Allatostatin-like immunoreactivity in the optic lobe of the fly Sarcophaga bullata.

An antiserum against Diploptera allastostain 1 (Dip-AST1) was used to map the distribution of allatostain containing neurons in the optic lobes of the fly Saccrophaga bullata. Strongly immunoreacting neurons were found in two areas of the optic ganglia, namely, the medulla and the area between medulla and lobula. These cells were generally interneurons arborizing the base of the medulla. The positive reaction of specific populations of the optic lobe neurons against allatostain antiserum suggests some role for this neuropeptide in the visual physiology of the fly.

Restoration of methylmercury inhibited adenosine triphosphatases during vitamin and monothiol therapy.

The aim of our investigation was to examine the efficacy of monothiols and vitamins in the restoration of ion-dependent ATPases in mice intoxicated with methylmercury chloride (MMC). A daily dose of glutathione (GSH), N-acetyl-DL-homocysteine thiolactone (NAHT), vitamin B complex, or vitamin E, either alone or in combination, resulted in significant recovery of N+, K+, Mg++ ATPases. A significant recovery was noted in some therapeutic groups. As the therapeutic agents used in this study are natural physiological components present in all the animals, they are unlikely to be injurious if applied in appropriate doses. Hence, they can be safely recommended for methylmercury detoxication.

Monothiols and Vitamins are Ideal Therapeutic Agents for Mercury Elimination from Nervous and Non-Nervous Tissues of Fish.

Use of mercury and its compounds in various industries and agriculture is increasing its concentration in aquatic environment and affecting the organisms living therein. Among these, the fishes are commercially important for humans as an important source of protein. The fish meat transfers good amount of mercury to man, therefore, its elimination is quit essential both from fishes and the consumers. As a step in this direction, the present study has been designed to detoxify the fishes from mercury. For this purpose a freshwater fish (Channa punctatus) was treated with mercuric chloride (0.5 ppm) for 96 h and thereafter, detoxicated with vitamin B complex, glutathione and N-acetyl-DL-homocysteine thiolactone used either alone or in various combinations for another 96 h. One group of 96-h mercury treated animals were kept in tap water and sacrificed after 192 h. This group was considered as mercury washed group and it served as control to all therapeutic groups. Mercury treated fish showed a highest concentration of the metal in kidney followed by liver, gills, brain and muscles. In mercury washed group, metal was removed significantly from all the non-nervous tissues, but in brain about 52% further increase was observed. The results obtained from theraputic studies were quite exciting as 50-80% mercury was mobilized from all tissues including brain within 96 h of treatment.

Vitamins and monothiols efficacy in the restoration of adenosine nucleotide degradation enzymes altered during methylmercury intoxication.

Male albino mice were intoxicated with a daily dose of 1 mg/kg of methylmercury chloride (MMC) for 7 days, and were treated thereafter with glutathione, N-acetyl-DL-homocysteine thiolactone, vitamin B complex, and vitamin E, either alone or in combinations, for the next 7 days. The animals were sacrificed on the eighth day, with the exception of one group that was kept without toxic exposure for an additional 7 days and sacrificed on the fifteenth day. Brain, spinal cord, kidney, and liver of the animals were examined for changes in adenosine deaminase and 5' nucleotidase. We found a severe inhibition of these enzymes during MMC intoxication and significant recovery during monothiols and vitamins administration, indicating the effectiveness of these agents in methylmercury detoxication.

Fluctuation of trace elements during methylmercury toxication and chelation therapy.

The aim of the present investigation was to check the fluctuation in essential elements, such as Na, K, Mg, Mn, Cu, Zn, Cr and Ni in the brain, spinal cord, liver and kidney of mice during methylmercury chloride (MMC) toxication and therapy with monothiols (N-acetyl-DL-homocysteine thiolactone and glutathione) and vitamins (vitamin B complex and E). Mercury deposition and its elimination during chelation therapy were also screened for comparative purposes. The animals were dosed for 7 days with MMC 1 mg/kg/d and some were then kept without treatment for a further. 7 days. Other MMC-treated animals were immediately given one of the above antidotes for 7 days. All the animals were sacrificed on the 15th day. There was a decrease in all elements during MMC toxication with few exceptions, for example, copper was increased in the liver as was sodium in the kidney. Treatment with the thiols and vitamins restored the levels of these elements in certain tissues towards normal, but their concentrations remained abnormal in most instances. The fluctuations in the concentration of these elements were attributed to their association with various macromolecules.

Ameliorative capacities of vitamins and monothiols post therapy in the restoration of methylmercury altered glutathione metabolism.

