the no-observed-effect level (NOEL) of quinalphos in pregnant rats.

Technical quinalphos (0.5, 1.5, 2, 3 or 4.5 mg/kg body weight) was administered orally to pregnant rats from day 6-15 of gestation. At 3 and 4.5 mg/kg/day, quinalphos produced significant changes in hepatic ALT, ALP and serum ALT, AST, ALP and LDH activity along with hepatocellular changes in dams. The AchE activity in brain and red blood cells was also significantly inhibited at these two doses. At 0.5, 1.5 and 2 mg/kg/day, however, quinalphos did not produce any such changes. Up to a dose of 2 mg/kg/day there was no foetotoxic or teratogenic effect, as evidenced by number of implantation sites, percent resorption, foetal weight, morphological, visceral and skeletal evaluations. Hence, 2 mg/kg body weight of quinalphos could be considered as the no-observed-effect level (NOEL) on foetal and maternal toxicity in rats.     

Antigenotoxic effect of nordihydroguaiaretic acid against chlormadinone acetate-induced genotoxicity in mice bone-marrow cells

Nordihydroguaiaretic acid (NDGA), a phenolic lignan, was tested for its antigenotoxic potential against chlormadinone acetate (CMA)-induced genotoxic damage in mice bone-marrow cells. Doses of about 22.50 mg/kg body weight of CMA were given along with 1, 5 and 10 mg/kg body weight of NDGA intraperitoneally. The treatment resulted in the reduction of sister chromatid exchanges and chromosomal aberrations induced by CMA, suggesting an antigenotoxic potential of NDGA. Earlier studies show that CMA generates reactive oxygen species, responsible for genotoxic damage. The free radical-scavenging property of NDGA is responsible for the reduction of genotoxic damage induced by CMA in mice bone-marrow cells.     

Testicular and spermatotoxic effects of quinalphos in rats

Testicular and spermatotoxic effects were investigated in rats exposed to technical-grade quinalphos (70%) at dose levels of 0.52 mg kg(-1) (1/50th ld(50)) or 1.04 mg kg(-1) body weight (1/25th ld(50)) for 5 days a week for 60 days. The activities of marker testicular enzymes such as sorbitol dehydrogenase (SDH) and acid phosphatase were significantly decreased but those of lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and beta-glucuronidase were significantly increased in a dose-dependent manner. This particular pattern in the activity of testicular-cell-specific enzymes, a decrease in sperm motility and total epididymal sperm count and an increase in abnormal sperm suggest damage to germ cells and Sertoli cells. The testicular and spermatotoxic effects observed in rats may be due to the pesticide quinalphos or its metabolites.     

Mutachromosomal effects of tert-butylhydroquinone in bone-marrow cells of mice

When given to mice either in a single ip injection of 200 mg/kg body weight or in 30 daily oral doses of 2 mg/kg, tert-butylhydroquinone had severe clastogenic effects on the bone-marrow cells. However mitostatic activity was observed only with the acute treatment.     

Antispermatogenic and antifertility effects of 20,25-diazacholesterol dihydrochloride in mice

The effect of intraperitoneal administration for 28 days of 10, 20, and 30 mg/kg body weight per day of 20,25-diazacholesterol dihydrochloride (SC 12937), a hypocholesterolemic agent, on the testis of Parkes (P) strain mice was investigated. Histologically, testes in mice treated with 10 or 20 mg/kg body weight of SC 12937 showed non-uniform degenerative changes in the seminiferous tubules as both affected and normal tubules were observed in the same section; the affected tubules showed intraepithelial vacuolation, occurrence of giant cells, exfoliation of germ cells, and marginal condensation of chromatin in round spermatids. In both dosage groups, only 11-12% of the seminiferous tubules were affected, and no significant differences were found in the frequency of affected tubules between the two groups. By contrast, testes in mice treated with 30 mg/kg body weight of the drug exhibited a degenerated appearance of germ cells in all seminiferous tubules. The treatment also had adverse effects on motility, viability, morphology, and number of spermatozoa in the cauda epididymidis, and on fertility. Even 56 days after drug withdrawal, the above parameters remained markedly affected. Our results thus suggest that SC 12937 treatment causes antispermatogenic and antifertility effects in P mice and that the effects are not reversible up to 56 days after drug withdrawal. This compound may prove useful in the control of rodent populations.     

Histopathological changes induced by quinalphos in the testes and liver of Indian dessert gerbils, Meriones hurrianae (Jerdon)

Single intraperitoneal injection of quinalphos (15 mg/kg body weight) produced several pathological changes in the testes and liver of the Indian desert gerbil, Meriones hurriane (Jerdon). The degenerative changes included testicular atrophy, reduction in tubular size and enlarged interstitium. In the spermatogenic cells, necrosis and karyopycnosis were observed. Hepatic cells revealed cytoplasmolysis, vacuolation and necrosis. The nuclei of the hepatocytes showed karyorrhexis and karyolysis.     

