The Safety of Viscum Album L. in A Murine Model: A Reproductive Toxicity Study

Background: The use of antineoplasic drugs in pregnancy poses a huge safety challenge because of the risk of teratogenicity, mutagenicity and carcinogenicity. The rational use of the herbal medicine Viscum album (VA) has shown promising results in several tumor lines as part of the strategy of immunotherapy and anti-angiogenesis in integrative oncology. The safety of intrauterine fetal exposure to VA is however unknown and can be further evidenced for therapeutic doses in pregnant cancer patients.Methods: 47 pregnant Wistar rats and 399 fetuses bred following exposure to VA were investigated. The rats were randomized into five groups. Control group (CG) received no treatment and stress group (SG) received daily vehicle subcutaneous injections alone in same volume as the treatment groups from day zero until the twentieth day of pregnancy. There were three treatments groups: therapeutic dose group (TG) received the usual therapeutic dose (UTD) of 0.013 mg/kg BW; high dose group (HG) received 12.5 mg/kg BW and very high dose group (VHG) received 25mg/kg BW, daily.Results: Weight gain was greater in the rats, placentas and fetuses in the TG and HG compared to SG. Histology of the placentas showed a greater inflammatory process in HG and VHG.Conclusion: Since no cases of abortion, embryotoxicity, natimortality or teratogenicity were found in the fetuses and histology detected no lesions in the tissues evaluated, it is reasonable to conclude that this drug is safe for use in pregnant rats.

Radioprotective Effects of Zinc and Selenium on Mice Spermatogenesis

Background: Spermatogenesis system is one of the most radiosensitive organs in the body. A usual therapeutic dose of radiation such as the conventional 2 Gy in each fraction of radiotherapy and lower doses seen in diagnostic radiology or a radiation disaster affect the process of spermatogenesis potently. Selenium and zinc are two important elements playing key roles in the development of sperms and also have radioprotective effects. In this study aims to evaluate the radioprotective effect of zinc and selenium against radiation-induced mice testis injury.Materials and Methods: 30 mice were divided equally into 6 groups, including control selenium treated, zinc treated, radiation, radiation + selenium, radiation + zinc. Treatments started from 2 days before irradiation with 2 Gy cobalt-60 gamma rays. After 37 days, all mice were killed for histopathological evaluations.Results: Results showed that exposure to radiation caused a potent effect on spermatogenesis system. Treatment with selenium reversed these radiation effects potently, while zinc had some limited protective effects. Zinc treatment itself caused a detrimental effect on epididymis and, in combination with radiation, it leads to more damage to seminiferous tubules.Conclusion: In contrast to previous studies that proposed zinc to protect spermatogenesis against various toxic agents, results of this study showed that although zinc may protect from some parameters, it potentiates radiation damage on seminiferous tubules and has a detrimental effect on the epididymis. By contrast, zinc and selenium could alleviate radiation-induced toxicity on the most of the evaluated parameters.

Phenothiazine-Induced Sleep Apneas in Normal Infants

A relationship between sudden infant death syndrome and the use of phenothiazine-containing medications is suspected. In order to investigate the influence of phenothiazines upon cardiorespiratory and sleep characteristics, four normal infants (mean age 15.8 weeks) had polygraphic recordings made for one night. The recordings were repeated three nights later, after the daily administration of a usual therapeutic dose of a standard phenothiazine syrup (promethazine, 1 mg/kg of body weight per day). The infants were monitored for six days after the first treatment. Findings from the first polygraphic recordings were normal for each infant. The second recordings disclosed an increase in sleep time, a reduction in the number and duration of awakenings, an increase in non-rapid eye movement (NREM) III sleep state, and a reduction in body movements. During the second night, each infant showed an increase in the number of central apneas, and each infant also had several episodes of obstructive apneas (median duration four seconds). It is concluded that promethazine depresses the arousal and respiratory mechanisms in normal infants during sleep. This observation reinforces the opinion that CNS depressants should be avoided in infants less than 1 year of age; CNS depressants could result in sudden death in apnea-prone infants.

Lettrt To The Editor

Dr. Schwartz's comments are appreciated. It is certainly true that the diphenylhydantoin dosage of 10 mg/kg appears to be excessive with the usual therapeutic dose being 5 to 8 mg/kg of body weight. However, this dosage was not infrequently necessary to obtain seizure control and the blood level in this most difficult group of children with psychomotor seizures often did not exceed the desired therapeutic range of 10 to 20µg/100 ml. It is recommended that initially the lower dosage be used and if seizure control is not attained that the higher dosage be evaluated.

THE ACUTE ORAL TOXICITY OF SPIRAMYCIN

Spiramycin was administered as a suspension by stomach tube in a range of doses to 46 young male albino rats, with 16 controls, and to 14 small mongrel bitches, with eight controls. The oral acute LD50 was found to be 9.4 ± 0.8 g. (mean ± S.D.) per kg. body weight in rats and 5.2 ± 1.6 g. per kg. body weight in dogs. From these values, the oral acute LD50 in man was estimated to be of the order of 1 to 2 g. per kg. body weight or 20 to 40 times the usual therapeutic dose. The clinical effects of these acutely toxic oral doses in rats and dogs were anorexia, vomiting (dogs only), diarrhea, and lassitude, progressing to prostration, pallor, a fall in body temperature, cessation of respiration, and death usually within 48 hours. At autopsy the stomach and intestines were distended with gas and liquid, the tunica propria and submucosa were acutely congested, and there was excessive necrosis and desquamation of the surface epithelium. Areas of acute necrosis were found in the hepatic cells and sinusoids of the liver, and in the (mostly distal) convoluted tubules of the kidney. The cause of death, therefore, was an acute fulminating gastroenteritis accompanied by acute regional necrosis of the liver and kidneys, produced by the orally administered lethal dose of spiramycin.

THE ACUTE ORAL TOXICITY OF SPIRAMYCIN

Spiramycin was administered as a suspension by stomach tube in a range of doses to 46 young male albino rats, with 16 controls, and to 14 small mongrel bitches, with eight controls. The oral acute LD50 was found to be 9.4 ± 0.8 g. (mean ± S.D.) per kg. body weight in rats and 5.2 ± 1.6 g. per kg. body weight in dogs. From these values, the oral acute LD50 in man was estimated to be of the order of 1 to 2 g. per kg. body weight or 20 to 40 times the usual therapeutic dose. The clinical effects of these acutely toxic oral doses in rats and dogs were anorexia, vomiting (dogs only), diarrhea, and lassitude, progressing to prostration, pallor, a fall in body temperature, cessation of respiration, and death usually within 48 hours. At autopsy the stomach and intestines were distended with gas and liquid, the tunica propria and submucosa were acutely congested, and there was excessive necrosis and desquamation of the surface epithelium. Areas of acute necrosis were found in the hepatic cells and sinusoids of the liver, and in the (mostly distal) convoluted tubules of the kidney. The cause of death, therefore, was an acute fulminating gastroenteritis accompanied by acute regional necrosis of the liver and kidneys, produced by the orally administered lethal dose of spiramycin.