maneb and Inflammation

Parkinson's disease is a progressive neurological disorder associated with selective degeneration of nigrostriatal dopaminergic neurons. It is the most common of the neurodegenerative movement disorders, affecting approximately 1% of the population over age 65. Though the exact cause of the neurodegeneration is unknown, it has been shown that environmental factors can contribute to the onset of Parkinson's disease. Parkinsonian symptoms are seen following exposure to the herbicide paraquat, and the fungicide maneb. Furthermore, evidence clearly shows that neurodegeneration develops in environments where workers are co-exposed to paraquat and maneb. These neurotoxins cause a pesticide-induced loss of dopaminergic neurons, inducing a Parkinsonian phenotype. The specific mechanisms by which these environmental neurotoxins affect the nigral dopaminergic neurons are unknown. This gap in mechanistic understanding raises a need for further examination of their cytotoxic effects. Despite advances in pharmacotherapy that have improved quality of life, the mortality rate among Parkinson's disease sufferers remains largely unchanged. There is need for a proactive treatment strategy that could provide neuroprotection or neurorestoration. Since evidence has shown that environmental neurotoxins play an important role in nigral degeneration, there is obviously a need to take a closer look at such toxins since a greater understanding could aid in development of novel pharmacological agents with anti-parkinson and neuroprotective effects. In this review, we intend to examine the role of environmental toxins, namely paraquat and maneb, in the neurotoxicity that leads to dopamine depletion.

Topics: Animals; Apoptosis; Drug Interactions; Fungicides, Industrial; Herbicides; Humans; Inflammation; Maneb; Mitochondria; Necrosis; Neurotoxicity Syndromes; Oxidative Stress; Paraquat; Parkinson Disease, Secondary

To evaluate the histopathological, immunohistochemical, and biochemical effects of liver changes after mancozeb administration.. Rats were divided into groups-the control group (n=7) and the mancozeb group (n=7)-, given 500 mg/kg mancozeb dissolved in corn oil daily for four weeks by an orogastric tube. Caspase-3 and tumor necrosis factor-alpha (TNF-α) primary antibodies were used for immunohistochemical analysis.. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values of the mancozeb group increased significantly than ones of the control group. Venous dilatation, inflammation, hepatocyte degeneration, TNF-α, and caspase-3 expression scores increased significantly in the mancozeb group. In the mancozeb group, intensive caspase-3 expression was observed in hepatocyte cells around the central vein in the center of the liver lobule, and there was an increase in TNF-α expression in the inflammatory cells around the enlarged central vein and Kupffer cells and apoptotic hepatocyte cells.. Subacute mancozeb exposure in rats leads to elevated toxicity with impaired liver function, increased inflammation in tissue and increased apoptosis due to cellular damage in the liver, and decreased liver regeneration ability due to congestion and degeneration of blood vessels.

Topics: Alanine Transaminase; Animals; Apoptosis; Aspartate Aminotransferases; Caspase 3; Fungicides, Industrial; Inflammation; Liver; Liver Diseases; Maneb; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Zineb

To determine the immunohistochemical and histopathological changes in facial skin after exposure to maneb (manganese ethylene bisdithiocarbamate), a fungicidal dithiocarbamate pesticide.. In the experimental group maneb was administered by inhalation to 10 male Wistar albino rats for 5 days each week for 3 weeks. As a biological control, the control group (n = 10) received distilled water by spray for the same time period. The experiment was terminated after 3 weeks. Sections of rat facial skin were examined histopathologically.. In the experimental group, microscopic examination of facial skin revealed degeneration of the epidermis, detection of mild inflammatory reaction, and vascular dilation in the connective tissue. Hair follicles and degenerative changes were observed in the deeper parts. In the experimental group, dilation of the blood vessels in the dermis and hemorrhage were supported by an increase in CD34 expression. In addition, a reduction in the number of melanocytes (hypopigmentation) was observed in the hair follicles and epidermis, along with a decrease in the expression of CD117.. Epidermal degeneration, intradermal cell infiltration, vascular changes, and reduction in the number of melanocytes in the follicle and content of cytokeratin in both the epidermis and hair follicle keratinocytes were detected after maneb application. These findings may have important implications in the association with main signaling pathways, including keratinocyte proliferation and differentiation. Disruption of these pathways may cause some dermatoses.

Topics: Animals; Antigens, CD34; Blood Vessels; Epidermis; Gene Expression Regulation; Inflammation; Male; Maneb; Melanocytes; Proto-Oncogene Proteins c-kit; Rats; Skin

Parkinson's disease (PD) is the second most unconcealed neurodegenerative disorder labelled with motor impairments. Two pesticides, manganese ethylene-1,2-bisdithiocarbamate (maneb) and 1,1'-dimethyl-4,4'-bipyridinium dichloride (paraquat), together, are reported to increase the incidence of PD in humans and Parkinsonism in mice. Conversely, silymarin and melatonin, two naturally occurring antioxidants, rescue from maneb- and paraquat-induced Parkinsonism. The study examined silymarin- and melatonin-mediated changes in the expression of selected genes in maneb- and paraquat-induced Parkinsonism employing mouse discover chips microarrays. The mice were treated intraperitoneally (i.p.), daily, with silymarin (40 mg/kg) or melatonin (30 mg/kg) for 9 weeks along with vehicles. Subsets of animals were also treated with maneb (30 mg/kg; i.p.) and paraquat (10 mg/kg; i.p.), twice a week, for 9 weeks. Whilst the expression of genes in the striatum was determined by microarray, the expression of randomly selected transcripts was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Combined maneb- and paraquat-treatment altered the expression of several genes associated with apoptosis, inflammation, cell cycle, cell-signalling, etc. pathways. Silymarin and melatonin significantly resisted the changes in the expression of a few genes related to apoptosis, inflammation, cell cycle, cell-signalling, etc. The expression patterns of seven randomly selected genes were analyzed by qRT-PCR, which were found to follow the similar trends, as observed with microarray. The results obtained from the study thus demonstrate that despite resemblances, silymarin and melatonin differentially offset maneb- and paraquat-induced changes in transcriptome.

Topics: Animals; Antioxidants; Apoptosis; Cell Cycle; Disease Models, Animal; Gene Expression Regulation; Inflammation; Ion Channels; Male; Maneb; Melatonin; Mice; Mitochondria; Oxidative Stress; Paraquat; Parkinsonian Disorders; Pesticides; Signal Transduction; Silymarin