Lack of synergistic effect between arsenic, mercury and ethyl methane sulfonate on the frequency of chromosomal aberrations in mice

The influence of arsenic and mercury on the frequency of chromosome aberrations induced by ethylmethane sulfonate was studied in mice. No synergistic effects could be demonstrated in somatic and germ cells of mice given a combined treatment of arsenic trioxide solution (As2O3, 12 mg per kg body weight) or of mercuric chloride solution (HgCl2, 6 mg per kg body weight) with ethylmethane sulfonate (EMS, 200 mg per kg body weight).     

Genotoxic evaluation for the tricyclic antidepressant drug, amitriptyline

Tryptizol(?) [amitriptyline HCl (AT); El-Kahira Pharmacological and Chemical Co., Cairo, Egypt], a widely used antidepressant drug in Egypt, was evaluated for its genotoxicity. The evaluation was performed in somatic (bone marrow) and germ (spermatocytes) cells, as well as well as the sperm morphology (i.e., head and tail) and count of the resulting sperm. Three doses were tested (low, medium, and high); they were chosen according to the drug manufacturer. The low-dose group received orally 1?mg/kg body weight (b.w.) daily for a total period of 1 month; the medium-dose group received 1?mg/kg b.w. daily for 15 days and 2?mg/kg b.w. daily for another 15 days; and the high-dose group received 1?mg/kg b.w. daily for 10 days, then 2?mg/kg b.w. daily for another 10 days and, finally, 4?mg/kg b.w. daily for 10 more days. The results showed that AT treatment induced structural and numerical chromosome abnormalities in somatic cells (bone marrow) and germ cells (spermatocytes). Moreover, AT significantly reduced both the mitotic index and meiotic activity after the different treatments used. AT was found to increase significantly the incidence of sperm-cell head and tail abnormalities. The sperm-cell count was also significantly decreased with the 3 doses tested. In general, results of chromosome abnormalities in both somatic and germ cells as well as sperm morphology and count showed that the effect of AT was dose dependent. The results of the current study showed that AT is a genotoxic agent for both somatic and germ cells and should be taken under special precautions and medical supervision.     

Radioprotective Efficacy of Aloe vera Leaf Extract

Radiomodifying effects of the leaf extract of Aloe vera were observed on the testes of Swiss albino mice at 50 and 100 mg/kg dose levels. This extract was non-toxic when injected up to 800 mg/kg, and significant enhancement in survival time of the irradiated group was observed. In addition, treatment reduced radiation-induced damage to germ cells and loss in body weight.     

Genotoxicity of chlordiazepoxide hydrochloride on the bone-marrow cells of Swiss mice

The mutagenic effect of chlordiazepoxide hydrochloride was evaluated in the bone-marrow cells of Swiss mice by the micronucleus test. A comparative study of the drug was made by oral and intraperitoneal administrations containing 187.5, 375 and 562 mg/kg body weight and 67, 134 and 201 mg/kg body weight respectively, corresponding to three sublethal doses of 1/4, 1/2, and 3/4 LD50, respectively. Bone-marrow preparations were made and slides scored for the presence of micronuclei in the developing erythrocytes. The results showed that the drug chlordiazepoxide induced a significant increase of micronuclei in the polychromatic erythrocytes by both routes of administration.     

Short-term prophylaxis with deoxyspergualin prevents testicular autoimmunity in mice

The effects of the treatment with the immunosuppressant deoxyspergualin on the development of experimental autoimmune orchitis were studied. The results showed that C3H/He mice immunized with testicular germ cells and treated daily with either 0.3 or 3 mg/kg body weight deoxyspergualin during days 15-20 post-immunization developed experimental autoimmune orchitis lesions with a significantly lower incidence and severity than did the control mice treated under the same experimental conditions with phosphate buffered saline (PBS). The effects of deoxyspergualin were clearly dose-dependent, and the higher dose of the drug also markedly reduced the degree of delayed type hypersensitivity responses against testicular germ cells. These data suggest that deoxyspergualin may be worthy of consideration for the prevention/treatment of human immunoinflammatory orchitis.     

