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1.
Metab Brain Dis ; 37(2): 343-357, 2022 02.
Article in English | MEDLINE | ID: mdl-35048324

ABSTRACT

Alzheimer's disease (AD) is a progressive neurodegenerative disease that afflicts millions of people all over the world. Intracerebroventricular (ICV) injection of a sub-diabetogenic dose of streptozotocin (STZ) was established as an experimental animal model of AD. The present study was conducted to evaluate the efficacy of curcumin nanoparticles (CNs) against the behavioral, neurochemical and histopathological alterations induced by ICV-STZ. The animals were divided into: control animals, the animal model of AD that received a single bilateral ICV microinjection of STZ, and the animals protected by a daily oral administration of CNs for 6 days before the ICV-STZ injection. The animals of all groups were subjected to surgical operation on the 7th day of administration. Then the administration of distilled water or CNs was continued for 8 days. The ICV-STZ microinjection produced cognitive impairment as evident from the behavioral Morris water maze (MWM) test and induced oxidative stress in the cortex and hippocampus as indicated by the significant increases in lipid peroxidation and nitric oxide (NO) levels and the significant decrease in reduced glutathione (GSH) levels. It also produced a significant increase in acetylcholinesterase (AChE) and tumor necrosis-alpha (TNF-ɑ) and a significant decrease in Na+,K + -ATPase. In addition, a significant increase in amino acid neurotransmitters occurred in the hippocampus, whereas a significant decrease was obtained in the cortex of STZ-induced AD rats. CNs ameliorated the behavioral, immunohistochemical and most of the neurochemical alterations induced by STZ in the hippocampus and cortex. It may be concluded that CNs might be considered as a promising therapeutic agent for the treatment of AD.


Subject(s)
Alzheimer Disease , Curcumin , Nanoparticles , Neurodegenerative Diseases , Acetylcholinesterase/metabolism , Alzheimer Disease/chemically induced , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Animals , Curcumin/pharmacology , Curcumin/therapeutic use , Disease Models, Animal , Humans , Male , Maze Learning , Oxidative Stress , Rats , Rats, Wistar , Streptozocin/toxicity
2.
Toxicol Rep ; 5: 1069-1077, 2018.
Article in English | MEDLINE | ID: mdl-30425928

ABSTRACT

OBJECTIVE: Heavy metals are major elements polluting our universe. The inhalation, ingestion or even contacting human body with these elements results in huge health problems. The most common pollutant in our surrounding is mercury. Therefore, the present study aimed to elucidating the protective ability of hot water extracts of dandelion (DA), coriander (CO), date palm seeds (DS), probiotic supernatant (PS) and their combined mixture against mercury-induced neurotoxicity and altered testosterone levels in male rats. METHODS: Fifty six male rats were randomly allotted into seven groups (n = 8 rats/group). Group1 (negative control; NC) animals were fed on the basal diet only, group2 (positive controls; PC) animals were fed on the basal diet and given an aqueous solution of mercuric chloride (25 ppm mercuric) in drinking water. Animals of the antioxidant-treated groups (3-7) were fed on the basal diet and given an aqueous solution of mercuric chloride (25 ppm mercuric) in drinking water together with the herbal antioxidant extracts and probiotics (25 ml/rat/day) throughout the experimental period. Where, group3 (Hg/CO) given coriander extract, group4 (Hg/DA) given dandelion extract, group5 (Hg/DS) given date palm seeds extract, group6 (Hg/PS) given probiotic supernatant, and group7 (Hg/Mix) given mixture of equal quantities of probiotic supernatant together with the three herbal extracts. The treatment lasted for 6 weeks, animals were sacrificed and blood samples were collected. Blood testosterone, enzyme activity and histopathological sections were performed. RESULTS: The obtained data exhibited that mercury intoxication revealed increases of lactic dehydrogenase and decreases of glutathione-s-transferase and testosterone. Light microscopic investigations of the brain cortex and cerebellum were suggestive of multiple foci of inflammation, cellular infiltration, gliosis and degeneration. Moreover, decreased glial fibrillary acidic protein (GFAP)-immunoreactivity and potential astrocyte toxicity both reflected impaired neuro-protective function of astrocytes necessary for maintaining the brain structure and function. CONCLUSION: Administration of the herbal extracts and their mixture with probiotics enhance the body defense and contain protective factor against mercury neurotoxicity and for maintaining normal testosterone levels in male rats. Also, treatment restored the normal control levels of biochemical attributes and histological architecture.

3.
Med Sci Monit ; 13(3): BR73-83, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17325631

ABSTRACT

BACKGROUND: Gentamicin (GM) is an antibiotic whose clinical use is limited by its nephrotoxicity. Thus the present study was undertaken to investigate if carnosine, an antioxidant, could protect the kidney in this experimental model. MATERIAL/METHODS: The animals were divided into seven groups each of 10 animals: one control group, two healthy carnosine groups (10 mg/kg/day), two GM groups (80 mg/kg/day), and two carnosine-GM groups. Kidney function tests, histopathological, ultrastructural, and enzymatic histochemical studies clarified GM nephrotoxicity. RESULTS: GM rat showed early kidney function failure as blood creatinine and blood urea were significantly increased after one and two weeks. Experimental evidence suggested a role of reactive oxygen species in GM-induced nephrotoxicity. Histopathological examination revealed degenerative changes in glomeruli and tubules. Ultrastructural study showed glomerular changes, some degeneration of both distal and collecting tubules. The proximal tubules showed marked degrees of changes and necrosis. Enzymatic histochemical studies of GM rats revealed marked elevation of lactate dehydrogenase (LDH) and inhibition of succinic dehydrogenase (SDH), alkaline phosphatases (ALP), acid phosphatases (ACP), and adenosine triphosphatase (ATPase). Blood creatinine and urea were normalized in the carnosine-GM group after one and two weeks. Structural and enzymatic histochemical pictures were greatly ameliorated. CONCLUSIONS: The mechanism by which carnosine has a protective effect on GM-induced nephrotoxicity was attributed to its many actions: double antioxidant action, protein molecule protection, removal of harmfully modified ones, activation of immune system, preservation of membrane fluidity, and cytosolic buffering. Carnosine thus offers a promise of ameliorating GM nephrotoxicity.


Subject(s)
Carnosine/pharmacology , Gentamicins/toxicity , Kidney Diseases/pathology , Animals , Enzymes/metabolism , Kidney Diseases/chemically induced , Kidney Diseases/enzymology , Kidney Diseases/physiopathology , Kidney Function Tests , Kidney Glomerulus/drug effects , Kidney Glomerulus/pathology , Kidney Glomerulus/physiopathology , Kidney Glomerulus/ultrastructure , Male , Rats
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