Treatment and prophylaxis of ifosfamide-induced encephalopathy with intravenous methylene blue

Sánchez-Muñoz, Alfonso; Tapiador, A. M. García; Ortega, Esther; Garcia, R. Dueiias; Granados, A.L. Ortega; Rovira, Pedro Sánchez

doi:10.4321/s0378-48352006000300009

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…The phenothiazine dye, methylene blue (MethyB) is utilized in the treatment of several medical disorders, including methemoglobinemia, cyanide poisoning Clifton and Leikin, (2003), malaria Meissner et al, (2006), and encephalopathy occurring in patients undergoing chemotherapy with ifosfamid (Muñoz, 2006). It is also an effective rescue treatment in vasoplegic shock following cardiac surgery (McCartney et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

The protective effects of methylene blue on thioacetamide-induced acute liver and brain injury

ME Abdel-Salam,

R Youness,

A Morsy

et al. 2023

Drug Dicov

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This study aimed to investigate the potential protective effects of methylene blue (MethyB) on thioacetamide (TAA)-induced acute liver and brain injury in rats.TAA (300 mg/kg) was administrated intraperitoneally (i.p.) with or without MethyB at 10, 20, or 40 mg/kg for two successive days, and rats were euthanized 24 hours after the last treatments. Markers of oxidative stress, including malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide, were determined in liver and brain tissues. Histological examination of liver tissue and different brain regions such as the cerebral cortex, hippocampus, and cerebellum were carried out. Results indicated that compared with the respective saline controls, MDA and nitric oxide levels were significantly raised in the TAA control group, but GSH levels were significantly decreased in the liver and brain tissues. Administration of MethyB to TAA-treated rats resulted in a significant and doserelated decrease in lipid peroxidation (MDA) and nitric oxide. At the same time, the levels of GSH increased in the liver and brain compared with the TAA control group. TAA evoked marked liver tissue damage with micro and macrovesicular steatosis, swelling and apoptosis of hepatocytes, and inflammatory cell aggregates. In addition, TAA caused neuronal cell loss, necrosis, apoptosis of neurons, vacuolar degeneration in cortex and focal gliosis. The hippocampus suffered structural deformity, and shrinkage of large pyramidal cells, with darkened nuclei. In the cerebellum, widely displaced or emptiness of most Purkinje cells, and vacuolation of white matter were observed. MethyB prevented the pathological changes caused by TAA in the brain and liver in a dosedependent manner, with the highest dose of 40 mg/kg providing a remarkable protective effect. The study indicated that MethyB prevented the harmful effects of acutely administered TAA in the liver and brain of rats. These effects of MethyB involved lowered levels of oxidative stress.

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Section: Introductionmentioning

confidence: 99%

The protective effects of methylene blue on thioacetamide-induced acute liver and brain injury

ME Abdel-Salam,

R Youness,

A Morsy

et al. 2023

Drug Dicov

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“…It is also employed in the management of severe sepsis [11], and hypotension that is refractory to vasopressor agents and intravenous fluids [12]. The dye is also an effective remedy for encephalopathy caused by the alkylating agent ifosfamide [13,14]. Recent interest in MethyB focuses on its neuroprotective potential that has been demonstrated in various in vitro and in vivo models of Parkinson's disease [15][16][17], Huntington's disease ROS [18], and Alzheimer's disease [19], and in mitigating neurotoxicity caused by organophosphates [20].…”

Section: Introductionmentioning

confidence: 99%

Methylene Blue Protects against Acidified Sodium Taurocholate-Induced Gastric Mucosal Damage

