Effect of beta-carotene on the inhibition of lung metastasis in mice.

Effect of beta-carotene on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice. Simultaneous administration of the compound after tumor induction produced a significant reduction (71.36%) in tumor nodule formation. Increased lung collagen hydroxyproline (22.37 microg/mg protein) in the metastasized lungs of control animals compared to the normal animals (0.95 microg/mg protein) was significantly reduced (4.19 microg/mg protein) in the beta-carotene treated animals. High amount of uronic acid (355.83 microg/100mg tissue ) in the metastasized control animals was significantly reduced (87.87 microg/100 mg tissue) in the animals treated with beta-carotene. Lung hexosamine content also was inhibited significantly in the beta-carotene treated animals (1.58 mg/100 mg lyophilized tissue) compared to the untreated control animals (4.2 mg/100 mg lyophilized tissue). The elevated levels of serum sialic acid and serum gamma glutamyl transpeptidase activity in the untreated control animals was significantly reduced in the animals treated with beta-carotene. Beta carotene treated animals were survived up to 69 days. Histopathology of the lung tissue also correlated with the above parameters and life span of the drug treated animals. Our results reveal the antimetastatic activity of beta-carotene which are abundantly present in green plants, vegetables and fruits.

The embryotoxic and osteolathyrogenic effects of semicarbazide.

The osteolathyrogenic agent semicarbazide was assayed for its toxicity and teratogenicity using early embryos of the frog Xenopus laevis. The 96-h LC50 is 1504.20 mg/l while the 96-h EC50 is 76.28 mg/l. Embryo length is altered prior to the onset of other effects indicated by a reduction in stage of development. The major malformation is associated with the notochord where the notochordal sheath is reduced owing to the disruption in the maturation and/or deposition of the connective tissue fibers.

Collagenase inhibitors: rationale for their use in treating corneal ulceration.

Tissue collagenases have been implicated in corneal ulceration in human corneal disease and in ulceration of the rabbit cornea that has served as a model system. Such enzymes from the rabbit and human cornea are inhibited by metal-binding agents of the EDTA type, by thiols, and by the human serum antiprotease alpha2-macroglobulin. Determination of the relative efficacies of collagenase inhibitors indicates that EDTA and Ca-EDTA are about one hundred times more effective on a molar basis than L-cysteine and its derivatives, N-acetyl-L-cysteine and D-penicillamine. The alpha2-macroglobulin on a molar basis, is superior as an inhibitor to the metal-binding agents and thiols. Although Ca may be a necessary cofactor of the corneal collagenases, such a requirement has not been established unequivocally. Inhibition and isotope studies do indicate a requirement for Zn. Thiols are thought to inhibit corneal collagenases by binding to or removing an intrinsic metal cofactor (Zn), and/or possibly by reducing one or more disulfide bonds. Inhibition by both EDTA-type agents and thiols is largely reversible by dialysis. The human alpha2-macroglobulin appears to inhibit corneal colleagenases irreversibly by forming tight complexes with them. Ca-EDTA, cysteine, and acetylcysteine, given as eyedrops, are able to prevent or retard ulceration in the alkali-burned rabbit cornea. They appear to have some efficacy in the prevention of corneal ulceration in humans. EDTA-type compounds are quite stable under routine storage, while acetylcysteine is more stable than cysteine. EDTA is quite toxic and should not be used as eye medication. Ca-EDTA has a low toxicity, and cysteine and acetylcysteine have even lower toxicity. It is not yet certain which inhibitor has the most favorable therapeutic index for clinical use, or is the optimal mode of drug delivery known. However, the collagenase inhibitors seem to have therapeutic promise in the prevention of corneal ulceration.