The recovery of glutathione and its metabolising enzymes (glutathione disulfide reductase, glutathione peroxidase, thiol transferase, gamma-glutamyl transpeptidase and glutathione transferase) along with sulfhydryl groups and byproduct of lipid peroxidation (malondialdehyde) in the brain, spinal cord, kidney and liver of mice, altered during methylmercury chloride (MMC) intoxication, is recorded in post-therapeutic treatment with vitamins and monothiols. For this purpose ten groups of animals were intoxicated with 1 mg/kg MMC/day for 7 days. Out of these, one group was sacrificed on 8th day and one group was kept without toxicant for another seven days before sacrificing on 15th day. Study shows significant decrease of various biomolecules of glutathione metabolism during MMC application, which are further decreased with increasing the duration on 15th day. The trend is same in all the tissues with few exceptions. However, malondialdehyde, a byproduct of lipid peroxidation, is increased with increasing the duration after intoxication. Study also shows a significant recovery (in many cases a complete control level) of most of the components with one or the other chelator or with their combined therapy. Therefore, it is concluded from overall study that vitamins B complex and E, GSH (or its precursor NAHT) either alone or in combinations, are quite suitable for methylmercury post-therapy.

Acetylcholinesterase fluctuations in central nervous system of rat during methylmercury intoxication and chelation therapy.

A daily dose of 1 mg/kg and 10 mg/kg of methylmercury chloride (MMC) was injected to separate sets of rats for 2 days, 7 days, and 15 days. Low and high doses of four MMC antagonists, namely N-acetyl-DL-homocysteine thiolactone (NAHT), glutathione (GSH), D-penicillamine (DPA), and sodium selenite (SEL) were injected intramuscularly (i.m.) to MMC-treated animals after an interval of half an hour. The animals were sacrificed on the 3rd, 8th, and 16th day, respectively. An additional group of rats was treated with MMC for 7 days; thereafter, it was kept free of toxic exposure for 7 days and sacrificed on the 15th day. The brain was dissected and separated into olfactory bulbs, cerebral hemispheres, cerebellum, and medulla oblongata. Each part of the central nervous system (CNS) was studied separately. We found a dose- and duration-related acetylcholinesterase (AChE) inhibition in all CNS areas. The use of antagonists showed different effects in different CNS areas, but no appreciable recovery of AChE activity could be obtained with the doses used.

Ameliorative capacities of vitamins and monothiols administered alone or in combinations in methylmercury mobilisation in nervous and non-nervous tissues of mice.

The extent of mercury mobilisation was recorded from various tissues (brain, spinal cord, liver and kidney) of male mice administered with a daily dose of methylmercury chloride (1 mg/kg) for seven days. For this purpose 10 groups of animals were intoxicated. Out of these, one group was sacrificed on 8th day and one group was kept without toxicant for another seven days before sacrificing on 15th day. To the rest of the groups were given a daily dose of N-acetyl-DL-homocysteine thiolactone (NAHT), glutathione (GSH), vitamin B Complex and E, applied either alone or in combinations. All these animals were sacrificed on the 15th day. The mercury clearance rate during thiols, vitamins and their co-administration was examined. Study shows that both the vitamins were able to increase mercury elimination from the nervous and non-nervous tissues. Their combination with NAHT was not suitable as mercury level was increased in all the tissues except kidney as compared to NAHT alone treated group. However, vitamin B Complex combination with glutathione was much advantageous. It is concluded from the overall study that application of vitamin B Complex and E either alone or in combination with GSH is quite suitable for methylmercury post-therapy.

Inefficiency of metal chelators to promote recovery of methylmercury inhibited CNS succinic dehydrogenase.

This paper deals with the level of succinic dehydrogenase (SDH) in various locations of the central nervous system (CNS) of rat, treated with methylmercury chloride (MMC) and later with antagonists. None of the CNS areas reveals any effect after 2 days of MMC application, but further treatment causes a linear inhibition of the enzyme with increasing duration of MMC exposure. Maximal inhibition in all regions is exhibited after 15 days of treatment. In absolute terms, the maximal inhibition is observed in the olfactory bulbs and the minimal effect is seen in the spinal cord after 15 days with low and high doses of MMC respectively.

Therapeutic abilities of thiol compounds in the restoration of methylmercury-inhibited cholesterol and triglycerides of the rat's central nervous system.

The present study was basically designed to gain an insight into the alterations in the levels of cholesterol and triglycerides in various neuroanatomical areas of the rat under the influence of different doses and durations of methylmercury chloride (MMC), N-acetyl-DL-homocysteine thiolactone (NAHT), and glutathione (GSH) applications. The study showed insignificant alterations in the levels of both the metabolites after two days of drug and antagonist application. The rest of the animal groups exhibited a progressive inhibition of both the metabolites in all the CNS areas with increasing dose and duration of drug treatment. The antagonists, NAHT and GSH, were able to cause a recovery in both the metabolites in most of the groups, yet in no case were absolute control values achieved. It was concluded that antagonists alone are not helpful in mobilizing the mercury as well as producing a recovery in the biochemical lesions induced in the CNS.

Inability of thiol compounds to restore CNS arylsulfatases inhibited by methyl mercury.

