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Hexaamminecobalt(III) chloride ([Co(NH3)6]Cl3) was investigated for its antineoplastic role in relation to tumor marker enzymes, drug metabolizing enzymes, oxidative stress-related parameters, and histopathological analysis of liver and lung tissues of mice. Initiation was performed using a single intraperitoneal injection of diethylnitrosamine (DENA) at a carcinogenic dose of 90 mg/kg body weight. The cobalt complex supplementation at a dose of 100 ppm in drinking water was given ad libitum throughout the experimental period of 14 weeks. In comparison to lung, the cobalt complex supplementation was found to reverse DENA-induced biochemical changes more effectively in liver. Histological examination of liver and lung from DENA-initiated and cobalt-complex-supplemented mice showed considerable protection in the case of liver compared to that of lung. The involvement of the [Co(NH3)6]Cl3 in modulating several factors associated with carcinogenesis induced by DENA thus showed its anticarcinogenic potential against chemically induced hepatocarcinogenesis.

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Summary Gossypol acetic acid at the dose of 5 mg/rat/day for 2 and 4 weeks did not cause any significant effect on the body weight, testis, epididymis, seminal vesicle and prostate weight, nor gossypol treatment had any significant effect on the activities of acid phosphatase and succinic dehydrogenase in the testis. Changes in the testis ATPase activity were, however, significant after gossypol treatment. During the course of present investigations no effect of gossypol treatment on 3H thymidine incorporation into DNA of testicular cells was observed, nor there were any changes in the DNA and total protein content of the testis after gossypol treatment. Gossypol treatment did not cause any effect on the plasma Na+ level. However, transient decrease in the plasma K+ level was observed; decrease in K+ level two weeks after gossypol treatment was restored to normal after 4 weeks of gossypol treatment. No changes in the histology of the testis were observed 2 weeks after gossypol treatment but marked inhibition of spermatogenesis was observed 4 weeks after gossypol treatment. Motility of vas deferens spermatozoa was also markedly inhibited 4 weeks after gossypol treatment. In the light of the present observations and those of others, there is a clear demonstration that gossypol acts directly on the spermatozoa and on the testis; at both the sites the drug interferes in the ATPase activity. Untersuchungen über die Antifertilitätssubstanz Gossypol‐Essigsäure. III. Der Einfluß von Gossypol‐Essigsäure auf den Rattenhoden Zusammenfassung Gossypol‐Essigsäure (G) ‐ in einer Dosis von 5 mg/Ratte/Tag für 2 und 4 Wochen appliziert ‐ verursacht keine signifikanten Veränderungen des Körpergewichtes, des Gewichtes der Hoden, Nebenhoden, Samenblasen und Prostata; G‐Behandlung hat auch keinen Einfluß auf die Aktivität der sauren Phosphatase und der Succinatdehydrogenase des Hodens. Demgegenüber konnte eine Änderung der ATPase‐Aktivität nach G. festgestellt werden. Im Verlauf der gegenwärtigen Untersuchungen ließ sich kein Einfluß von G auf den 3H‐Thymidin‐Einbau in DNA von Hodenzellen beobachten. Auch ergaben sich keine Veränderungen des Gehaltes an DNA und Total‐Protein des Hodens. Plasma‐Na+ wurde nicht verändert. Ein flüchtiger Abfall des Plasma‐K+ ergab sich innerhalb von 2 Wochen Anwendung, während nach 4 Wochen ein Normalstatus wieder erreicht war. Die Hodenhistologie war erst nach 4 Wochen G‐Therapie deutlich beeinflußt im Sinne einer Spermatogenese‐hemmung. Die Motilität der Spermatozoen aus dem vas deferens war ebenfalls deutlich nach 4 Wochen herabgesetzt. Es wird festgestellt, daß aufgrund der gegenwärtigen Forschungsergebnisse ganz klar der Nachweis geführt werden kann, wonach Gossypol direkt die Spermatozoen beeinflußt und wonach Gossypol die ATPase‐Aktivität störend beeinflußt.

Zusammenfassung Untersuchungen über das Antifertilitätsmittel Gossypol‐Essigsäure. II. Der Effekt von Gossypolacetylsäure auf die Motilität und ATPase‐Aktivität menschlicher Spermatozoen Es wurde eine deutliche Reduktion der Motilität menschlicher Spermatozoen beobachtet, die unterschiedlich lange mit 10 und 100 μg Gossypol‐Essigsäure bei 37° C inkubiert wurden. Die Motilität war nach 210 Minuten von 83% auf 4% reduziert (p < 0,001). Es wurde eine signifikante Abnahme der Aktivität der Ca++ und Mg++ aktivierten ATPase nach Gossypol‐Behandlung beobachtet (p < 0,005). Die Veränderungen der Zink++ Konzentration in den Spermatozoen nach Gossypol‐Behandlung waren jedoch nicht signifikant. Die vorliegende Untersuchungen legen den Schluß nahe, daß die Abnahme der Spermatozoenbeweglichkeit nach Gossypol‐Behandlung auf der Beeinträchtigung der ATPase‐Aktivität in den Spermatozoen beruht.

The feasibility of using a vaccine against luteinizing-hormone-releasing factor for suppression of pituitary and gonadal functions has been indicated for some time. Antibody production against this low-molecular-weight, naturally occurring decapeptide, however, requires to be coupled to a carrier protein to enhance its immunogenicity. LHRH was coupled to diphtheria toxoid (DT). Adult male Sprague-Dawley rats with a mean basal body weight of 200 g were immunized with anti-LHRH-DT (20 micrograms/injection/rat) at four-week intervals. An equal number of unexposed animals served as controls. Six animals were killed every two weeks up the end of the week 43. The vaccination schedule did not have any effect on the gain in body weight, nor was any adverse effect of vaccination observed in the course of the investigations. The pituitary, prostate, epididymis, testes, seminal vesicles, adrenal and thyroid were excised for determination of organ weight and histological examination. The adrenal, pituitary and thyroid showed no remarkable weight changes during the observation period, whereas the weights of the reproductive organs demonstrated significant reductions compared to those of the control group. The histopathology revealed marked to significant changes in the gonads and the accessory sex organs including the prostate. A progressive phase of regeneration of spermatogenesis was evident 98 days after vaccination. Total recovery of spermatogenesis was observed 300 days after vaccination. The mating studies showed the return of fertility 300 days after vaccination. The litters borne were normal. Prostate showed recovery after 154 days of vaccination. Our observations lend strong support to the hypothesis that anti-LHRH vaccine can be effectively used on the management of prostate carcinoma. If the vaccination is given together with a suitable dose of long-acting androgen, contained in an adequate delivery system, the regimen may be used for the regulation of male fertility.

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Studies were carried out to determine the antifertility and reversibility effect of pyrimethamine (PYR) in adult male mice. The parameters mainly included sperm count and motility, fertility, histoarchitecture of testis and testicular cell kinetics quantitatively following oral administration of PYR (50 mg/kg body weight per day) for 30 days. The same parameters were also studied in PYR-treated animals which were allowed to recover for 45 days (recovery group). The results suggest that sperm motility as well as counts were significantly decreased in PYR-treated animals, and the fertility rate fell to zero. Testicular histology as well as germ cell kinetics were altered. However, in the animals of the recovery group, all the parameters studied were more or less similar to those of control animals. The study demonstrates the antifertility as well as reversible efficacy of PYR.