Chronic toxicity and carcinogenicity of paclobutrazol in SD rats / 中国职业医学

OBJECTIVE: To explore the chronic toxicity and carcinogenicity of paclobutrazol in SD rats. METHODS: Specific pathogen free SD rats at the age of weaning were randomly divided into control group and low-,medium-,and high-dose groups according the body weight,with 120 rats in each group,half male and half female. The study of combined chronic toxicity and carcinogenicity test in rats was carried out in 2 years by feeding the rats with paclobutrazol. The doses in the 4 groups were 0. 0,11. 7,48. 5 and 193. 9 mg·kg~(-1)·d~(-1) for female rats and 0. 0,13. 5,54. 2 and 241. 9 mg·kg~(-1)·d~(-1) for male rats. The body weight of rats was weighted during the experiment. The blood routine,blood biochemistry,organ coefficient and histopathology examinations were performed at the end of paclobutrazol exposure. The mortality and tumor incidence in rats were calculated. RESULTS: The decrease of body weights in female and male rats in dose groups was observed at 1-2 weeks after the experiment,compared with the same sex control group at the same time point( P < 0. 05).At the end of the exposure,the body weights of female and male rats in all three dose groups were lower than that in the same sex rats of control group( P < 0. 05). The mortality rates of female and male rats in the four groups were not significantly different( P > 0. 05). The brain organ coefficients of female rats in the three dose groups were higher than those female rats in the control group( P < 0. 05). The organ coefficients of liver,kidney and ovary of female rats in highdose group were higher than that of female rats in control group( P < 0. 05). The level of total bilirubin in male rats in the three dose groups was lower than that in control group( P < 0. 05). The organ coefficients of brain and lung in male rats in the medium-and high-dose groups were higher than that in the control group( P < 0. 05). The liver organ coefficient in male rats in the high-dose group was higher than that in the control group( P < 0. 05). A total of 244 rats had 402 spontaneous tumors with a tumor incidence rate of 50. 8%(244/480). The incidence of tumor in control,low-,mediumand high-dose groups were 61. 7%( 74/120), 42. 5%( 51/120), 50. 0%( 60/120) and 49. 2%( 59/120)respectively. There was no statistical significance in the incidence of tumors in three dose groups compared with that of the control group. CONCLUSION: Under the dose conditions designed in this study,the lowest observed adverse effect level of paclobutrazol were 11. 7 and 13. 5 mg · kg~(-1)· d~(-1) in females and males respectively. Paclobutrazol was not found carcinogenic to SD rats.

Efficacy of Zinc Supplementation as an Adjunct to Anti Tubercular Drug Therapy.

Zinc being a stronger electron acceptor than iron might replace iron from the critical thiol groups. So, Zinc supplementation in Tubercular Subjects might help the decompartmentalised state of iron in the body to revert back to normal compartmentalized state of iron. Again, Zinc inhibits the formation of superoxide radicals. Thus, Zinc supplementation might decrease the excess superoxide with simultaneous decrease in the formation of soluble oxygen made by dismutation reaction by the iron cofactored superoxide dismutase secreted extracellularly by the pathogenic M. tuberculosis. The study shows early and effective recovery with Zinc supplementation (50mgm. of elemental zinc orally / day for one month) along with anti - Tubercular drug therapy. This gets support by the significant changes in the serum level of three enzymes – Glutamine Synthetase, Superoxide Dismutase and Cholienesterase. Again, the dose of zinc supplementation instituted with a great benefit and without any toxic symptoms and signs, is below the Lowest Observed Adverse Effect Level (LOAEL) based on the superoxide dismutase activity in erythrocytes with zinc intake.