Antinociceptive Effect of Vitamin K2 (Menatetrenone) in Diabetic Mice

Onodera, Kenji; Zushida, Ko; Kamei, Junzo

doi:10.1254/jjp.85.335

Cited by 7 publications

(10 citation statements)

References 10 publications

(13 reference statements)

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“…According to evidence, high oral doses of MK-4 in human (up to 135 mg) [77-79] and in animals (up to 200mg/kg) are effective, safe and have not toxic effects [37,80,81]. Our results showed that MK-4 at the dose of 100 mg/kg/day (similar to other studies [33][34][35]) has no significant effects on mortality rate in experimental group. Thus, we injected 400 mg/kg (200 mg/kg twice in a day i.p.)…”

Section: Discussionsupporting

confidence: 86%

“…At first, the dose of 100 mg/kg MK-4 i.p. was selected due to the previous investigations [33][34][35], however, the mortality rate of ischemic animals was high (equal I/R group). To this reason, we had to enhance the treatment dose to 400 mg/kg in two injections (200 mg/kg i.p.…”

Section: Surgical Procedures For Induction Global Cerebral I/r Modelmentioning

confidence: 99%

“…In order to empirically selection of the neuroprotective administration dose of MK-4 for I/R injury, first, the dose of 100 mg/kg MK-4 i.p. was selected due to the previous investigations [33][34][35]. The findings indicated that the mortality rate of ischemic animals was high (equal to I/R group).…”

Section: Positive Effect Of 400 Mg/kg Mk-4 Administration On Mortalitmentioning

confidence: 99%

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Neuroprotective effect of menaquinone-4 (MK-4) on transient global cerebral ischemia/reperfusion injury in rat

Moghadam

Fereidoni

2020

PLoS ONE

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Cerebral ischemia/reperfusion (I/R) injury causes cognitive deficits, excitotoxicity, neuroinflammation, oxidative stress and brain edema. Vitamin K2 (Menaquinone 4, MK-4) as a potent antioxidant can be a good candidate to ameliorate I/R consequences. This study focused on the neuroprotective effects of MK-4 for cerebral I/R insult in rat's hippocampus. The rat model of cerebral I/R was generated by transient bilateral common carotid artery occlusion for 20 min. Rats were divided into control, I/R, I/R+DMSO (solvent (1% v/ v)) and I/R+MK-4 treated (400 mg/kg, i.p.) groups. Twenty-four hours after I/R injury induction, total brain water content, superoxide dismutase (SOD) activity, nitrate/nitrite concentration and neuronal density were evaluated. In addition to quantify the apoptosis processes, TUNEL staining, as well as expression level of Bax and Bcl2, were assessed. To evaluate astrogliosis and induced neurotoxicity by I/R GFAP and GLT-1 mRNA expression level were quantified. Furthermore, pro-inflammatory cytokines including IL-1β, IL-6 and TNF-α were measured. Seven days post I/R, behavioral analysis to quantify cognitive function, as well as Nissl staining for surviving neuronal evaluation, were conducted. The findings indicated that administration of MK-4 following I/R injury improved anxiety-like behavior, short term and spatial learning and memory impairment induced by I/R. Also, MK-4 was able to diminish the increased total brain water content, apoptotic cell density, Bax/ Bcl2 ratio and GFAP mRNA expression following I/R. In addition, the high level of nitrate/nitrite, IL-6, IL-1β and TNF-α induced by I/R was reduced after MK-4 administration. However, MK-4 promotes the level of SOD activity and GLT-1 mRNA expression in I/R rat model. The findings demonstrated that MK-4 can rescue transient global cerebral I/R consequences via its anti-inflammatory and anti-oxidative stress features. MK-4 administration ameliorates neuroinflammation, neurotoxicity and neuronal cell death processes and leads to neuroprotection. PLOS ONEPLOS ONE | https://doi.org/10.1371/journal.pone.0229769 March 9, 2020 1 / 30 OPEN ACCESS Citation: Farhadi Moghadam B, Fereidoni M (2020) Neuroprotective effect of menaquinone-4 (MK-4) on transient global cerebral ischemia/reperfusion injury in rat. PLoS ONE 15(3): e0229769. https://

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Section: Discussionsupporting

confidence: 86%

Section: Surgical Procedures For Induction Global Cerebral I/r Modelmentioning

confidence: 99%

Section: Positive Effect Of 400 Mg/kg Mk-4 Administration On Mortalitmentioning

confidence: 99%

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Neuroprotective effect of menaquinone-4 (MK-4) on transient global cerebral ischemia/reperfusion injury in rat

Moghadam

Fereidoni

2020

PLoS ONE

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“…CD-1/ICR mice demonstrate thermal allodynia following 7 to 11 days of diabetes [66][67][68][69]. Similarly, allodynia is reported in short term diabetes (2 and 4 weeks) [70,71].…”

