No abstract

The function of neuromelanin is not known, but some properties of the pigment suggest a protective action. Its unique ability to accumulate and retain several compounds, such as various amines and a number of metals, may protect the pigment-containing neurons from high exposure to harmful substances. This possible mechanism of protection may however in certain instances be of a double-edged nature, as accumulation of neurotoxic agents with a high melanin affinity may cause toxic concentrations in the neuro-melanin-containing cells. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) seems to be such a compound, as it has been found to preferentially destroy neuromelanin-containing cells. The degree of MPTP neurotoxicity seems to be related to the amount of neuromelanin present in the particular species. It is possible that also manganese, which is known to cause an extrapyramidal disorder resembling Parkinson's disease, causes injury to neuromelanin-bearing neurons due to its melanin affinity. This mechanism may be involved in other forms of chemically induced Parkinsonism and possibly also in idiopathic Parkinson's disease, although the offending agent remains to be discovered.

A carcinogenicity study was conducted by administering a purified senna extract via the drinking water to Sprague-Daw-ley rats of each sex for 2 years. The daily doses received were 0, 5, 15 and 25 mg/kg. Histopathological examination was restricted to tissues from the gastrointestinal tract, liver, kidneys, adrenals and from tissues with any observed abnormalities or masses. A laxative effect was observed in high-dose females, and in mid- and high-dose males. No significant differences in survival were found between treated and control groups. Mean body weight gain was significantly decreased in high-dose males. Increased kidney weights were noted in mid-dose males and females, and high-dose females. Histopathological examination of control and high-dose rats did not indicate any difference in the incidence of neoplastic lesions. As regards non-neoplastic lesions, a treatment- but not dose-related increase in reactive mesenteric lymph node hyperplasia was observed in preterminally sacrificed rats. However, a corresponding increase was not noted in the terminally sacrificed rats or when preterminal and terminal animals were combined. No ultrastructural changes in the myenteric nerve plexus of the colon and jejunum could be detected in the small number of investigated tissue samples. In conclusion, results from the present investigation do not indicate any relationship between long-term administration of purified senna extract and gastrointestinal, liver, kidney or adrenal tumors in the rat.

No abstract

The distribution of radioactivity in pigmented mice after a single intravenous injection of 1-(3H) methyl-4-phenyl-1,2,3,6-tetrahydropyridine (3H-MPTP) was studied by quantitative whole body autoradiography and liquid scintillation counting. Pretreatment with the monoamine oxidase inhibitors clorgyline, pargyline and deprenyl, or the catecholamine reuptake inhibitor nomifensine was performed 30 min. prior to the 3H-MPTP administration. A high uptake of radioactivity was observed in the striatum, nucleus accumbens, midbrain area and locus coeruleus, and also in the adrenal medulla. This uptake was inhibited by deprenyl or pargyline pretreatment, but not after clorgyline or nomifensine pretreatment. An extensive uptake which was not influenced by deprenyl or pargyline treatment was found in the melanin-containing tissues of the eye. This accumulation is due to the melanin affinity of MPTP and its metabolites. A comparatively rapid elimination from the brain of MPTP and its metabolites was observed, which may be due to the lack of neuromelanin in mice.