Abdel-Salam

Sleem

Medhat

et al. 2019

ROS

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The effect of methylene blue (MethyB) on the development of gastric mucosal injury caused by orally given acidified sodium taurocholate (80 mM in 2 ml of 0.15 N HCI) in pylorus-ligated rats was studied. MethyB was intraperitoneally given at doses of 20 and 40 mg/kg at time of pylorus-ligation, and animals were euthanized 90 min later, when gastric secretory responses and the number and severity of mucosal lesions were determined. Lipid peroxidation (malondialdehyde), nitric oxide, reduced glutathione (GSH), and paraoxonase-1 (PON-1) activity in gastric homogenates were measured. Gastric mucosal histopathology and histochemical staining for mucopolysaccharides were also done. Results indicated that acidified sodium taurocholate (Na +taurocholate) caused severe gastric lesions. It also increased gastric malondialdehyde by 70% and decreased GSH levels by 36.4% compared with the corresponding control values. Additionally, nitric oxide decreased by 49.3% and PON-1 activity fell by 54.2% in gastric tissue of Na +-taurocholate-treated rats. The administration of MethyB reduced the number and severity of gastric mucosal lesions but had no effect on gastric acid secretion in Na +-taurocholate-treated rats. MethyB resulted in decreased malondialdehyde and increased GSH, nitric oxide, and PON-1 activity in a dose-dependent manner. Na +-taurocholate caused massive sloughing and hemorrhagic erosions of the superficial parts of gastric epithelium, lamina propria, and sloughing of gastric glands. These changes were markedly attenuated by MethyB at 40 mg/kg. MethyB also restored gastric mucus as indicated by the increase in apical epithelial cells positively stained with periodic acid Schiff. These data suggest a protective effect for MethyB against gastric mucosal damage caused by Na +-taurocholate which is likely to be due to decreased oxidative stress.

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Methylene Blue as a Novel Neuroprotectant in Acute Malathion Intoxication

Abdel-Salam

Youness

Esmail

et al. 2006

ROS

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The effect of methylene blue on oxidative stress and neuronal injury in rats following acute malathion intoxication was examined. Rats were intraperitoneally injected with malathion at 150 mg/kg body weight along with methylene blue at 5 or 10 mg/kg body weight, and euthanized 4 hr later. The levels of lipid peroxidation [malondialdehyde (MDA)], nitric oxide, and reduced glutathione (GSH), and the activities of paraoxonase 1 (PON1), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) were measured in the brain tissue. Histopathological examination and glial fibrillary acidic protein (GFAP) immunostaining were also carried out in this study. Malathion induced a significant elevation in brain lipid peroxidation (MDA) by 32.8% associated with an increased nitric oxide level by 51.4%. Following malathion exposure, brain GSH level fell by 67.7%, and brain AChE and BChE activities decreased by 25% and 60.4%, respectively. Malathion exposure also inhibited PON1 activity by 39.6% and decreased brain glucose level by 30%. Neuronal degeneration in the cortex and hippocampus and strong GFAP immunostaining in the hippocampus were observed in malathion-exposed animals. Methylene blue co-treatment at 10 mg/kg body weight decreased brain MDA by 17.8%, and at 5 and 10 mg/kg body weight, decreased nitric oxide level by 29.2% and 35.8%, respectively. There was no significant effect on the GSH level, but PON1 activity was increased by 22.9%-30.9% upon methylene blue co-treatment. BChE activity did not change but that of AChE increased after cotreatment with the lower dose of methylene blue. Rats receiving methylene blue co-treatment at 10 mg/kg body weight showed no degenerating neurons in the cortex, and occasional degenerating neurons and weak GFAP immunostaining in the hippocampus. Taken together, our results suggest that methylene blue is neuroprotective in acute malathion intoxication, and the neuroprotective effect is likely due to inhibition of oxidative stress and decreased glial cell activation.

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Treatment and prophylaxis of ifosfamide-induced encephalopathy with intravenous methylene blue

Cited by 3 publications

References 6 publications

The protective effects of methylene blue on thioacetamide-induced acute liver and brain injury

The protective effects of methylene blue on thioacetamide-induced acute liver and brain injury

Methylene Blue Protects against Acidified Sodium Taurocholate-Induced Gastric Mucosal Damage

Methylene Blue as a Novel Neuroprotectant in Acute Malathion Intoxication

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