GAVAGE ADMINISTRATION OF THE FUNGAL TOXIN FUMONISIN B TO FEMALE SPRAGUE-DAWLEY RATS

The fungal toxin fumonisin B (FB ) is a contaminant of corn-based foods and feeds pro1 1 duced by members of the genus Fusarium. Fumonisin B toxicity was examined using gav1 age administration of purified toxin to female Sprague-Dawley rats. For 11 consecutive days each rat received a single dose of FB at the following concentrations: control 1 (saline), 1, 5, 15, 35, or 75 mg FB /kg body weight/d. Significantly depressed body 1 weight and food consumption occurred at 35 and 75 mg FB /kg/d. By the end of the dos1 ing period there were no significant changes in food consumption. Kidneys and bone marrow were most sensitive to FB exposure. Changes in renal morphology were observed 1 from 5 to 75 mg FB /kg/d, accompanied by transient changes in urine osmolality and 1 urine enzyme levels. Increased cellular vacuolation was the primary change associated with bone-marrow toxicity, starting at doses of 5 mg FB /kg/d. Hepatotoxicity was indi1 cated by reduced liver weight, elevated serum alanine amonitransferase (ALT), and mild histopathological changes occurring at doses of 15 mg FB /kg/d and higher. Increased 1 cytoplasmic vacuolation of adrenal cortex cells occurred in rats treated with 15 mg FB /kg/d and higher, indicating that the adrenals are also potential targets of FB . Elevated 1 1 serum cholesterol, which is a consistent response to FB was observed at 5 mg FB /kg/d 1, 1 and higher. Based on responses in this study, gavage is an appropriate substitute for longer feeding studies. Compared to previous work with male rats, gender-related differences in FB responses lacked consistency but indicated that males may be marginally 1 more sensitive than female Sprague-Dawley rats.     

Genotoxic evaluation for the tricyclic antidepressant drug,amitriptyline

Tryptizol^® [amitriptyline HCl (AT); El-Kahira Pharmacological and Chemical Co., Cairo, Egypt], a widely used antidepressant drug in Egypt, was evaluated for its genotoxicity. The evaluation was performed in somatic (bone marrow) and germ (spermatocytes) cells, as well as well as the sperm morphology (i.e., head and tail) and count of the resulting sperm. Three doses were tested (low, medium, and high); they were chosen according to the drug manufacturer. The low-dose group received orally 1?mg/kg body weight (b.w.) daily for a total period of 1 month; the medium-dose group received 1?mg/kg b.w. daily for 15 days and 2?mg/kg b.w. daily for another 15 days; and the high-dose group received 1?mg/kg b.w. daily for 10 days, then 2?mg/kg b.w. daily for another 10 days and, finally, 4?mg/kg b.w. daily for 10 more days. The results showed that AT treatment induced structural and numerical chromosome abnormalities in somatic cells (bone marrow) and germ cells (spermatocytes). Moreover, AT significantly reduced both the mitotic index and meiotic activity after the different treatments used. AT was found to increase significantly the incidence of sperm-cell head and tail abnormalities. The sperm-cell count was also significantly decreased with the 3 doses tested. In general, results of chromosome abnormalities in both somatic and germ cells as well as sperm morphology and count showed that the effect of AT was dose dependent. The results of the current study showed that AT is a genotoxic agent for both somatic and germ cells and should be taken under special precautions and medical supervision.     

Anticlastogenic activity of morin against whole body gamma irradiation in Swiss albino mice

Anticlastogenic activity of morin was explored against whole body gamma radiation, at a dose rate of 1.66 Gy/min in Swiss albino mice pretreated intraperitoneal or orally. Pretreatment with morin 10, 25, 50, 75, 100, 125, and 150 mg/kg, i.p. delayed and reduced percentage mortality and increased mean survival times in mice irradiated with 10 Gy gamma radiation. Intraperitoneal route was found superior to oral route. An i.p. dose of 100 mg/kg was found to be the most effective dose in preventing radiation-induced weight loss, increasing the mean survival times and reducing percentage mortality. Morin (100 mg/kg) pretreatment effectively maintained spleen index (spleen weight/body weight x 100) and stimulated endogenous spleen colony forming units. Pretreatment with morin (100 mg/kg) significantly reduced dead, inflammatory, and mitotic cells in irradiated mice jejunum along with a significant increase in goblet cells and rapidly multiplying crypt cells. Morin (100 mg/kg) also maintained the villus height close to normal, prevented mucosal erosion and basement membrane damage in irradiated jejunum. Nuclear enlargement in epithelial cells of jejunum was lower in morin treated mice compared to radiation control. Morin (100 mg/kg) also significantly elevated the endogenous antioxidant enzymes viz. glutathione S transferase (GST), superoxide dismutase (SOD) and reduced glutathione (GSH), in normal mice at 2, 4 and 8 h post treatment. Drastic decrease in endogenous enzymes (GSH, GST, catalase and SOD) and total thiols was observed in irradiated mice at 2, 4 and 8 h post irradiation, while pretreatment with morin (100 mg/kg) prevented this decrease. Morin (100 mg/kg) also elevated radiation LD(50) from 9.2 to 10.1 Gy, indicating a dose modifying factor (DMF) of 1.11.     