Section: Mouse Models Of Dnmentioning

confidence: 70%

Criteria for Creating and Assessing Mouse Models of Diabetic Neuropathy

Sullivan

Lentz²,

Roberts

et al. 2008

CDT

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Diabetic neuropathy (DN) is a serious and debilitating complication of both type 1 and type 2 diabetes. Despite intense research efforts into multiple aspects of this complication, including both vascular and neuronal metabolic derangements, the only treatment remains maintenance of euglycemia. Basic research into the mechanisms responsible for DN relies on using the most appropriate animal model. The advent of genetic manipulation has moved mouse models of human disease to the forefront. The ability to insert or delete genes affected in human patients offers unique insight into disease processes; however, mice are still not humans and difficulties remain in interpreting data derived from these animals. A number of studies have investigated and described DN in mice but it is difficult to compare these studies with each other or with human DN due to experimental differences including background strain, type of diabetes, method of induction and duration of diabetes, animal age and gender. This review describes currently used DN animal models. We followed a standardized diabetes induction protocol and designed and implemented a set of phenotyping parameters to classify the development and severity of DN. By applying standard protocols, we hope to facilitate the comparison and characterization of DN across different background strains in the hope of discovering the most human like model in which to test potential therapies. KeywordsNOD; Akita; ob/ob; db/db; outbred mice; nerve conduction velocity; intraepidermal nerve fiber density DIABETES MELLITUSThe term "diabetes mellitus" describes a number of conditions in which blood glucose is elevated including insulin dependent diabetes mellitus (IDDM) Beyond effective control of glucose levels, there are no treatments to prevent or cure DN. Numerous factors have impeded laboratory investigations aimed at the development of effective therapies, including an incomplete analysis of existing animal models that develop DN, lack of consistency among mouse models (diabetes induction and genetics) and lack of consensus concerning phenotyping methods. The AMDCC was formed by the NIH to develop new animal models of diabetes and its complications; its goal is to identify the most appropriate animal models to study the etiology, prevention and treatment of diabetic complications. The group has reported its findings comparing the effects of diabetes on cardiovascular disease [2], and nephropathy [12] in inbred mice from different genetic background strains and maintains a website containing its recommended phenotyping protocols. AMDCC investigators continue to refine genetic and dietary factors that affect the development of diabetes and its complications, potential interactions and overlap of complications within a genetic model, and common pathways that may influence treatment paradigms in human patients.In order to provide a consistent method of examining DN in diabetic mouse models, our laboratory implemented a standardized diabetes induction protocol used by the AMDCC (...

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“…An underlying vasculitis with ischaemia to peripheral nerves also seemed unlikely, given that he had no cryoglobulins on repeated testing and no cutaneous signs of vasculitis 19. Another possible mechanism may be related to the inhibition of activated vitamin K, even though vitamin K has been associated with widespread physiological benefits,20 including an antinociceptive effect of vitamin K2 in diabetic mice 21. However, a study in PCD 12 animal cells showed vitamin K enhanced nerve growth factor-mediated neurite outgrowth 22.…”

Section: Discussionmentioning

confidence: 99%

Warfarin improves neuropathy in monoclonal gammopathy of undetermined significance

Gomez¹,

Holkova

Noreika

et al. 2016

BMJ Case Reports

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We report a case of a 60-year-old man who was referred to a palliative care clinic with monoclonal gammopathy of undetermined significance (MGUS)-associated neuropathy, responding to a therapeutic trial of warfarin. Electromyography showed distal symmetric sensory axonal neuropathy. The patient reported having had improvement of his neuropathic symptoms while taking warfarin postoperatively for thromboprophylaxis 1 year prior, and recurrence of his symptoms after the warfarin was discontinued. The patient was rechallenged with a trial of warfarin, targeting an international normalised ratio of 1.5-2.0. His pain scores decreased from 5/10 to 3/10 at 1 month and symptom improvement was maintained through 24 months of follow-up. Warfarin had a remarkable impact on our patient's symptoms and quality of life. The mechanisms mediating the symptomatic benefit with warfarin are unclear; however, a placebo effect is unlikely. Further studies may help guide the use of warfarin for MGUS-associated neuropathy.

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Antinociceptive Effect of Vitamin K2 (Menatetrenone) in Diabetic Mice

Cited by 7 publications

References 10 publications

Neuroprotective effect of menaquinone-4 (MK-4) on transient global cerebral ischemia/reperfusion injury in rat

Neuroprotective effect of menaquinone-4 (MK-4) on transient global cerebral ischemia/reperfusion injury in rat

Criteria for Creating and Assessing Mouse Models of Diabetic Neuropathy

Warfarin improves neuropathy in monoclonal gammopathy of undetermined significance

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