Arylsulfatase A and B activities have been analysed in different areas of the CNS (olfactory bulbs, cerebral hemispheres, cerebellum, medulla oblongata and spinal cord) during methyl mercuric chloride (MMC), N-acetyl-DL-homocysteine thiolactone (NAHT) and glutathione (GSH) treatment. Male albino rats were administered with two different doses of MMC (1 mg/kg and 10 mg/kg), NAHT (40 mg/kg and 80 mg/kg) and GSH (100 mg/kg and 150 mg/kg) for 2, 7 and 15 days, and sacrificed on the 3rd, 8th and 16th day, respectively. Likewise, eight groups of animals, after treatment for 7 days with MMC, were kept for another 7 days and sacrificed on the 15th day (normal withdrawal). Sixteen groups of 7 days MMC pretreated animals were given either NAHT or GSH for another seven days before sacrifice on the 15th day. The study revealed 1) a dose and duration dependent inhibition of the enzymes in all CNS areas, 2) a maximum inhibition of the enzymes among various hydrolases reported so far, and 3) none of the antagonists restored the enzymes significantly except for one group with NAHT. It is, therefore, concluded that arylsulfatases are more sensitive to MMC than other lysosomal enzymes, and the antagonists used here have not helped their restoration.

Differential distribution of immunoreactive angiotensinogen in the hind-brain and spinal cord of neonatal and adult rats.

The present communication deals with the cytochemical localization of angiotensinogen (ATG) immunoactivity in the hind-brain and spinal cord of neonatal (1-day-old) and adult (3-month-old pregnant) female rats. In the neonatal hind-brain, the immunoreactive cells were more numerous than in that of adult rats. In the adult rat hind-brain, the number of ATG-positive cells was quite limited in each nucleus. Further, in some nuclei, only neurons or neuroglia were positive, while in others the immunoactivity was observed in both the components. Spinal cords of neonatal rats showed a few undifferentiated ATG-positive cells in the grey matter. Contrary to this, the spinal cord of adult animals contained numerous immunoreactive glial cells in the grey matter, fasciculus cuneatus and fasciculus gracilis. Immunoactivity in the neurons was localized in the Nissl bodies.

Dose and duration related methylmercury deposition, glycosidases inhibition, myelin degeneration and chelation therapy.

Methylmercury accumulation in different parts of the CNS (olfactory bulbs, cerebral hemispheres, cerebellum, medulla oblongata and spinal cord) in relation to the cytoarchitectural changes in myelin sheath as well as in glycosidases levels have been reported. Male albino rats were treated with low and high doses of methylmercury chloride (1 mg/kg and 10 mg/kg) N-acetyl-DL-homocysteine thiolactone (40 mg/kg and 80 mg/kg) and glutathione (100 mg/kg and 150 mg/kg) for varied time periods. The study shows a dose and duration dependent accumulation of mercury in all the CNS areas coinciding with a progressive myelin degeneration and inhibition of the glycosidases. A casual relationship between the amount of mercury accumulation and the extent of enzymes inhibition, in any particular area of CNS, could not be established. Similarly none of the antagonists is (though has been successful in recovering the enzymes and lessening the mercury burden in a few isolated cases) able to bring an absolute control value in any group.

Angiotensinogen in the developing rat fetal hindbrain and spinal cord from 18th to 20th day of gestation: an immunocytochemical study.

We have detected angiotensinogen immunoreactivity in the hindbrain and in the spinal cord of rat fetuses during the 18th to 20th day of gestation. In the 18th-day fetus, a few immunoreactive angiotensinogen cells are localized in precise brain areas. Their number sharply increase during the 19th and 20th day gestation period when there is an active cell differentiation and cell growth. These observations suggest a role of the renin-angiotensinogen system during cell growth and cell differentiation.

A therapeutic profile of metal chelators in the detoxication of methylmercury chloride inhibited acid and alkaline phosphatases in different areas of the central nervous system of rats.

Acid and alkaline phosphatase changes in various parts of the central nervous system (olfactory bulbs, cerebral hemispheres, cerebellum, medulla oblongata, and spinal cord) were analyzed during methylmercury chloride (MMC) treatment with a dose of 5 mg/kg/day body weight. The drug was subcutaneously introduced into the animals and the enzymes were analyzed after 2, 7, and 15 days' treatment. One group of animals was treated for seven days and kept without drug for another seven days (withdrawal group). The antagonizing capacities of four chelators, namely, N-acetyl-DL-homocysteine thiolactone (NAHT), D-penicillamine (DPA), glutathione (GSH), and sodium selenite (SEL), were also analyzed in relation to the restoration of enzymes. Study results show a linear inhibition of acid and alkaline phosphatases with increasing duration of MMC treatment. However, the magnitude of enzymatic inhibition is different in different brain areas. After 15 days' treatment, maximum inhibition of acid and alkaline phosphatases was recorded in the spinal cord and cerebellum, respectively. Chelators also exhibited differential recovery of the enzymes in various animal groups, as well as in discrete brain areas. No uniformity in the recovery of the enzymes with chelators was observed. However, study results show that biochemical parameters are good indicators of early recognition of neurotoxicity.

Co-existence of renin-like immunoreactivity in the rat maternal and fetal neocortex.

Renin-like immunoreactive material was examined in maternal and fetal brain. A continuous layer of renin was localized in neocortex which begins in the fetal brain during gestation and continues throughout the animal's normal life.