Testicular cytotoxicity of DA-125, a new anthracycline anticancer agent, in rats

To assess the testicular cytotoxicity induced by DA-125, a new anthracycline anticancer agent, 50 male Sprague Dawley rats were randomly assigned to five groups, with 10 rats in each group, and were given different single intravenous doses of DA-125 at dose levels of 0, 6.25, 12.5, 25, and 50 mg/kg body weight. On Day 56 after treatment, all male rats were killed and necropsied. Parameters of testicular cytotoxicity included genital organ weights, testicular sperm head counts, epididymal sperm motility and morphology, repopulation index, epididymal index, and histopathologic examinations. At 25 and 50 mg/kg, the weights of testes, epididymides, and seminal vesicles were reduced dose-dependently, but prostate weight was not different among the groups. At 50 mg/kg, the number of testicular sperm heads was decreased. However, the motility and morphology of epididymal sperm were comparable to the control values. On histopathologic examination, atrophy of seminiferous tubules, loss or decrease of germ cells, formation of multinucleated giant cells, and/or vacuolization of Sertoli cells in the testis were observed at 25 and 50 mg/kg. In addition, decreased sperm content and increased degenerative germ cells in the ductus epididymis were also found. Some recovery of spermatogenesis was observed at 25 mg/kg, whereas a decline in the repopulation index was observed at 50 mg/kg, indicating that the surviving stem cells had become unable to produce differentiated germ cells to enter the spermatogenic pathway. There was no evidences of testicular cytotoxicity at 6.25 and 12.5 mg/kg. These results indicate that administration of a single dose of DA-12.5 (25 to 50 mg/kg) results in testicular damage in male Sprague-Dawley rats.     

Assessment of in vivo mutagenic potency of ethylenediaminetetraacetic acid in albino mice.

Ethylenediaminetetraacetic acid (EDTA) disodium salt, a widely used metal chelator, was studied for its potency to induce bone marrow micronuclei, dominant lethal mutations and sperm-head abnormalities in albino mice. The acute oral LD₅₀ dose computed by probit regression was 30 mg/kg body weight in the strain used. Preliminary studies showed that oral administration of EDTA disodium salt at doses of 5, 10 and 15 mg/kg body weight/day on 5 consecutive days did not induce any obvious signs of toxicity. In the bone marrow micronucleus assay acute doses of EDTA disodium salt (5–20 mg/kg body weight) induced a dose-dependent increase in the incidence of micronucleated polychromatic erythrocytes at a 24-hr sampling. However, administration at doses of 5, 10 and 15 mg/kg for 5 consecutive days did not produce any observable effect on either the testicular or epididymal weights and histology. No appreciable alterations were observed in the caudal sperm counts at any of the sampling intervals and there was no treatment-related increase in the incidence of sperm-head abnormalities. Furthermore, treatment of male mice with EDTA disodium salt (10 mg/kg body weight/day for 5 consecutive days) induced no increase in the incidence of post-implantation embryonic deaths, except for a marginal but statistically insignificant increase during wk 2 and 3 of mating.     

Assessment of in vivo mutagenic potency of ethylenediaminetetraacetic acid in albino mice

Ethylenediaminetetraacetic acid (EDTA) disodium salt, a widely used metal chelator, was studied for its potency to induce bone marrow micronuclei, dominant lethal mutations and sperm-head abnormalities in albino mice. The acute oral LD₅₀ dose computed by probit regression was 30 mg/kg body weight in the strain used. Preliminary studies showed that oral administration of EDTA disodium salt at doses of 5, 10 and 15 mg/kg body weight/day on 5 consecutive days did not induce any obvious signs of toxicity. In the bone marrow micronucleus assay acute doses of EDTA disodium salt (5–20 mg/kg body weight) induced a dose-dependent increase in the incidence of micronucleated polychromatic erythrocytes at a 24-hr sampling. However, administration at doses of 5, 10 and 15 mg/kg for 5 consecutive days did not produce any observable effect on either the testicular or epididymal weights and histology. No appreciable alterations were observed in the caudal sperm counts at any of the sampling intervals and there was no treatment-related increase in the incidence of sperm-head abnormalities. Furthermore, treatment of male mice with EDTA disodium salt (10 mg/kg body weight/day for 5 consecutive days) induced no increase in the incidence of post-implantation embryonic deaths, except for a marginal but statistically insignificant increase during wk 2 and 3 of mating.     

Cytogenetic effects of amitriptyline hydrochloride in somatic and germ cells of mice

Amitriptyline hydrochloride, an antidepressant drug, was tested in mice for mutagenic effects in the somatic cells by the micronucleus test and in the germ cells by the air drying technique of Evans et al. Mice were treated orally with the drug at a dose of 70, 140 and 210 mg/kg body weight. The results indicate that the drug is capable of inducing mutations both in the mitotic and meiotic cells of mice.